– 71 percent of patients treated with upadacitinib achieved the primary endpoint of EASI 75 compared to 61 percent of patients treated with dupilumab at week 16 (p=0.006)[1]

– Upadacitinib showed superiority versus dupilumab for all ranked secondary endpoints, including early improvements in itch and skin clearance[1]

– The Heads Up study evaluated upadacitinib (30 mg, once daily) versus dupilumab (300 mg, every other week) in adults with moderate to severe atopic dermatitis[1]

– The safety profile of upadacitinib was consistent with previous atopic dermatitis studies, with no new safety risks observed[1-3]

– Upadacitinib, a selective and reversible JAK inhibitor discovered and developed by AbbVie, is being studied as a once-daily oral therapy for moderate to severe atopic dermatitis and in several other immune-mediated diseases[1-11]

– Atopic dermatitis is a chronic, relapsing inflammatory condition affecting an estimated 10 percent of adults and 25 percent of adolescents[12-15]

NORTH CHICAGO, IL, USA I December 10, 2020 I AbbVie (NYSE: ABBV) today announced top-line results from the Phase 3b Heads Up study showing that upadacitinib (30 mg, once daily) achieved superiority to dupilumab (300 mg, every other week) for the primary endpoint, the proportion of patients with at least a 75 percent improvement in the Eczema Area Severity Index (EASI 75) at week 16, in adults with moderate to severe atopic dermatitis.1 Of patients treated with upadacitinib, 71 percent achieved EASI 75 at week 16 compared to 61 percent of dupilumab-treated patients (p=0.006).1 Upadacitinib also showed superiority compared to dupilumab for all ranked secondary endpoints, including additional measures of skin clearance and itch reduction.1

The Heads Up study evaluated the efficacy and safety of upadacitinib versus dupilumab in adults with moderate to severe atopic dermatitis who are candidates for systemic therapy.1 Patients were randomized to receive upadacitinib or dupilumab, both as monotherapy treatments, for 24 weeks.1

“As we enter a new era of advanced therapies in atopic dermatitis, head-to-head studies like this will be important to help healthcare providers understand differences in therapies,” said Michael Severino, M.D., vice chairman and president, AbbVie. “These results add to our growing body of evidence for RINVOQ in atopic dermatitis, which is currently under review by health authorities.”

Results of ranked secondary endpoints showed higher efficacy in early improvements of itch and skin clearance in patients treated with upadacitinib compared to patients treated with dupilumab.1 After one week of treatment, the upadacitinib treatment group had a 31 percent reduction in itch (as measured by Worst Pruritus Numerical Rating Scale [NRS]) compared to 9 percent in the dupilumab group (p<0.001).1 Itch improvements were maintained through week 16.1 Additionally, after two weeks of treatment, 44 percent of upadacitinib-treated patients achieved EASI 75 response versus 18 percent of dupilumab-treated patients (p<0.001).1  

Heads Up Results at Week 16*,1
 

Dupilumab (300 mg)

(n=344)

Upadacitinib (30 mg)

(n=348)

EASI 75a 61% 71%
EASI 90b 39% 61%
EASI 100c 8% 28%
Percent Change from
Baseline in Worst
Pruritus NRSd
-49% -67%

Worst Pruritus NRS
Improvement ≥4e

(Dupilumab, n=336)

(Upadacitinib, n=340)

36% 55%
* Primary endpoint was EASI 75 at week 16. Primary endpoint achieved a p-value of 0.006. EASI 90 and EASI 100 at week 16, percent change from baseline in Worst Pruritus NRS at week 16 and improvement in Worst Pruritus NRS ≥4 at week 16 were ranked secondary endpoints. All ranked secondary endpoints achieved p-values of <0.001. Not all ranked secondary endpoints are shown.
a EASI 75 is defined as at least a 75 percent reduction in Eczema Area and Severity Index.
b EASI 90 is defined as at least a 90 percent reduction in Eczema Area and Severity Index.
c EASI 100 is defined as a complete reduction in Eczema Area and Severity Index.
d Defined as percent change from baseline in Worst Pruritus Numerical Rating Scale [NRS].
e Worst Pruritus NRS improvement ≥4 is defined as an improvement (reduction) in Worst Pruritus NRS ≥4. The endpoint was analyzed for participants with pruritus NRS ≥4 at baseline.

