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These non-GAAP financial measures are reconciled with comparable GAAP financial measures in our earnings release and regulatory filings from today, which can be found on our website. Following our prepared remarks, we'll take your questions. So with that, I'll turn the call over to Rob.

Robert A. Michael -- President and Chief Operating Officer

Thank you, Liz. Good morning, everyone, and thank you for joining us. Our fourth quarter performance closes out another excellent year for AbbVie, and I'm very pleased with the significant progress we made in 2024. We executed on our top commercial priorities, advanced our pipeline with key regulatory approvals and promising data, and further strengthened our business through strategic transactions.

Turning to our results, we delivered full-year adjusted earnings per share of $10.12, which is $0.49 above our initial guidance midpoint. Excluding the impact of IPR&D expense, total net revenues were $56.3 billion, exceeding our initial guidance by more than $2 billion. Our results demonstrate a rapid return to sales growth, with full-year revenue up 4.6% on an operational basis, despite $5 billion of U.S. Humira erosion in 2024.

This outstanding execution is driven by our ex-Humira platform, which continues to outperform expectations, delivering full-year sales growth of more than 18% with revenue growth accelerating to 22% in the fourth quarter. As I look to 2025 and beyond, we are well-positioned with our ex-Humira platform. It will allow AbbVie to deliver robust mid-single-digit revenue growth in 2025 and exceed our previous peak revenue in just the second year following the U.S. Humira LOE.

And given that we have no significant LOE events for the rest of this decade, we have a clear runway to growth for at least the next eight years, including a high single-digit revenue CAGR through 2029. We anticipate a substantial portion of this growth will be driven by robust performance from Skyrizi and Rinvoq to assets are expected to collectively generate nearly $24 billion of revenue in 2025, reflecting growth of more than $6 billion. Based on this strong momentum, we now expect Skyrizi and Rinvoq to exceed more than $31 billion of combined sales in 2027, which is $4 billion above the guidance we provided last year. We are seeing strong performance across all of their approved indications, especially in IBD.

And we see several tailwinds that will support growth into the next decade, including healthy immunology market growth, strong share capture given best-in-class profiles, continued robust market access, and momentum from new indications, such as the recent launch of Skyrizi in UC, as well as the potential for five new indications for Rinvoq over the next few years. In neuroscience, our second largest therapeutic area, we are seeing very robust performance, with sales of $10 billion expected in 2025, reflecting growth of $1 billion across psychiatry, migraine, and Parkinson's. In oncology, I am very encouraged by our long-term growth prospects. This includes our BCL-2 inhibitor, Venclexta; our FRa ADC for ovarian cancer, Elahere; our two novel c-MET ADCs for solid tumors, Teliso-V and 400, and our BCMA-CD3 bispecific for multiple myeloma 383.

Lastly, while the recent performance in aesthetics has been impacted by challenging market conditions in the U.S. and China, the category remains very attractive given low penetration rates for facial injectables. When the market returns to more normalized growth, our leading commercial portfolio and forthcoming pipeline will help drive improved performance. Based on the market trends over the last few years, and our assumption for a gradual recovery in the near term, we now expect aesthetics to deliver a high single-digit revenue CAGR through 2029.

Turning now to R&D, we have made excellent progress with our late-stage programs. These advancements include recent approvals for Skyrizi in UC, Epkinly in later lines of follicular lymphoma, Elahere for FRa-positive platinum-resistant ovarian cancer, Vyalev for advanced Parkinson's, and new indications for Botox and Juvederm. In 2025, we anticipate approvals for Rinvoq in GCA, and Teliso-V for non-squamous, non-small cell lung cancer, as well as regulatory submissions for Tavapadon in Parkinson's, Venclexta in higher-risk MDS, and BoNT/E for aesthetics. We have also added depth to our pipeline by signing more than 20 early stage deals since the beginning of 2024, including promising technologies and innovative mechanisms that can elevate the standard of care in immunology, oncology, and neuroscience.

We have significant capacity to continue pursuing external innovation with a focus on differentiated opportunities that can drive growth in the next decade. In summary, I am very pleased with AbbVie's execution in 2024. And expect our diverse portfolio to drive strong growth in 2025 and beyond. With that, I'll turn the call over to Jeff for additional comments on our commercial highlights.

Jeff?

Jeffrey Ryan Stewart -- Executive Vice President, Chief Commercial Officer

Thank you, Rob. I'll start with the quarterly results for immunology, which delivered total revenues of approximately $7.3 billion, exceeding our expectations. Skyrizi total sales were nearly $3.8 billion, reflecting operational growth of 57.9%. Rinvoq total sales were more than $1.8 billion, reflecting operational growth of 47.1%.

On a full-year basis, Skyrizi and Rinvoq delivered approximately $17.7 billion in total combined revenue, an impressive increase of nearly $6 billion year over year, exceeding our expectations. These results reflect strong performance across all approved indications. I'll share some highlights in the U.S. Skyrizi total prescription share in the biologic psoriasis market is now approximately 40%, reflecting a very significant lead relative to all major competitors, with in-play capture rates remaining very strong.

Over the course of 2025, we anticipate new data for Skyrizi on hard-to-treat areas of the body, including scalp and genital psoriasis. In addition, we expect the readout of our fifth head-to-head study in psoriasis comparing Skyrizi to Sotyktu, which will continue to differentiate the brand versus oral competitors. Rinvoq is now capturing more than 20% in-place share in atopic dermatitis, as our communication around our level-up study versus Dupixen continues to ramp. Recall that in level-up, we showed strong comparative results on stringent endpoints of skin resolution and itch reduction.

In RA, Rinvoq is achieving the leading in-place share in the second-line plus market, consistent with the brand's label. We see that U.S. physicians are increasingly utilizing only one TNF prior to initiating Rinvoq treatment in RA. In psoriatic arthritis, Skyrizi and Rinvoq together are capturing a leading in-place share in the room category, highlighting the effective co-positioning of both agents in this important segment.

Across IBD, Skyrizi and Rinvoq are also capturing substantial portfolio share, given their respective efficacy, safety, and dosing profiles. In Crohn's disease, which is roughly two-thirds of the overall IBD market, these two treatments together are capturing approximately half of the in-place share with total prescription volumes ramping very rapidly. In ulcerative colitis, we are seeing a very strong inflection following the Skyrizi launch in the second half of last year. Both Skyrizi and Rinvoq together are already capturing roughly a third of the UC in-play market, which supports robust momentum going forward for both AbbVie brands.

We see similar performance internationally as well, where Skyrizi and Rinvoq are also achieving leadership positions across our major countries. So I'm very pleased with this momentum and continue to see a significant opportunity for share gains across our existing indications, in addition to the typical market growth we see across room, derm, and gastro in 2025 and beyond. Turning now to Humira, which delivered global sales of more than $1.6 billion, down 48.7% on an operational basis, primarily due to biosimilar competition, we continue to see molecule compression in the U.S. with volume moving to other novel mechanisms, which has resulted in a benefit to both Skyrizi and Rinvoq.

We anticipate Humira access will decrease throughout 2025 as more plans move to exclusive biosimilar contracts. It's reasonable to assume that roughly half of U.S. covered lives will continue to have parity access to Humira on a full-year basis, with select exclusionary contracts for existing patients expected to begin around the middle of the year. Moving now to oncology, where total revenues were approximately $1.7 billion.

