AbbVie's Upadacitinib Shows Significant Improvements in Physical Function, Pain and Quality of Life as a Monotherapy in Patients with Rheumatoid Arthritis in Phase 3 Patient-Reported Outcomes Data

NORTH CHICAGO, Ill., Oct. 23, 2018 /PRNewswire/ -- AbbVie (NYSE: ABBV), a research-based global biopharmaceutical company, today announced new patient-reported outcomes data from the ongoing Phase 3 SELECT-MONOTHERAPY trial evaluating upadacitinib (15 mg and 30 mg, once-daily), an investigational JAK1-selective inhibitor, as a monotherapy treatment in patients with moderate to severe rheumatoid arthritis who did not adequately respond to treatment with methotrexate.¹ Improvements in physical function, health-related quality of life, pain and morning joint stiffness were reported after 14 weeks of treatment with upadacitinib monotherapy compared to patients continuing methotrexate.¹ These results will be presented at the 2018 American College of Rheumatology (ACR)/Association for Rheumatology Health Professionals (ARHP) Annual Meeting in Chicago.

AbbVie has previously announced positive top-line results from SELECT-MONOTHERAPY.

"Upadacitinib as a monotherapy showed significant improvements in rheumatoid arthritis patients' ability to perform daily activities and overall health-related quality of life," said Marek Honczarenko, M.D., Ph.D., vice president, global immunology development, AbbVie. "These results show that the improvements in clinical symptoms are accompanied by improvement in outcomes important to patients. These results reinforce upadacitinib's therapeutic potential across diverse rheumatoid arthritis patient populations and its use as a monotherapy treatment option."

Patient-reported outcome results from SELECT-MONOTHERAPY are as follows:

Physical Function¹

• Improvements in physical function, as measured by the Health Assessment Questionnaire-Disability Index (HAQ-DI), were observed as early as two weeks after initial treatment with upadacitinib across both doses compared to eight weeks for patients receiving methotrexate. At week 14, 65/69 percent of patients receiving 15/30 mg of upadacitinib reported improvements in physical function (HAQ-DI) compared with 45 percent of patients receiving methotrexate (p<0.001).

Health-related Quality of Life¹

• At week 14, 65/73 percent of patients receiving 15/30 mg of upadacitinib reported improvements in health-related quality of life (physical component score of Short Form 36 Health Survey) compared with 48 percent of patients receiving methotrexate (p<0.001).

Joint Pain¹

• Patients reported reductions in pain, as measured by the Patient's Assessment of Pain (based on Visual Analog Scale [VAS]), as early as two weeks after initial treatment with both doses of upadacitinib compared to four weeks for patients receiving methotrexate. At week 14, 64/75 percent of patients receiving 15/30 mg of upadacitinib reported a reduction in pain compared with 46 percent of patients receiving methotrexate (p<0.001).

Morning Stiffness¹

• Patients receiving upadacitinib reported reductions in the severity of morning stiffness as early as two weeks after initial treatment with both doses of upadacitinib compared to four weeks for patients receiving methotrexate. At week 14, 27/28 percent of patients receiving 15/30 mg of upadacitinib reported reductions in the severity of morning joint stiffness compared to 18 percent of patients receiving methotrexate (p<0.001). Additionally, patients treated with both 15/30 mg of upadacitinib had a mean reduction of 95/102 minutes in the duration of morning stiffness compared to 53 minutes with methotrexate (p<0.05) at week 14.

"Upadacitinib significantly improved physical function, joint pain and morning stiffness in addition to health-related quality of life as an oral, monotherapy treatment in this trial," said Vibeke Strand, M.D., adjunct clinical professor in the Division of Immunology/Rheumatology at Stanford University and lead investigator in the studies. "These results are especially important because many patients cannot tolerate or do not respond to treatment with methotrexate and additional effective monotherapy options are needed for these patients."

