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NORTH CHICAGO, Ill., June 12, 2018 /PRNewswire/ -- AbbVie (NYSE: ABBV), a research-based global biopharmaceutical company, today presented new patient-reported outcome data during the Annual European Congress of Rheumatology (EULAR 2018) in Amsterdam from three Phase 3 trials evaluating upadacitinib, an investigational, once-daily oral JAK1-selective inhibitor, in adult patients with moderate to severe rheumatoid arthritis.^1,2,3 Improvements in pain, physical function and morning joint stiffness were reported after 12 weeks of treatment with upadacitinib (15 mg and 30 mg, once-daily) in SELECT-NEXT and SELECT-BEYOND and after 14 weeks of treatment in SELECT-MONOTHERAPY.^1,2,3 Additionally, improvements were reported in fatigue and work instability in SELECT-NEXT and patients' physical component of health-related quality of life in SELECT-NEXT and SELECT-BEYOND at 12 weeks.^1,2 Upadacitinib is not approved by regulatory authorities and its safety and efficacy have not been established.

AbbVie has previously announced positive top-line results from SELECT-NEXT, SELECT-BEYOND and SELECT-MONOTHERAPY.^12,13,14

"Across three Phase 3 studies with different patient populations, patients treated with upadacitinib reported improvements in physical function, joint pain and morning stiffness," said Marek Honczarenko, M.D., Ph.D., vice president, immunology development, AbbVie. "These results show upadacitinib's potential to address the challenges rheumatoid arthritis patients face when performing everyday activities."

Patient-reported outcomes are an important component of understanding how rheumatoid arthritis patients perceive the physical, psychological and social impact of their disease.¹⁵ Using patient-reported outcomes to assess disease activity allows patients to take an active role in their treatment journey through shared decision making with their rheumatologists and healthcare team.

"The deterioration and impairment in physical function associated with rheumatoid arthritis can dramatically impact patients' quality of life. Patients included in SELECT-NEXT and SELECT-BEYOND had difficult-to-treat disease resistant to prior therapies," said Dr. Vibeke Strand, adjunct clinical professor in the Division of Immunology/Rheumatology at Stanford University School of Medicine. "It is particularly noteworthy to see that improvements in clinical efficacy previously reported from these studies were also reflected in patient-reported outcome measures, such as physical function, morning stiffness and pain."

Physical Function^1,2

• In SELECT-NEXT, improvements in physical function, as measured by the Health Assessment Questionnaire-Disability Index (HAQ-DI)*, were observed as early as one week after initial treatment with upadacitinib across both doses. At week 12, 72/68 percent of patients receiving 15/30 mg of upadacitinib had improvements in physical function (HAQ-DI) compared with 49 percent of patients receiving placebo (p<0.05).
• In SELECT-BEYOND, improvements in physical function (HAQ-DI) were observed as early as two weeks after initial treatment with upadacitinib across both doses. At week 12, 63/55 percent of patients receiving 15/30 mg of upadacitinib had improvements in physical function (HAQ-DI) compared with 37 percent of patients receiving placebo (p<0.05).

Joint Pain^1,2

• In SELECT-NEXT, patients reported reductions in pain, as measured by the Patient's Assessment of Pain by Visual Analog Scale (VAS)**, as early as one week after initial treatment with both doses of upadacitinib. At week 12, 73 percent of patients receiving either dose of upadacitinib reported a reduction in pain compared with 44 percent of patients receiving placebo (p<0.05).
• In SELECT-BEYOND, patients also reported reductions in pain as early as two weeks after initial treatment with both doses of upadacitinib. At week 12, 74/64 percent of patients receiving 15/30 mg of upadacitinib reported a reduction in pain compared with 46 percent of patients receiving placebo (p<0.05).

Morning Stiffness***^1,2

• In SELECT-NEXT, patients receiving upadacitinib reported reductions in the severity of morning stiffness as early as one week after initial treatment with both doses of upadacitinib. At week 12, 76/80 percent of patients receiving 15/30 mg of upadacitinib reported reductions in the severity of morning joint stiffness compared to 60 percent of patients receiving placebo (p<0.05). Additionally, patients treated with both doses of upadacitinib had a mean reduction of 85 minutes in the duration of morning stiffness compared to 34 minutes with placebo (p<0.05) at week 12.
• In SELECT-BEYOND, patients receiving upadacitinib reported reductions in the severity of morning stiffness as early as one week after initial treatment with both doses of upadacitinib. At week 12, 80/72 percent of patients receiving 15/30 mg of upadacitinib reported reductions in the severity of morning joint stiffness compared to 56 percent for placebo (p<0.05). Additionally, patients reported a mean reduction of 81/80 minutes in duration of morning stiffness among those receiving 15/30 mg of upadacitinib compared to 15 minutes for placebo (p<0.05) at week 12.

In a third Phase 3 trial, SELECT-MONOTHERAPY, upadacitinib monotherapy demonstrated improvements in patients' physical function (HAQ-DI) and health-related quality of life (Short Form 36 Health Survey) as well as reductions in the duration of morning joint stiffness compared to patients receiving methotrexate.³ Additionally, upadacitinib treated patients reported clinically meaningful improvements as early as week two for physical function, pain and morning stiffness compared to week eight (physical function) and week four (pain and morning stiffness) for those treated with methotrexate. Additional patient-reported outcomes data from SELECT-MONOTHERAPY will be presented at a future medical meeting and published in a peer-reviewed publication.³