Imbruvica global revenues were $848 million, down 6.2%, reflecting continued competitive dynamics in CLL. Venclexta global sales were $655 million, up 13% on an operational basis, reflecting strong demand for both CLL and AML across our key countries. Lastly, Elahere continues to demonstrate a strong launch trajectory for FR-alpha positive platinum-resistant ovarian cancer, with global sales of $148 million. Sales in the U.S.

are annualizing at more than $600 million and commercialization is now underway in key international markets where we are accelerating regulatory and reimbursement timelines. Moving to neuroscience, where total full-year revenues were $9 billion, reflecting impressive absolute sales growth of nearly $1.3 billion. In the quarter, total revenues were $2.5 billion, up 19.9% on an operational basis. This robust performance is driven by continued double-digit growth of Vraylar with global sales of $924 million, Botox Therapeutic with global revenues of $873 million, Ubrelvy with global sales of $303 million, and Qulipta with global revenues of $201 million.

Beyond these leading therapies for psychiatry and migraine, we are very excited for an emerging portfolio in Parkinson's disease. We recently launched Vyalev, the only subcutaneous 24-hour continuous infusion of levodopa-based therapy for the treatment of advanced Parkinson's disease. As a less invasive, non-surgical delivery system that can provide meaningful improvements in on-time and off-time, we are seeing very high interest from both physicians and patient communities. Parkinson's experts report significant benefit from the continuous 24-hour delivery and the control of symptoms morning, day, and through the night.

While sales in the U.S. are expected to ramp gradually over the next several quarters as we work to establish the appropriate Medicare coverage and benefit determination, uptake internationally is exceeding our expectations. Finally, I'm very encouraged by the data we are seeing for tavapadon for potential use as a monotherapy for early Parkinson's disease, as well as an adjunct to optimize oral therapy for more advanced patients. Tavapadon represents a very complimentary addition to our Parkinson's disease portfolio with Vyalev and Duopa.

So overall, I'm extremely pleased with the commercial execution across our therapeutic portfolio, which is demonstrating very strong momentum as we head into 2025. With that, I'll turn the call over to Carrie for additional comments on aesthetics. Carrie?

Carrie Strom -- Senior Vice President and President, Global Allergan Aesthetics

Thank you, Jeff. Fourth quarter global aesthetic sales were approximately $1.3 billion, reflecting an operational decrease of 4.4%. In the U.S., aesthetic sales of $839 million declined 5% as challenging market conditions and promotional dynamics impacted key assets. Consistent with recent quarters, the U.S.

facial injectable market continues to be affected by suppressed consumer spending that is related to the cumulative impact of high inflation over several years. As a higher price procedure relative to toxins, current conditions are most notably impacting the filler market, which declined by approximately 10% in the quarter. The toxin market remains more resilient, demonstrating low single-digit % growth. Although we continue to be the clear market leader in toxins and fillers, in Q4, our facial injectable share declined by a few points.

In October, we launched an updated version of our Alle consumer loyalty program, which was designed to benefit providers by increasing treatment frequency, patient retention, and cross-selling. While some providers embraced the new loyalty program, many felt the new contract was too complex to integrate into their practices, therefore negatively impacting market share and inventory levels. Based on this market reaction, we reinstated our original Alle consumer loyalty program earlier this month. This action has been met with a rapid and favorable response from our providers with encouraging early indicators for sales and market share recovery.

Internationally, aesthetic sales were $459 million. This represented an operational decline of 3.2% that was primarily due to lower Juvederm sales as Botox cosmetic sales were roughly flat on an operational basis. Our international results were impacted by our second largest global market, China, where lower consumer spending related to economic headwinds continues to affect performance. Looking to 2025, we've planned prudently with our outlook for modest aesthetic sales growth.

In the U.S., this reflects a gradual improvement in market growth rates and share for both toxins and fillers. Additionally, based on our Alle loyalty program changes, we expect a one-time price adjustment to negatively impact our first-quarter U.S. results. Internationally, we are focused on retaining a strong competitive position as we launch multiple new products in China while we closely monitor market conditions and consumer sentiment.

In summary, while economic headwinds and key geographies have created a near-term impact on market conditions, we continue to see significant long-term growth potential, given high consumer interest and low penetration rate. Allergan Aesthetics is uniquely positioned to benefit based on our customer relationships, commercial investments, and innovative pipeline. With that, I'll turn the call over to Roopal.

Roopal Thakkar -- Executive Vice President, Research and Development

Thank you, Carrie. We continue to make significant progress with our R&D efforts to advance novel clinical programs across all stages of our diversified pipeline. In 2025, we expect a strong cadence of important data readouts, regulatory submissions, and new approvals, as well as many clinical trial starts for key programs. Starting with immunology, regulatory applications are under review for Rinvoq and GCA, with approval decisions anticipated in the second quarter.

Data for two phase 3 Rinvoq programs will be available this year, alopecia areata and vitiligo, and for our HS and lupus programs in 2026. Moving to Skyrizi, data from the head-to-head in psoriasis versus Sotyktu will be available this year. Also, this year, to further support differentiation in IBD, a study comparing Skyrizi to Entyvio in ulcerative colitis will be initiated. Additional mid-stage monotherapy and combination studies are planned in 2025, including a phase 2 study evaluating lutikizumab in atopic dermatitis, a phase 2 study evaluating Skyrizi and lutikizumab in psoriatic arthritis, and advancement of our anti-TREM1 antibody, ABBV-8736 with the eventual goal to add it to the Crohn's Disease Platform Study as a monotherapy and in combination with Skyrizi.

Moving to oncology, where multiple regulatory and clinical milestones as well as phase transitions for key programs are planned. One area that we are particularly excited about is our ADC pipeline, where several assets are aimed at multiple tumor types. Our regulatory application is under review for accelerated approval of Teliso-V as a monotherapy in patients with previously treated c-Met overexpressing EGFR wild type non-squamous non-small cell lung cancer. The target for an approval decision is in the first half of this year.

This represents a segment of lung cancer with high unmet need where patients have limited options and tend to have a very poor prognosis. If approved, Teliso-V would be the first c-Met-directed ADC for the treatment of non-small cell lung cancer. We are also rapidly advancing our next-gen c-Met asset. A phase 3 study evaluating ABBV-400, also known as Temab-A, was recently initiated in patients with c-Met overexpressed refractory metastatic colorectal cancer.

Temab-A, as a monotherapy, is being compared against chemotherapy plus bevacizumab. This year, data from a phase 1 CRC study evaluating Temab-A in combination with bevacizumab could enable a phase 3 study in an all-comers population. Temab-A is also progressing well across lung programs. A phase 2 study in EGFR wild-type non-small cell lung cancer is being planned, where Temab-A will be evaluated with a PD-1 inhibitor as a frontline combination therapy.

In the EGFR mutant segment, results from the ongoing phase 1 study could enable Temab-A dose optimization studies as a monotherapy in the second-line setting and in combination with osimertinib in the first-line setting. In gastroesophageal cancer, a phase 2 trial was recently started evaluating Temab-A in combination with chemotherapy and a PD-1 inhibitor in frontline patients. We are also excited about ABBV-706, an ADC that utilizes the same Topo warhead and linker technology as Temab-A, but with an antibody that targets SEZ6. Encouraging data in small lung cancer, small cell lung cancer, were presented at ASCO last year.

And this year, dose optimization and longer-term duration data will be available. This readout could lead to the initiation of a registrational study in second line and dose optimization in combination with standard of care in the frontline. Moving to FRa ADC, Elahere is now approved for platinum resistant ovarian cancer in the U.S. and Europe and is currently in phase 3 development for the platinum sensitive ovarian cancer segment, also, a next-generation ADC targeting FRa, IMGN-151 is currently in phase 1.