The safety profile of upadacitinib was consistent with what was observed in the Phase 3 pivotal studies, Measure Up 1, Measure Up 2 and AD Up.1-3 Through week 16, the most common adverse events were acne for the upadacitinib group and conjunctivitis for the dupilumab group.1 Serious adverse events occurred in 2.9 percent of patients receiving upadacitinib and 1.2 percent of patients receiving dupilumab.1 Serious infections were reported infrequently in both treatment groups (1.1 percent in patients who received upadacitinib and 0.6 percent in patients who received dupilumab).1 One treatment-emergent death due to bronchopneumonia associated with influenza A occurred in a patient who received upadacitinib.1 No malignancies were reported in the upadacitinib group; one non-melanoma skin cancer was reported in the dupilumab group.1 No major adverse cardiac events or venous thromboembolic events were reported in either treatment group.1

Full results from the Heads Up study will be submitted for publication in a peer-reviewed journal. Use of RINVOQ in atopic dermatitis is not approved and its safety and efficacy are under evaluation by regulatory authorities.

About Atopic Dermatitis

Atopic dermatitis is a chronic, relapsing inflammatory condition characterized by a cycle of intense itching and scratching leading to cracked, scaly, oozing skin.12,13 It affects up to an estimated 10 percent of adults and 25 percent of adolescents.13,14 Between 20 and 46 percent of adults with atopic dermatitis have moderate to severe disease.15 The range of symptoms pose significant physical, psychological and economic burden on individuals impacted by the disease.13,16

About Heads Up1

Heads Up is a Phase 3b multicenter, randomized, double-blind, double-dummy, active comparator-controlled study in adults with moderate to severe atopic dermatitis. Patients were randomized to receive upadacitinib (30 mg, once daily, orally administered) or dupilumab (300 mg, every other week, subcutaneous injection) for 24 weeks. Patients who received dupilumab received an initial dose of 600 mg at the baseline visit followed by 300 mg every other week. All patients received placebo of the other arm’s administration as part of the Heads Up double-dummy study design.

The primary endpoint was the proportion of patients achieving EASI 75 at week 16. Ranked secondary endpoints included EASI 75 at week 2, percent change from baseline in Worst Pruritus NRS at week 1 and week 16, EASI 90 at week 16, EASI 100 at week 16 and improvement in Worst Pruritus NRS ≥4 at week 16. More information on this trial can be found at www.clinicaltrials.gov (NCT03738397).

About RINVOQ™ (upadacitinib)

Discovered and developed by AbbVie scientists, RINVOQ is an oral, once daily, selective and reversible JAK inhibitor studied in several immune-mediated inflammatory diseases.1-11 It was engineered to have greater inhibitory potency for JAK1 versus JAK2, JAK3 and TYK2.17 In August 2019, RINVOQ received U.S. Food and Drug Administration approval for adult patients with moderately to severely active rheumatoid arthritis who have had an inadequate response or intolerance to methotrexate. In December 2019, RINVOQ also received approval by the European Commission for the treatment of adult patients with moderate to severe active rheumatoid arthritis who have responded inadequately to, or who are intolerant to one or more disease-modifying anti-rheumatic drugs. The approved dose for RINVOQ in rheumatoid arthritis is 15 mg. Phase 3 trials of RINVOQ in atopic dermatitis, rheumatoid arthritis, psoriatic arthritis, axial spondyloarthritis, Crohn’s disease, ulcerative colitis, giant cell arteritis and Takayasu arteritis are ongoing.1,5-11 Use of RINVOQ in atopic dermatitis is not approved and its safety and efficacy have not been evaluated by regulatory authorities.

Please click here for the Full Prescribing Information and Medication Guide.

Globally, prescribing information varies; refer to the individual country product label for complete information.

About AbbVie

AbbVie’s mission is to discover and deliver innovative medicines that solve serious health issues today and address the medical challenges of tomorrow. We strive to have a remarkable impact on people’s lives across several key therapeutic areas: immunology, oncology, neuroscience, eye care, virology, women’s health and gastroenterology, in addition to products and services across its Allergan Aesthetics portfolio. For more information about AbbVie, please visit us at www.abbvie.com. Follow @abbvie on TwitterFacebook, Instagram, YouTube and LinkedIn.