Results from a separate, exploratory analysis evaluating the association between patient-reported outcomes and clinical outcomes will be presented at ACR and show that achieving substantial improvements in pain, physical function and fatigue were associated both with individual physician-derived measures and with composite disease outcomes such as ACR20/50/70, clinical remission and low disease activity.¹⁰ The analysis demonstrated how the use of patient-reported outcomes in clinical trials provides critical insight into the impact of rheumatoid arthritis on patients.¹⁰ The analysis included a diverse patient population with difficult-to-treat disease, refractory to biologics and conventional synthetic DMARDs, such as methotrexate, who were enrolled in the Phase 3 SELECT-NEXT, SELECT-BEYOND (both studies with background csDMARDs) and SELECT-MONOTHERAPY clinical trials.¹⁰

Rheumatoid arthritis, which affects an estimated 23.7 million people worldwide, is a chronic and debilitating disease.¹¹ Many patients do not respond to or cannot tolerate methotrexate, a commonly used first-line therapy.^12-14 Increasingly, patient-reported outcomes are being included in randomized clinical trials in order to understand how rheumatoid arthritis patients perceive the physical, psychological and social impact of their disease.¹⁵ Using patient-reported outcomes data to assess the impact of disease provides valuable insights to healthcare providers.¹⁵

Safety results from SELECT-MONOTHERAPY have been previously reported here.

About SELECT-MONOTHERAPY⁴

SELECT-MONOTHERAPY is a Phase 3, multicenter, randomized, double-blind, parallel-group study designed to evaluate the safety and efficacy of upadacitinib monotherapy in adult patients with moderate to severe rheumatoid arthritis and an inadequate response to a stable dose of methotrexate. Patients were randomized to switch from methotrexate to upadacitinib monotherapy (15 mg or 30 mg once-daily) or continue on their prior stable dose of methotrexate in a blinded manner. The primary endpoints of the first phase included the percentage of subjects achieving an ACR20 response and low disease activity (LDA) after 14 weeks of treatment. Secondary endpoints included proportion of patients achieving ACR50, ACR70 and clinical remission at week 14, HAQ-DI, duration of morning (AM) stiffness and health-related quality of life (QoL) by SF-36. The trial is ongoing and the second phase is a blinded long-term extension period to evaluate the long-term safety, tolerability, and efficacy of the two once-daily doses (15 mg and 30 mg) of upadacitinib monotherapy in patients who have completed the first phase. More information on this trial can be found at www.clinicaltrials.gov (NCT02706951).

About the SELECT Study Program

The robust SELECT Phase 3 rheumatoid arthritis program evaluates more than 4,000 patients with moderate to severe rheumatoid arthritis in six studies. The studies include assessments of efficacy, safety and tolerability across multiple rheumatoid arthritis patient populations. Key measures of efficacy evaluated include ACR responses, Disease Activity Score (DAS28-CRP) and inhibition of radiographic progression. More information on these trials can be found at www.clinicaltrials.gov (NCT02706847, NCT03086343, NCT02629159, NCT02706873, NCT02706951, NCT02675426).

About Upadacitinib

Discovered and developed by AbbVie, upadacitinib is a once-daily oral, small molecule JAK1-selective inhibitor being developed for moderate to severe rheumatoid arthritis and other immune-mediated diseases.^2,3 Phase 3 trials of upadacitinib in psoriatic arthritis, Crohn's disease and atopic dermatitis are ongoing and it is also being investigated to treat ulcerative colitis and ankylosing spondylitis.^4-9

Upadacitinib is an investigational oral agent and is not approved by regulatory authorities. Safety and efficacy have not been established.

About AbbVie

AbbVie is a global, research and development-based biopharmaceutical company committed to developing innovative advanced therapies for some of the world's most complex and critical conditions. The company's mission is to use its expertise, dedicated people and unique approach to innovation to markedly improve treatments across four primary therapeutic areas: immunology, oncology, virology and neuroscience. In more than 75 countries, AbbVie employees are working every day to advance health solutions for people around the world. For more information about AbbVie, please visit us at www.abbvie.com. Follow @abbvie on Twitter, Facebook, LinkedIn or Instagram.