This year, Elahere will be tested in combination with bevacizumab and a PARP inhibitor. 151 is being advanced into dose optimization as well as in studies with standard of care agents such as bevacizumab, carboplatin, and a PARP inhibitor. These mid-stage studies for Elahere and 151 will be used to inform our phase 3 approach in various settings for ovarian cancer, including induction and maintenance in platinum sensitive patients and in combination for frontline maintenance. Another ADC from ImmunoGen known as PIVAC targets a rare hematologic malignancy called Blastic Plasmacytoid Dendritic Cell Neoplasm.

Based on positive data from the pivotal phase 2 study, a regulatory application is planned for later this year. If approved, this would be an important new treatment option for patients with this aggressive blood cancer. Also in the area of hematologic oncology, the phase 3 Venclexta MDS study is nearing completion with an overall survival data readout later this year. Now moving to neuroscience, following the Emraclidine EMPOWER-1 and 2 study readouts, a thorough analysis of the data was conducted to better understand the placebo effect observed in the two trials.

Our findings point to a lack of uniformity of placebo effect across sites. When assessing sites beyond those with high placebo response, a clear efficacy signal was observed, albeit more modest than reported in phase 1b. Therefore, we see a path forward as an adjunct to atypicals and schizophrenia and as a monotherapy in psychosis related to Alzheimer's and Parkinson's. These are diseases where there is a high unmet need for safe and tolerable treatments that can provide even a modest benefit.

Additionally, our intention is to explore higher doses of Emraclidine. This is based on the degree of variability observed in the PK data from the EMPOWER studies. If higher doses are found to be safe and well tolerated, there is a potential opportunity to evaluate Emraclidine as a monotherapy in schizophrenia, as higher doses may result in greater efficacy. A multiple ascending dose study will be conducted this year and data will be available in the early part of 2026.

Following this dosing work, phase 2 studies in adjunctive schizophrenia and potentially monotherapy schizophrenia will be initiated. Dose ranging in elderly patients is ongoing with phase 2 studies planned in 2026 in patients with psychosis related to Alzheimer's and Parkinson's Disease. Staying on the topic of Parkinson's Disease, positive top-line results from the third phase 3 trial for Tavapadon were recently announced. In the TEMPO-2 trial, Tavapadon met the primary endpoint, demonstrating a significant reduction in the severity of Parkinson's Disease symptoms compared with placebo at week 26.

Key secondary endpoints were also achieved. We are very pleased with the emerging profile for Tavapadon, which shows strong efficacy as a monotherapy and as an add-on to Levo, Carbidopa. The six-month data from the phase 3 studies show Tavapadon to be generally safe and well tolerated with low rates of adverse events of special interest, such as sedation and impulse control disorder. Longer term safety data will be available this year and regulatory submissions will then follow.

Moving to aesthetics, we met with the FDA late last year regarding our BoNT/E submission for the treatment of glabellar lines. We are in the process of generating additional CMC data requested by the agency, which should be completed in the next few months. The regulatory submission will likely occur around the middle of the year. To summarize, there have been significant advancements across all stages of our pipeline.

In 2025, we anticipate numerous important regulatory and clinical milestones, including many trial starts for key programs. With that, I'll turn the call over to Scott.

Scott Reents -- Executive Vice President, Chief Financial Officer

Thank you, Roopal. Starting with our fourth quarter results, we reported adjusted earnings per share of $2.16 which is $0.08 above our guidance midpoint. These results include an $0.88 unfavorable impact from acquired IPR&D expense. Total net revenues were $15.1 billion reflecting robust growth of 6.1% on an operational basis, excluding a 0.5% unfavorable impact from foreign exchange.

Our ex-Humira platform delivered reported growth of 22%, once again exceeding our expectations. Adjusted gross margin was 83.8% of sales, adjusted R&D expense was 15.1% of sales and adjusted SG&A expense was 23.6% of sales. The adjusted operating margin ratio was 34.7% of sales, which includes a 10.4% unfavorable impact from acquired IPR&D expense. Net interest expense was $610 million.

The adjusted tax rate was 20.2%. Turning to our financial outlook for 2025, our full-year adjusted earnings per share guidance is between $12.12 and $12.32. Please note that this guidance does not include an estimate for acquired IPR&D expense that may be incurred throughout the year. We expect total net revenues of approximately $59 billion reflecting robust operational growth of 5.7% despite a roughly 4% net unfavorable impact across our portfolio from the Medicare Part D benefit redesign.

At current rates, we expect foreign exchange to have a 1% unfavorable impact on full-year sales growth. This revenue forecast contemplates the following approximate assumptions for select key products and therapeutic areas. We expect global immunology sales of $29.4 billion, including Skyrizi revenue of $15.9 billion reflecting growth of more than $4.1 billion driven by continued strong performance in psoriasis as well as robust uptake in IBD; Rinvoq sales of $7.9 billion reflecting growth of nearly $2 billion with continued market growth and share momentum across all approved indications. And Humira total revenue of $5.6 billion, including U.S.

sales of $4 billion as more plans exclude branded Humira around the middle of the year. This forecast includes a $600 million net unfavorable impact from the Medicare Part D benefit redesign. In oncology, we expect global sales of $6.3 billion including IMBRUVICA revenue of $2.7 billion which reflects a $400 million net unfavorable impact from the Medicare Part D benefit redesign; Venclexta sales of $2.6 billion, reflecting continued strong demand, partially offset by a $100 million net unfavorable impact from Medicare Part D benefit redesign and Elahere revenue of $750 million. For Aesthetics, we expect global sales of $5.3 billion reflecting gradual improvement in market conditions across global markets as well as market share recovery in the U.S.

This includes Botox Cosmetic revenue of $2.8 billion and relatively flat sales for Juvederm. For neuroscience, we expect global sales of $10 billion reflecting continued double-digit growth. This includes Vraylar revenue of $3.5 billion reflecting continued strong prescription demand, partially offset by a $200 million net unfavorable impact from the Medicare Part D benefit redesign; Botox Therapeutics sales of $3.5 billion, total oral CGRP revenue of $2.1 billion and Vraylar sales of $300 million. For eye care, we expect global sales of $2.2 billion.

Moving to the P&L for 2025, we are forecasting full-year adjusted gross margin of approximately 84% of sales, adjusted R&D investment of approximately 14.5%, adjusted SG&A expense of approximately $13.2 billion and an adjusted operating margin ratio of roughly 47% of sales. We expect adjusted net interest expense of approximately $2.6 billion which primarily reflects the annualized financing cost for the ImmunoGen and Cerevel transactions. We forecast our non-GAAP tax rate to be approximately 15.6%. Finally, we expect our share count to be roughly flat to 2024.

Turning to the first quarter, we anticipate net revenues of approximately $12.8 billion. At current rates, we expect foreign exchange to have a 1.6% unfavorable impact on sales growth. This revenue forecast comprehends the following approximate assumptions for our key therapeutic areas. Immunology sales of $6.1 billion including Skyrizi sales of $3.2 billion and Rinvoq revenue of $1.6 billion, we expect U.S.

Humira sales of $900 million. We also anticipate oncology revenue of $1.5 billion, aesthetic sales of $1.1 billion which includes an unfavorable one-time price adjustment due to the reimplementation of the original program, neuroscience revenue of $2.1 billion, and eye care sales of $550 million. We are forecasting an operating margin ratio of roughly 44.5% of sales and model a non-GAAP tax rate of approximately 13.8%. We expect adjusted earnings per share between $2.47 and $2.51.