Safety results from all three SELECT trials have been previously reported.^12-14

About SELECT-NEXT¹

SELECT-NEXT is a Phase 3, multicenter, randomized, double-blind, placebo-controlled study designed to evaluate the safety and efficacy of two doses (15 mg and 30 mg) of upadacitinib in adult patients with moderate to severe rheumatoid arthritis who are on a stable dose of csDMARDs and have had an inadequate response to csDMARDs. The primary endpoints included the percentage of subjects achieving an ACR20 response and low disease activity (LDA) after 12 weeks of treatment. Key secondary endpoints included proportion of patients achieving ACR50 and ACR70 response and clinical remission at week 12. Patient-reported outcome responses were evaluated in patients who continued in the five-year extension phase of SELECT-NEXT comparing upadacitinib (15 mg and 30 mg) and placebo. Patient-reported outcomes measured included physical function (Health Assessment Questionnaire Disability Index [HAQ-DI]), Patient's Global Assessment of Disease Activity (PtGA) by visual analog scale (VAS), pain by VAS, fatigue by Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), duration and severity of morning (AM) stiffness, health-related quality of life (QoL) by Short Form 36 Health Survey (SF-36), and Work Instability Scale for RA (RA-WIS). More information on this trial can be found at www.clinicaltrials.gov (NCT02675426).

About SELECT-BEYOND²

SELECT-BEYOND is a Phase 3, multicenter, randomized, double-blind, placebo-controlled study designed to evaluate the safety and efficacy of two once-daily doses (15 mg and 30 mg) of upadacitinib in adult patients with moderate to severe rheumatoid arthritis who are on a stable dose of conventional synthetic DMARDs (csDMARDs) and have had an inadequate response or intolerance to bDMARDs. The primary endpoints included the percentage of subjects achieving an ACR20 response and low disease activity (LDA) after 12 weeks of treatment. Secondary endpoints included proportion of patients achieving ACR50 and ACR70 response at week 12. In this post-hoc analysis, data from SELECT-BEYOND was used to compare patient-reported outcome responses between upadacitinib (15 mg and 30 mg) and placebo. Patient-reported outcomes included physical function by Health Assessment Questionnaire Disability Index (HAQ-DI), Patient's Global Assessment of Disease Activity (PtGA) by visual analog scale (VAS), pain by VAS, duration and severity of morning (AM) stiffness, health-related quality of life (QoL) by Short Form 36 Health Survey (SF-36), and severity of insomnia by Insomnia Severity Index (ISI). More information on this trial can be found at www.clinicaltrials.gov (NCT02706847).

About SELECT-MONOTHERAPY³

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, Health Assessment Questionnaire Disability Index (HAQ-DI), duration of morning (AM) stiffness and health-related quality of life (QoL) by Short Form 36 Health Survey (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 an investigational oral agent engineered to selectively inhibit JAK1, which plays an important role in the pathophysiology of immune-mediated disorders.^4,5 Phase 3 trials of upadacitinib in rheumatoid arthritis, psoriatic arthritis and Crohn's disease are ongoing and it is also being investigated to treat ulcerative colitis, ankylosing spondylitis and atopic dermatitis.^6-11

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 or LinkedIn.

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.

Key Terms
*HAQ-DI: Health Assessment Questionnaire Disability Index (HAQ-DI) is a patient questionnaire with questions regarding the patient's illness and how it affects their daily life activities.
**Pain: Patient's assessment of pain using the visual analog scale (VAS) determines pain intensity.
***Severity and Duration of Morning stiffness: Morning stiffness severity and duration is determined by the Patient's Assessment of Severity and Duration of Morning Stiffness questionnaire.

References

1. Strand, V et al. Upadacitinib Improves Patient-Reported Outcomes In Patients With Rheumatoid Arthritis And Inadequate Response To Conventional Synthetic Disease-Modifying Anti-Rheumatic Drugs: Results From SELECT-NEXT. Annual European Congress of Rheumatology (EULAR 2018). June 2018.
2. Strand, V et al. Upadacitinib In Patients With Active Rheumatoid Arthritis And Inadequate Response Or Intolerance To Biological DMARDs: A Phase 3 Randomized, Placebo-Controlled, Doubleblind Study Of A Selective JAK1 Inhibitor. Annual European Congress of Rheumatology (EULAR 2018). June 2018.
3. Smolen, J et al. Upadacitinib As Monotherapy: A Phase 3 Randomized Controlled Double-Blind Study In Patients With Active Rheumatoid Arthritis And Inadequate Response To Methotrexate. Annual European Congress of Rheumatology (EULAR 2018). June 2018.
4. 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.
5. Pipeline – Our Science | AbbVie. AbbVie. 2017. Available at: https://www.abbvie.com/our-science/pipeline.html. Accessed on March 29, 2018.
6. A Study Comparing ABT494 to Placebo in Subjects With Rheumatoid Arthritis on a Stable Dose of Conventional Synthetic Disease Modifying Antirheumatic Drugs (csDMARDs) Who Have an Inadequate Response to csDMARDs Alone (SELECT-NEXT). ClinicalTrials.gov. 2018. Available at: https://clinicaltrials.gov/ct2/show/NCT02675426. Accessed on March 29, 2018.
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. 2018. Available at: https://clinicaltrials.gov/ct2/show/NCT03104400. Accessed on March 29, 2018.
8. 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 March 29, 2018.
9. 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 March 29, 2018.
10. 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 March 29, 2018.
11. Phase 2b AD Dose Ranging Study (40wk) N=160. ClinicalTrials.gov. 2018. Available at: https://clinicaltrials.gov/ct2/show/NCT02925117. Accessed on March 29, 2018.
12. AbbVie. Data on File, ABVRRTI64466.
13. AbbVie. Data on File, ABVRRTI64730.
14. AbbVie. Data on File, ABVRRTI65458.
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. Accessed on March 8, 2018.

SOURCE AbbVie