Forward-Looking Statements

Some statements in this news release are, or may be considered, forward-looking statements for purposes of the Private Securities Litigation Reform Act of 1995. The words "believe," "expect," "anticipate," "project" and similar expressions, among others, generally identify forward-looking statements. AbbVie cautions that these forward-looking statements are subject to risks and uncertainties that may cause actual results to differ materially from those indicated in the forward-looking statements. Such risks and uncertainties include, but are not limited to, challenges to intellectual property, competition from other products, difficulties inherent in the research and development process, adverse litigation or government action, and changes to laws and regulations applicable to our industry. Additional information about the economic, competitive, governmental, technological and other factors that may affect AbbVie's operations is set forth in Item 1A, "Risk Factors," of AbbVie's 2017 Annual Report on Form 10-K, which has been filed with the Securities and Exchange Commission. AbbVie undertakes no obligation to release publicly any revisions to forward-looking statements as a result of subsequent events or developments, except as required by law.

References:

1. Strand, V. et al. Abstract #2547. 2018 ACR/ARHP Annual Meeting. October 2018.
2. Voss, J, et al; Pharmacodynamics Of a Novel Jak1 Selective Inhibitor In Rat Arthritis and Anemia Models and In Healthy Human Subjects. [abstract]. Arthritis Rheum 2013;65 Suppl 10 :2374. DOI: 10.1002/art.2013.65.issue-s10.
3. Pipeline – Our Science | AbbVie. AbbVie. 2018. Available at: https://www.abbvie.com/our-science/pipeline.html. Accessed on September 27, 2018.
4. Smolen, J. et al. Abstract #889. 2018 ACR/ARHP Annual Meeting. October 2018.
5. 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. 2018. Available at: https://clinicaltrials.gov/ct2/show/NCT03104400. Accessed on September 27, 2018.
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 Are Intolerant to Immunomodulators or Anti-TNF Therapy. ClinicalTrials.gov. 2018. Available at: https://clinicaltrials.gov/ct2/show/NCT02365649. Accessed on September 27, 2018.
7. A Study Evaluating the Safety and Efficacy of Upadacitinib in Subjects With Active Ankylosing Spondylitis (SELECT Axis 1). ClinicalTrials.gov. 2018. Available at: https://clinicaltrials.gov/ct2/show/study/NCT03178487. Accessed on September 27, 2018.
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. 2018. Available at: https://clinicaltrials.gov/ct2/show/NCT02819635. Accessed on September 27, 2018.
9. Evaluation of Upadacitinib in Adolescent and Adult Patients With Moderate to Severe Atopic Dermatitis (Eczema)- Measure Up 1. ClinicalTrials.gov. 2018. Available at: https://clinicaltrials.gov/ct2/show/NCT03569293?cond=Atopic+Dermatitis&intr=upadacitinib&phase=2&rank=1. Accessed on September 27, 2018.
10. Strand, V. et al. Abstract #2546. 2018 ACR/ARHP Annual Meeting. October 2018.
11. World Health Organization. The Global Burden of Disease, 2004 Update. Available at: http://www.who.int/healthinfo/global_burden_disease/GBD_report_2004update_full.pdf. Accessed on September 27, 2018.
12. Shinde, CG, Venkatesh, MP, Pramod Kumar, TM, Shivakumar, HG. J Pain Palliat Care Pharmacother. 2014 Dec;28(4):351-8. doi: 10.3109/15360288.2014.959238. Epub 2014 Oct 16.
13. Swierkot J and Szechinski J. Methotrexate in rheumatoid arthritis. Pharmacol Rep. 20116 Jul-Aug;58(4)473-92.
14. Fautrel B, Nab HW, et al. Identifying patients with rheumatoid arthritis with moderate disease activity at risk of significant radiographic progression despite methotrexate treatment. RMD Open. 2015; 1(1). DOI: 10.1136/rmdopen-2014-000018.
15. Deshpande, P.R. et al. Patient-reported outcomes: A new era in clinical research. Perspect Clin Res. 2011 Oct-Dec; 2(4): 137–144.

SOURCE AbbVie

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