This guidance does not include acquired IPR&D expense that may be incurred in the quarter. Finally, AbbVie's robust business performance continues to support our capital allocation priorities. Our cash balance at the end of December was approximately $5.5 billion and we expect to generate free cash flow approaching $17 billion in 2025, which includes roughly $2.7 billion of Skyrizi royalty payments. This free cash flow will support a strong and growing quarterly dividend, which we have increased by 310% since inception, as well as debt repayment, where we expect to pay down nearly $3 billion of total debt this year and remain on track to achieve a net leverage ratio of two times by the end of 2026.

Our strong cash flow also provides capacity for continued business development to further augment our portfolio. In closing, we are pleased with AbbVie's results in 2024 and our financial outlook remains very strong. We have considerable momentum across our diverse portfolio and we continue to be well-positioned to deliver robust growth in 2025 and beyond. With that, I'll turn the call back over to Liz.

Liz Shea -- Senior Vice President, Investor Relations

Thanks, Scott. [Operator instructions] Operator, first question, please.

Questions & Answers:

Operator

Our first question comes from Vamil Divan with Guggenheim Securities. Your line is open.

Vamil Divan -- Analyst

Great. Thanks for taking the question. So maybe just to dive a little deeper on the Skyrizi, it is a great performance and guidance. Can you just comment a little more on pricing dynamics that you're seeing there as to how you've factored in pricing both for this year and maybe over the next several years? And then, just a quick follow-up on the comments that were given around aesthetics, especially on the share side, I think you lost a few points when maybe getting it back.

Can you just give a sense of where you think the share is now for Botox and Juvederm sort of this point in time? Thank you.

Jeffrey Ryan Stewart -- Executive Vice President, Chief Commercial Officer

Yes, thanks, Vamil. It's Jeff. And I'll comment on Skyrizi and Rinvoq. And I think, we've been very consistent that over the near term and over time, this is a volume-based business, so we're going to see price declines year over year.

But I would say modest, right? We've sort of highlighted that as we negotiate the formularies, we've started to consistently see sort of these low single-digit price concessions. Now, obviously, what Scott highlighted was unique for the 25-year with the Part D redesign that he outlined. So overall, consistent low single-digit price declines from the rebating side with a one-time Part D. And we would anticipate once we left the Part D, we would see that sort of trend going forward.

Robert A. Michael -- President and Chief Operating Officer

And Vamil, this is Rob. I'll just add that if you think about Skyrizi and Rinvoq, our strategy here was to elevate the standard of care for patients and ultimately would drive a rapid return to growth for the company beyond Humira. And that's exactly what we've been able to execute. That strategy has played out.

You see the differentiation in the marketplace. We have nine head-to-head studies. We're launching a few more. We've upgraded our guidance now by an additional $4 billion in 2027.

We've been very consistent in our language around the pricing dynamics. We said when you think about rebates, think about it as negative low single-digits going forward, but given the robust performance of these assets, it's volume that's dominating the growth, and we would expect that to continue.

Carrie Strom -- Senior Vice President and President, Global Allergan Aesthetics

And hi, this is Carrie. I'll answer your question around Botox and Juvederm share. So in the U.S., we remain the clear market leader for both toxins and fillers. In Q4, a few points of share erosion, bringing Botox to around the low to mid-60s, Juvederm to around the low to mid-40s.

As I said, the reversion of the loyalty program back to the original one, which we announced in December. And then, put into action January 21st, was greeted with very positive response from our customers. And encouraging signs for us to recapture that share for both Botox and Juvederm throughout the year. And just to note that the share did not go to one competitor.

Rather, it was more distributed among the entire competitive set.

Liz Shea -- Senior Vice President, Investor Relations

Thanks, Vamil. Operator, next question, please.

Operator

Yes. Our next question comes from Chris Schott with J.P. Morgan. Your line is open.

Chris Schott -- Analyst

Great. Thanks so much. Just a two-parter on the Skyrizi Rinvoq dynamics, maybe just first on the 2027 guidance, can you just elaborate on what were the biggest drivers of upside to those targets, as you think about the various indications for the drugs? I guess, is it fair to think most of this coming from IBD, or is it across the board? And then, probably a longer-term question on those brands, can you just elaborate a little bit more on how we should think about the growth rate beyond 2027? So basically, how mature will these franchises be by then? And what type of growth rates can we think about over time? Thank you.

Jeffrey Ryan Stewart -- Executive Vice President, Chief Commercial Officer

Yes. Maybe -- thanks, Chris. This is Jeff. I'll start on that.

So the primary driver of the change is, in fact, share capture. So the pricing assumptions have been consistent. We can call the markets pretty well. We see the actuals and the long-term trends there.

So it's been really share capture. And I would say that we see it across the board. Certainly, we've been super encouraged with Skyrizi in psoriasis. We continue to see very, very robust TRx share trends.

And there's no question that the ramps in IBD have been very, very significant. So that's a big piece of it. But I would say it's across the board. So predominantly share capture.

I don't know if, Scott, you have anything to add. But that's the big dynamic there on the $4 billion.

Scott Reents -- Executive Vice President, Chief Financial Officer

Yes, Jeff. Maybe, Chris, if it would help, I can give you the breakdown by indication between the two on the 2027 guide, so, we talk about $31 billion combined in 2027. That's our new long-term guidance. That is $11 billion for Rinvoq and $20 billion for Skyrizi.

Rinvoq is broken down. Rheum is about $4.8 billion; dermatology, $2.5 billion; IBD, $3.7. And then, on the Skyrizi side, $12.5 billion of that $20 billion guide is from psoriatic. And the remaining $7.5 billion is coming from IBD.

So that might help you kind of see those where the growth is coming from as well.

Robert A. Michael -- President and Chief Operating Officer

And if we speak to it in terms of the $4 billion, just to give you a sense then, to add to what just Scott mentioned. So Skyrizi is up $3 billion. A billion of that is psoriatic and $2 billion is IBD. We're just seeing tremendous ramps early days with IBD.

And then, for Rinvoq, it's up a billion from the previous guidance. And that's a mix of roughly $300 million rheum, $200 million derm, and $500 million IBD. So again, across the board, we're seeing tremendous performance, particularly in IBD. And then, your question on how to think about the growth, we have obviously given guidance beyond '27.

But as I look at the sell side consensus, clearly the growth that's in sell side consensus beyond '27 is below our expectations. We would expect to see these markets continue to grow. We would also expect to see continued share gains, albeit as you start getting close to that in place share level, the share curve bends, but you still expect to see some level of share growth. And then, keep in mind, we will have the five, we expect the five new indications for Rinvoq, collectively adding about $2 billion in peak sales and so that will also contribute.

So as I think about the rate of growth for Skyrizi and Rinvoq beyond '27, Rinvoq will likely grow faster than Skyrizi because of those new indications, but you'll still see a robust performance from both assets, at least through '32.

Liz Shea -- Senior Vice President, Investor Relations

Thanks, Chris. Operator, next question, please.

Operator

Our next question comes from Geoff Meacham with Citigroup. Your line is open.

Geoff Meacham -- Analyst

Hey, guys. Good morning. Thanks so much for the question. Just had a couple, first one on Cerevel, you guys called out the partial impairment today in the press release.

Just want to get your perspective as to what the drivers are for the remaining value, assuming Tavapadon is mostly it, but wasn't sure what you'd assume for Emraclidine or backup compounds? And then, just on aesthetics, with the new guidance to 2029, is it fair to say that you think '25 could be the trough or have already seen a trough in terms of the growth rate? I'm just trying to think of the longer term picture. And then, just on BoNT/E, I wanted to get your perspective about the potential success there adding new patients to the paradigm, just given the potential there. Thank you.