References:

  1. AbbVie Data on File. ABVRRTI71468.
  2. Guttman-Yassky, E., et al. Safety and Efficacy of Upadacitinib Monotherapy in Adolescents and Adults with Moderate-to-severe Atopic Dermatitis: Results From 2 Pivotal, Phase 3, Randomized, Double-blinded, Monotherapy, Placebo-controlled Studies (Measure Up 1 and Measure Up 2). European Academy of Dermatology and Venerology Congress. 2020. D3T03.4B.
  3. AbbVie Data on File. ABVRRTI70869.
  4. Pipeline – Our Science | AbbVie. AbbVie. 2019. Available at: https://www.abbvie.com/our-science/pipeline.html. Accessed on December 1, 2020.
  5. Burmester G.R., et al. Safety and efficacy of upadacitinib in patients with rheumatoid arthritis and inadequate response to conventional synthetic disease-modifying anti-rheumatic drugs (SELECT-NEXT): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet. 2018 Jun 23;391(10139):2503-2512. doi: 10.1016/S0140-6736(18)31115-2. Epub 2018 Jun 18.
  6. A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study of ABT-494 for the Induction of Symptomatic and Endoscopic Remission in Subjects With Moderately to Severely Active Crohn’s Disease Who Have Inadequately Responded to or 13. Are Intolerant to Immunomodulators or Anti-TNF Therapy. ClinicalTrials.gov. 2020. Available at: https://clinicaltrials.gov/ct2/show/NCT02365649. Accessed on December 1, 2020.
  7. A Study Comparing Upadacitinib (ABT-494) to Placebo and to Adalimumab in Participants With Psoriatic Arthritis Who Have an Inadequate Response to at Least One Non-Biologic Disease Modifying Anti-Rheumatic Drug (SELECT – PsA 1). ClinicalTrials.gov. 2020. Available at: https://clinicaltrials.gov/ct2/show/NCT03104400. Accessed on December 1, 2020.
  8. A Study to Evaluate the Safety and Efficacy of ABT-494 for Induction and Maintenance Therapy in Subjects With Moderately to Severely Active Ulcerative Colitis. ClinicalTrials.gov. 2020. Available at: https://clinicaltrials.gov/ct2/show/NCT02819635. Accessed on December 1, 2020.
  9. A Study to Evaluate Efficacy and Safety of Upadacitinib in Adult Participants With Axial Spondyloarthritis (SELECT AXIS 2). ClinicalTrials.gov. 2020. Available at: https://clinicaltrials.gov/ct2/show/NCT04169373.. Accessed on December 1, 2020.
  10. A Study to Evaluate the Safety and Efficacy of Upadacitinib in Participants With Giant Cell Arteritis (SELECT-GCA). ClinicalTrials.gov. 2020. Available at: https://clinicaltrials.gov/ct2/show/NCT03725202. Accessed on December 1, 2020.
  11. A Study to Evaluate the Efficacy and Safety of Upadacitinib in Subjects With Takayasu Arteritis (SELECT-TAK). ClinicalTrials.gov. 2020. Available at https://clinicaltrials.gov/ct2/show/record/NCT04161898. Accessed on December 1, 2020.
  12. Nutten S. Atopic Dermatitis: Global Epidemiology and Risk Factors. Ann Nutr Metab 2015;66(suppl 1):8–16.
  13. Weidinger, S., et al. Atopic dermatitis. Nat Rev Dis Primers 4, 1 (2018). https://doi.org/10.1038/s41572-018-0001-z.
  14. Eichenfield L.F., et al. Guidelines of care for the management of atopic dermatitis: section 1. Diagnosis and assessment of atopic dermatitis. J Am Acad Dermatol. 2014;70(2):338-351. doi:10.1016/j.jaad.2013.10.010.
  15. Shrestha S., et al. Burden of Atopic Dermatitis in the United States: Analysis of Healthcare Claims Data in the Commercial, Medicare, and Medi-Cal Databases. Adv Ther. 2017;34(8):1989–2006.
  16. EFA. Atopic Eczema: Itching for Life Report. 2018. Available at: https://www.efanet.org/images/2018/EN_-_Itching_for_life_Quality_of_Life_and_costs_for_people_with_severe_atopic_eczema_in_Europe_.pdf. Accessed on October 5, 2020.
  17. Cohen S., et al. Safety profile of upadacitinib in Rheumatoid Arthritis: Integrated analysis from the SELECT Phase 3 Clinical Program. EULAR 2019; THU0167.
  18. RINVOQ™ (upadacitinib) [Package Insert]. North Chicago, Ill.: AbbVie Inc.

SOURCE: AbbVie