Robert A. Michael -- President and Chief Operating Officer

Geoff, on your first question regarding -- this is Rob. On your first question regarding Cerevel, so keep in mind, the accounting rules do not allow you to write up an intangible. So even though we are more optimistic about Tavapadon now than we were at the time of the deal, we can't write that value up. So that would be the same as what we originally ascribed.

We still obviously, as Roopal walked you through the development programs for Emraclidine, still see opportunity in adjunctive schizophrenia as well as neuro degenerative psychosis. And we haven't completely given up on the monotherapy opportunity either, but that's a more heavily risk adjusted opportunity now. So when you think about the value you have to take into account, the timing, so there's some level of time delay as well as a different probability of success for monotherapy. That's all baked into because you're essentially valuing risk adjusted revenues.

You have to take that into account. That said, we're still optimistic about the asset. We're pursuing it in these indications. And again, as I mentioned, we haven't completely given up on monotherapy that will depend on dose ranging.

But that is the way we constructed the revaluation of the intangible. But overall, we still see a very nice opportunity particularly for Tavapadon and we still see potential for Emraclidine as well.

Jeffrey Ryan Stewart -- Executive Vice President, Chief Commercial Officer

Geoff, I'll take your question regarding the aesthetics trough. So we've not specifically guided that, but the way that we have modeled it and think about it is we do see recovery. And I think the big headwind here has been over the last two years has been the economic condition. So we do see continued improvement.

Carrie spoke about some of the market growth rates that we're seeing coming back in the U.S. for both fillers and toxins. So we would -- if you model, you would anticipate '25 to be the trough. And then, our long-term guidance is that high-single-digit compound annual growth using '25 as the base year through '29.

And if you model that, that's going to put you somewhere north of $7 billion. Certainly, this is a business we continue to be excited about. We think that there are continuing to be low market penetration rates globally, frankly, and we've got some innovation to continue to drive market growth. That market has grown low-double-digits historically, but I think as we model, we're thinking a high-single-digit growth in the markets.

But we do see some growth accelerators with BoNT/E, and maybe I'll let the team talk about BoNT/E.

Robert A. Michael -- President and Chief Operating Officer

Maybe I'll just mention here just more broadly, this is Rob, on the business. I think as we reflect on the aesthetics performance and we are just going through a period of macroeconomic pressure on that business. But we do continue to see an attractive long-term setup again given low penetration rates, high consumer interest and our leading portfolio, including some exciting pipeline programs in toxins and fillers. When you think about it, as part of AbbVie, the aesthetics business has been able to continue investing despite the macroeconomic challenges and that will allow us to maximize opportunities when the market does recover.

We have set up this business to be a global fully integrated unit with dedicated support from R&D and business development, and I'm confident that focused approach will pay off in the long run. It's just been difficult for us to call the market recovery, but we still have a lot of confidence in the long-term outlook.

Carrie Strom -- Senior Vice President and President, Global Allergan Aesthetics

And this is Carrie. I'll comment on BoNT/E. So as you said, BoNT/E will be an important catalyst for new patient activation into the category. Consideration continues to be very high for aesthetics and for toxins.

And like we said, it continues to be underpenetrated. And that's because there continue to be barriers for these people who are interested in the category, but not acting around cost and concerns of an unnatural look. And that's really where BoNT/E will play an important role based on its unique profile that is suited to address these concerns. It's fast-acting.

It has short duration. So it's going to be a nice option to position for these considerers to try BoNT/E. And then, our commercial strategy will be to convert them from BoNT/E to Botox. So this is going to be an important pipeline catalyst to help us to activate that consumer market and drive more consumers into the toxin category for Botox.

Roopal Thakkar -- Executive Vice President, Research and Development

And it's Roopal. Maybe one comment to add to Carrie's. On the R&D side, even thinking past that, this year we'll initiate a study with BoNT/E plus Botox to cover people immediately and get that long-term benefit. So that, those studies will start this year.

Liz Shea -- Senior Vice President, Investor Relations

Thanks, Geoff. Operator, next question, please.

Operator

Our next question comes from Terence Flynn with Morgan Stanley. Your line is open.

Terence Flynn -- Analyst

Hi. Thanks for taking the questions. You mentioned the net impact of the Part D redesign. Can you tell us what the volume impacts you guys are assuming, if any, in that calculation? And then the second question I had is, on the pipeline slide, you noted you could have some phase 2 UC data for 113, which I believe is your oral NLRX1 agonist.

Just maybe speak to conviction level there and how you think about that on the forward and if that would be something that you could move into phase 3. Thank you.

Scott Reents -- Executive Vice President, Chief Financial Officer

Terence and Scott, I'll take your question on the volume. So we have guided a 4% of a net impact across the business for headwind to growth for Part D redesign. Now, when we think about that volume offset, we've not quantified that in the guidance, but that is part of the 4%. It's a, I would say, in the grand scheme, it's a fairly modest offset overall.

And I think part of what you need to do when you think about that volume, recognize that when you look at the patient segments that exist, there's roughly three patient segments and they each take about a third of the business. But this is really something that will impact the standard eligible, and we're working very hard to ensure that people are electing cap and smooth. And so, we really see that volume offset coming from that one-third of the patient segment to drive that. So that's why I think it's a little bit more of a modest offset, but we've not quantified it.

Robert A. Michael -- President and Chief Operating Officer

And it's logical when you think about it, because the other two-thirds, I mean, you have the LIS population, which is one-third, so they don't have an out-of-pocket burden like the standard eligible do, and the other third are covered by employer plans, where, again, they don't have the same out-of-pocket burden. So when we analyzed it, we looked at the market and saw that about a third, as Scott mentioned, of the population would benefit from the lower out-of-pocket. But keep in mind, the cost share applies to the entire book of Medicare business. That's why the volume doesn't offset the price impact.

Roopal Thakkar -- Executive Vice President, Research and Development

And this is Roopal. I'll cover the NLRX question. This is our asset from Landos. We had observed very early data, I would say phase 1b, in ulcerative colitis, and that looked good, but it was a very small sample size, I would say.

So this will be a robust phase 2 with a placebo comparator, and we'll get objective data from centralized review of endoscopic data. So it will be a good data set to look at, and if it looks good, definitely would be a phase 3 asset for us. And the other consideration we would have, similar to what I highlighted about other biologics that we'd be combining with Skyrizi, if this looks good, this could be a combination agent with Rinvoq as well.

Liz Shea -- Senior Vice President, Investor Relations

Thanks, Terence. Operator, next question, please.

Operator

Yes, our next question comes from Mohit Bansal with Wells Fargo. Your line is open.

Mohit Bansal -- Analyst

Great. Thank you very much for taking my question, and congrats on all the progress, I have a question regarding IMI. So I know you talked in the past about Skyrizi and Rinvoq benefiting from some of the Humira prescriptions going to these agents as well. So taking that aside, it still seems like the volume or IRA space is growing rapidly.

Can you talk a little bit about the underlying dynamics as well here, why this market continues to grow, and how should we think about longer term for the overall market growth itself? Thank you.

Jeffrey Ryan Stewart -- Executive Vice President, Chief Commercial Officer

Yes. So thanks, Mohit. It's Jeff. And like we talked about before, particularly around the acute event, in this case, this was the CDF exclusion in April, we could clearly start to measure the fact that not all of the switching from Humira was going to the biosimilar.

We saw about 20% of it was slipping away into new mechanisms or more advanced mechanisms like Skyrizi and Rinvoq. Now, we've continued to see the molecule compress. And it's just physicians are using just less and less sequentially Humira and the biosimilars over time. I would say it's becoming harder to measure because you're also seeing a lot of dynamics around new head-to-head trials, new indications, new other approaches.

So I would say overall, it's there, but it's relatively modest in the scheme of the volume that is basically accruing from basically the promotion and the profile of the medication. So it should continue. The more that we see sort of disruption in the market, you'll probably continue to see the molecule on trend continue to compress. Now albeit modest, your other point's very important.

These markets are still very, very buoyant and significant. And one of the dynamics that we see over time, and I think we'll begin to see it quite dramatically around the world, particularly in IBD, is that the lines of therapy start to expand. So it used to be like primarily what was fueling the markets was primarily the new patients coming in off of older traditional medications. But now you're seeing the emergence in atopic dermatitis of the second and third-line markets, which are growing quite substantially.

You're going to see that significantly emerge in IBD, whereas before physicians were really, really afraid to move people along. So they did dose intensification, they added more steroids. But now that there's drugs like Skyrizi and Rinvoq and other agents, you're seeing those market lines of therapy expand. And so, that should continue.

And we've contemplated that in our long-term projections. But that gives you some sense of why you're observing what you're seeing.

Robert A. Michael -- President and Chief Operating Officer

Now, as we look across, it's Rob, as we look across the specialty areas, in psoriasis and IBD we're projecting high single-digit market growth. Atopic dermatitis in the mid-teens, it's growing very -- I mean, you're seeing still fairly low penetration rates for atopic dermatitis. So there's tremendous room for growth. So we would anticipate mid-teens market growth there.

And then, in rheumatoid arthritis, that's probably more like low to mid-single digits. But you can see across the board, very nice market growth, which then will be complemented by the market share gains.

Liz Shea -- Senior Vice President, Investor Relations

Thanks, Mohit. Operator, next question, please.

Operator

Yes. The next question comes from Dave Risinger with Leerink Partners. Your line is open.

David Risinger -- Analyst

Yes. Thanks very much. So I have two questions, please. First, regarding ABBV-400 or Temab-A, could you please frame your long-term commercial vision for this candidate, including what some may underappreciate about how broadly it could potentially be adopted in the early 2030s? And then, second, on external transactions, emraclidine was a setback, but AbbVie's overall M&A track record has been very successful.

Could you please discuss your agenda for M&A, including the potential to leverage your franchise strength in related product categories? Thanks so much.

Jeffrey Ryan Stewart -- Executive Vice President, Chief Commercial Officer

Yes. Hi. It's Jeff. So I will give some thoughts on that.

It's a very, very attractive asset. I think it's underappreciated. And part of it is the first category it will compete in, which is colorectal cancer. I mean, if you look at the response rate that we've seen, let's say, in a smaller or mid-size cancer type, which is ovarian cancer with Elahere, it's quite striking.

I mean, Elahere has been the most rapidly adopted ADC in the entire U.S. oncology market. And it's because it entered this market that was basically almost all chemo-based with unmet need where there had been no innovation. And when we look at the entry with 400 or Temab-A into colorectal cancer, it's a substantially larger tumor type, as it's quite evident.

And we've already seen very, very nice monotherapy results in later lines, much, much better than we've seen with the old chemo standard of care. And really, it's whether or not they have c-Met or not. Now, the thing that will really cause a big inflection that Roopal can talk about in a moment is that it's the combinability as you go up into the lines of therapies, OK? And that's really going to make this thing inflect and become a very, very significant product for patients in colorectal cancer over time. Now, the studies will have to bear that out.

And as well, we're seeing very, very significant early results in lung cancer as well. So it is, I think it's an underappreciated asset. We'll have a chance with Teliso-V to sort of set the market around this whole c-Met, the modern c-Met area. But it's quite striking.

So first, we establish in later lines, very big cancer directly against older chemotherapy. And then, we move combination as we move forward. So thanks for the question.

Roopal Thakkar -- Executive Vice President, Research and Development

Hey. It's Roopal, maybe just a comment there on our strategy around ADCs. And I think 400 is a good highlight of that. So we think about what's a good target, meaning high expression on the tumor, low expression in healthy tissue.

And then, we are continuing to focus on patient selection, individualization of care, utilizing robust biomarkers, as Jeff mentioned, c-Met. That is the opportunity to optimize benefit-risk and particularly tolerability. With our Topo Warhead platform, we've seen low rates, for example, of alopecia, stomatitis, diarrhea, which others, I think, continue to struggle with. And safety and tolerability, as Jeff has mentioned, are critical.

So we're also very focused on proper dose optimization to get this right, so we're able to combine in earlier lines. And that's the same approach that we have with the other one I mentioned, 706 in small cell lung cancer and others in the pipeline.

Robert A. Michael -- President and Chief Operating Officer

And then, David, this is Rob. I'll take your question on M&A. And thank you for acknowledging the strong track record we've had as a company. I would agree with that when you think about the transaction with BI that brought us Skyrizi, with Pharmacyclics that brought us Imbruvica, really gave us the critical mass to be a leader in blood cancers, and then the transaction with Allergan, which gave us three verticals that can really drive long-term growth for the company in neuroscience, aesthetics, and eye care.

And then, more recently, the transaction with Immunogen, which really bolstered our ADC pipeline, as Roopal has highlighted. In terms of our go-forward strategy on BD, we continue to pursue assets that can add depth to our pipeline and really drive growth in the next decade. And we have a clear line of sight to growth for at least the next eight years within the company today. And so, my focus is really about bringing in assets that can help drive that growth in the next decade.

And since the beginning of 2024, as I mentioned in my prepared remarks, we've signed more than 20 early stage deals across immunology, oncology, and neuroscience. In immunology, we've added novel mechanisms that have the potential to raise standard care either as a monotherapy or in combination with Skyrizi and Rinvoq. You should expect that strategy to continue. In oncology, we've added new platforms, including multispecifics, trispecifics, T-cell engagers, and in situ CAR-T approaches.

And then within neuroscience, it's not always appreciated the work we've been doing in neuroscience above and beyond cerebral. We expanded our discovery collaboration in psychiatry with Gedeon Richter, who discovered Vraylar. We also invested in a novel mechanism for mood disorders with Gilgamesh. And we recently acquired a next-generation A-beta antibody for Alzheimer's from Aliada.

Again that is our area of focus. We have these five areas that can drive long-term growth. I mentioned neuroscientist aesthetics and eye care, and of course, immunology and oncology. I mean, these are all large markets with high unmet need.

And so, our BD efforts are focused on building pipeline depth in those areas. Now, I should say if we see an opportunity for differentiation in another large market with high unmet need we would consider pursuing it, especially if it can help drive growth in the next decade. And the company has the financial wherewithal to pursue those opportunities as well.

Liz Shea -- Senior Vice President, Investor Relations

Thanks, Dave. Operator, next question, please.

Operator

Yes. Our next question comes from Steve Scala with TD Cowen. And your line is open.

Steve Scala -- Analyst

Thank you so much. I have an observation and two questions. The observation is splitting hairs, but on Part D redesign, the guidance had been a three percentage point headwind. It was just set on the call four percentage points.

A year ago, it was two percentage points. If there is a change, please, can you identify that? Related to that is my first question. Are you seeing any evidence that IRA Medicare pricing is spilling over to the commercial market? And if yes, to what degree, or is there absolutely none? And then, my second question, the company has provided a lot of helpful perspective on the aesthetics market, but can you distill it to a number? The guidance for aesthetics was previously greater than $9 billion in 2030. What is that number now? Thank you.

Scott Reents -- Executive Vice President, Chief Financial Officer

Steve, this is Scott. I'll go ahead and start with your Part D observation and question. With Part D, we really -- we saw that as something that the analysts and maybe the marketplace hadn't fully understood the impact. I think we were one of the first companies to come out and talk with any sort of specificity and granularity around what we saw that Part D impact, mechanics of how it would work, and the impact to it.

So we came out with a guidance number, and I think that has probably, as you noted, the numbers, but it's evolved a little bit over time. I would say it's evolved not necessarily from our understanding of Part D, but because really the mix of the business. So when we talk about it in the second quarter, I believe I came out and said we saw it would see an approximately 3% headwind to growth from the Part D redesign. We've distilled that number and made a precise number of 4%, roughly 4% today.

And really, when you think about when I came out with that 3%, we've seen momentum in the business, and we've seen momentum in the business in areas, immunology and oncology in particular, where we reached some guidance, where we saw have high Part D channel mix. And so, that's really been a business mix change that has led to that 4% change, and that's really kind of what it's amounted to.

Robert A. Michael -- President and Chief Operating Officer

And Steve, I'll just add, I mean, when you think about the setup for the company, in '25, we said we would return to robust growth, and we're delivering in absolute terms in our guidance a little bit more than $2.5 billion of growth, and that's with headwinds from U.S. Humira erosion around $3 billion, the Part D benefit redesign of approximately $2 billion when you do the math on the roughly 4%, and then a $500 million headwind from the stronger U.S. dollar. So the underlying growth platform is going to drive $8 billion of growth when you think about Skyrizi and Rinvoq, as well as neuroscience.

So the change you're seeing from, as Scott mentioned, is really more of a function of mix, but we're very pleased with the underlying growth that the business has allowed us to absorb these impacts and still deliver robust growth in 2025.

Jeffrey Ryan Stewart -- Executive Vice President, Chief Commercial Officer

Steve, it's Jeff. I'll take your second question. So as we've negotiated across the commercial books and the Medicare books, we have not seen any spillover or slippage in our actual negotiations over the last cycles. And one thing I would add is that we have seen in '24 some more consumption on the benefit redesign, particularly in our oncology agents.

So for Imbruvica and Venclexta, we actually see lower discontinuations and some more consumption. And so, that's encouraging, because if you remember that Part D sort of had the lead in where the cap moved down to roughly $33,000, $34,000, it'll sequentially move down more to $2,000 with the smoothing next year, which is a good policy, because it's encouraging to see that the change in benefit design makes people stay on their cancer medication a bit longer. Again, the volume will be more modest than the price hit, as Rob and Scott described it. But that's the dynamics that we're seeing in the channels.

Scott Reents -- Executive Vice President, Chief Financial Officer

And to answer your question regarding the aesthetics guidance, I'll reinforce maybe what I said earlier and Rob as well. So when we look at that guidance, that long-term guidance is calling for high single-digit CAGR '25 through '29, so using '25 as the base here. If you do the math on that range, that is something above $7 billion, a little bit north of $7 billion, depending on where it falls within that high single-digit range. So that's why we've specifically given the range on the high single-digit.

The market growth that we've seen historically has been low double-digits, but we're seeing that market we're modeling for now, high single-digit growth during the time period that we've given this long-term guidance. And so, I think that answers your specific questions.

Steve Scala -- Analyst

Thank you very much.

Liz Shea -- Senior Vice President, Investor Relations

Thanks, Steve. Operator, next question, please.

Operator

The next question comes from Tim Anderson with Bank of America. Your line is open.

Tim Anderson -- Bank of America Merrill Lynch -- Analyst

Thank you. A couple of questions, please. On aesthetics, a question I've asked before, what are your expectations for how obesity drugs are going to impact this business? You could argue that the surge in use of products, the GRIP ones, could be either a tailwind or a headwind to the use of products like toxins and fillers. It could be a headwind if patients are having to pick and choose between which products to put their out-of-pocket dollars toward.

And then, a second question unrelated to the first. PBM reform still being debated in Washington. If AbbVie had its way, what would change about the current relationship between PBMs and drug companies, and what would you argue should be left alone?

Carrie Strom -- Senior Vice President and President, Global Allergan Aesthetics

Hi. This is Carrie. I'll answer your first question around the obesity market and the aesthetics opportunity. And you're exactly right.

It continues to be both a headwind and a tailwind, a headwind in terms of share of wallet as these consumers are making decisions on what they're going to spend for. We see that more for the higher-priced products like fillers. And then, also a tailwind as this gets a new group of consumers or patients interested in aesthetics, and many of our aesthetic providers are administering these products. And so, they see this as an opportunity for lead generation and bringing new patients into the category.

So we do see it as both a tailwind, a headwind in the short term, but a tailwind in the long term. And the question is not if injectables work. We know that these products work well in these patients. It's really about how we can partner with our customers to build it and integrate it into their treatment practice.

And that's what we're doing with our customers now in helping them position Botox and Juvederm in our product line for these new patients that are entering their practice.

Robert A. Michael -- President and Chief Operating Officer

And Tim, this is Rob. I'll take your question on PBM reform. Look, if there are changes to the rebate system, we don't have a strong preference between rebates or discounts. And that's because we've always competed on the attributes of our products, both the clinical benefit they provide and the value they return to health systems.

So we're confident in our ability to compete in either world. I would just point to our share performance in international markets that do not have a rebate-based system. And we see similar market shares in those countries as well. So we can compete effectively in either system.

We don't have a preference.

Liz Shea -- Senior Vice President, Investor Relations

Thanks, Tim. Operator, next question, please.

Operator

Our next question comes from Chris Raymond with Piper Sandler. Your line is open.

Christopher Raymond -- Analyst

Yes, thanks. Just a question on atopic derm as a target indication, just from some of our work, it looks like the upside we're seeing in Rinvoq is largely in room and gastro. And I know you guys have sort of mentioned this, and it's fairly well-known. But in atopic derm, at least from our data, it looks like things are starting to flatten out a little bit.

And I heard your comments on the derm share of Rinvoq revenue in 2027. But that would seem to infer maybe some kind of inflection. So maybe a two-part question here; first, talk about the current maybe atopic derm growth dynamic, and is there an inflection sort of anticipated? And then the second part of that is, should we be paying more attention maybe to lutikizumab as a contributor here? I know, Jeff, you've talked about atopic derm as a very important indication that you guys are targeting. Or is there some other sort of area, like external innovation, that you think will augment maybe your position in this indication? Thanks.

Jeffrey Ryan Stewart -- Executive Vice President, Chief Commercial Officer

Yeah. It's a very good question. It's an important segment. And to give you some sense of what we see in terms of the inflection.

So we have seen a significant inflection in our new patient capture. And this is despite the launch of other interleukin products over the last year. So we've ramped to the highest in-place shares that we've had. And it was largely flat in the teens for mid-teens for many, many quarters.

And it's ramping up now above 20%. And a lot of that is we've been able to start to distinguish Rinvoq on these stringent endpoints. Basically, like really minimal disease activity where you're taking itch down to a very, very low level. And you're almost completely clearing the skin.

And those are the endpoints where we significantly outperform DUPI. Now, having said that, DUPI's still got the vast majority there, but we are seeing, we will see that in-place shares start to build into the TRXs over time, because our TRX share is quite below 20% at that point. I think the other thing that I'd note is that in many, or if not most, of the outside the U.S. markets, our shares are much higher and building even a little bit faster.

So in several large markets, we actually are ahead of Dupixent. And some of that has to do with the way that the label worked during our initial launch, etc. But we're quite bullish over time in terms of Rinvoq as this is the best agent in terms of getting to the complete control. Now, having said that, we would and we will continue to look for more assets.

Some are in our pipeline as described. But this is a very, very attractive space that we want to continue to invest in. I don't know, Roopal, if you've got any comments on ludi or some of the other concepts.

Roopal Thakkar -- Executive Vice President, Research and Development

That's right. I mean, with the 5% penetration rate, there's still many patients that are untreated. So lutikizumab will be our next one. And Jeff mentioned, there's other pipeline assets that we're working on.

And key being skin clearance along with that itch. And if you can get them both and have a safe and tolerable profile, I think that'll continue to be competitive.

Liz Shea -- Senior Vice President, Investor Relations

Thanks, Chris.

Christopher Raymond -- Analyst

Thank you.

Liz Shea -- Senior Vice President, Investor Relations

Operator, next question, please.

Operator

Thanks. Our next question comes from Trung Huynh with UBS. Your line is open.

Trung Huynh -- UBS -- Analyst

Great. Thanks for taking my questions. Just two for me, so, firstly, your sales in 4Q, did you see any notable difference in trends in stocking or gross-to-net patterns across the portfolio ahead of the changes in Part D versus previous years? Specifically, I'm interested if you had any meaningful one-offs for Skyrizi and Rinvoq for the quarter. And then, circling back on aesthetics, thanks for that updated long-term guide, can you give us a bit more color geographically how we should think about the split between ex-U.S.? China versus the U.S.

as you return to growth? Is there an expectation on one coming back quicker than the other? Thanks.

Scott Reents -- Executive Vice President, Chief Financial Officer

This is Scott. I'll talk about the stocking. So we did not see -- in the past, we've talked about it a couple years ago in particular. But the stocking was relatively minimal from in terms of the impact.

So we did not see anything with respect to Skyrizi and Rinvoq on the stocking in the fourth quarter that'll be impacted in the first quarter.

Trung Huynh -- UBS -- Analyst

And no real dynamics around gross to net either?

Scott Reents -- Executive Vice President, Chief Financial Officer

No, that's right. For Skyrizi and Rinvoq, I'm sorry, no dynamics around gross to net for Skyrizi and Rinvoq. And with respect to aesthetics, I don't know Carrie if you want?

Carrie Strom -- Senior Vice President and President, Global Allergan Aesthetics

Sure. For aesthetics, if we think about the long-term, we see, like we said, we're planning prudently for the economic recovery around key markets like U.S. and China, where it's been challenging for the past few years. Both those markets will continue to be important moving forward as will the rest of the world.

We see Japan as posting nice growth as being an underdeveloped market that we're able to invest in. And then, the pipeline catalysts will be important in both U.S. and the rest of the world. Notably, in China, in the past year, we've had multiple new pipeline catalysts, which are going to -- which continue to help drive share for both toxins and fillers last year and this year.

And we expect the international business to continue to increase as a percent of the revenue for overall global Allergan aesthetics.

Liz Shea -- Senior Vice President, Investor Relations

Thanks, Trung. Operator, we have time for one final question, please.

Operator

Sure. And our last question comes from Chris Shibutani with Goldman Sachs. Your line is open.

Chris Shibutani -- Analyst

Great. Thank you very much. When you think about going beyond 2030 with your strategy across the portfolio, can you comment about the potential impact of some of these combination approaches in immunology? Do you expect these to be IP extending? Will there be co-formulation based approaches, just trying to understand the potential revenue implications, noting that clearly there could be some clinical benefit that could certainly make sense. And then, just a question about a business segment that has been around that you never talk about, which is eye care, how and why does this fit going forward? I understand there's a legacy with the Allergan deal.

But just trying to think about the overall portfolio in areas where you clearly have strengths, but this seems to be one which is less than 5% of revenues. But what is the role for that on the board? How are you thinking about it? Thank you.

Roopal Thakkar -- Executive Vice President, Research and Development

Hey, Chris. It's Roopal. Maybe I'll start the ball rolling here on how we think about combos into '23 -- sorry in the 2030. So the first thing is we have a very strong foundational asset in particularly IBD with Skyrizi.

And you've heard me mention other combo studies in the psoriatic arthritis today as well. Now, that we would combine with the multiple assets that we've mentioned over time; TL1A, TREM-1, alpha 4 beta 7, IL-1 alpha beta, lutikizumab that we already have, that we would be able to look at as monotherapies and combo therapies. If they look good as monotherapies, they could also move forward by themselves. For all of these assets, we're also looking at biomarker approaches.

Particularly with lutikizumab, but we would apply that same strategy to all of these assets. And as combinations, the goal would be co-formulations. So as we enter into the clinical study, we're also doing CMC work in parallel to facilitate combination, co-formulation approaches. So that would also be a convenience factor.

And we would want to match with longer-acting agents. So for example, the TL1A we believe to be a longer acting agent. For TREM-1 we're seeing a long pharmacodynamic effect as an example. But then, the next way that we think about this, these combo strategies, is if we start seeing utility there, obviously moving forward with the co-formulation, but we are very competent in making bi-specifics.

Lutikizumab is one of those. So then in parallel we're making bi-specifics that could then also stand alone as single assets. And then, as you've heard recently with our Nimble transaction, we would also be looking at different mechanisms as an oral peptide. The lead one being IL-23, but we're also working on a TL1A.

And what's unique and what we like about that platform is the potency, potentially being able to reduce the amount of peptide that's required and these assets having long half-lives. So if that holds, then you could imagine combinations as a pill with these peptides with that type of profile that we hope to see. So multiple steps as we think about immunology.

Robert A. Michael -- President and Chief Operating Officer

This is Rob. Your question on eye care, I mean our focus on eye care is in glaucoma, retinal disease, and prescription dry eye. We like that business. It precipitates in a large market with high unmet need, meets that criteria.

It has very much a scientific focus. It's a data-driven business. It's a very efficient business as well. And obviously, we're excited about the REGENXBIO Gene Therapy Program focused on wet AMD and diabetic retinopathy.

Depending on how that plays out, I think you could see that as becoming a stronger growth driver. We obviously have four of the five, as you think about, you get a lot of questions there. But we don't get as many questions on eye care, but we do believe as you start to get more visibility to this REGENXBIO Program, you'll likely spend more time focusing on it. We think of it as a potential to be a long-term growth driver for the company.

And we like the fit it has for AbbVie.

Liz Shea -- Senior Vice President, Investor Relations

Thank you, Chris. And that concludes today's conference call. If you'd like to listen to a replay of the call, please visit our website at investors.abbvie.com. Thanks again for joining us.

Operator

[Operator signoff]

Duration: 0 minutes

Call participants:

Liz Shea -- Senior Vice President, Investor Relations

Robert A. Michael -- President and Chief Operating Officer

Jeffrey Ryan Stewart -- Executive Vice President, Chief Commercial Officer

Carrie Strom -- Senior Vice President and President, Global Allergan Aesthetics

Roopal Thakkar -- Executive Vice President, Research and Development

Scott Reents -- Executive Vice President, Chief Financial Officer

Vamil Divan -- Analyst

Jeff Stewart -- Executive Vice President, Chief Commercial Officer

Rob Michael -- President and Chief Operating Officer

Chris Schott -- Analyst

Geoff Meacham -- Analyst

Terence Flynn -- Analyst

Mohit Bansal -- Analyst

David Risinger -- Analyst

Steve Scala -- Analyst

Tim Anderson -- Bank of America Merrill Lynch -- Analyst

Christopher Raymond -- Analyst

Chris Raymond -- Analyst

Trung Huynh -- UBS -- Analyst

Chris Shibutani -- Analyst

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AbbVie (ABBV) Q4 2024 Earnings Call Transcript was originally published by The Motley Fool