More good news for AbbVie in rheumatoid arthritis

AbbVie has reported positive top-line results for its oral JAK1-selective inhibitor in rheumatoid arthritis (RA), bringing it closer to a potential new early treatment option for patients.

The company’s SELECT-EARLY trial showed that both doses of upadacitinib monotherapy (15 mg and 30 mg) met the primary endpoints of ACR50 at week 12 and clinical remission at week 24 versus methotrexate (MTX). All ranked secondary endpoints were also met.

The news boosts AbbVie’s efforts to find new revenue streams as its inflammatory diseases blockbuster Humira approaches the end of its patent, and follows previous positive results for upadacitinib announced in June 2017.

Upadacitinib, an oral JAK1-selective inhibitor, is being investigated as a monotherapy treatment compared to methotrexate monotherapy in adult patients with moderate-to-severe RA who were methotrexate-naïve. JAK1 plays an important role in the pathophysiology of immune-mediated disorders.

Methotrexate is commonly used as a first-line therapy in RA, but many patients do not respond to, or cannot tolerate, it.

"SELECT-EARLY is the fifth pivotal trial that will support regulatory submissions for upadacitinib in rheumatoid arthritis later this year," said AbbVie’s chief scientific officer Michael Severino, MD. "Results from SELECT-EARLY further support our belief that upadacitinib has the potential to be an important new treatment option for patients with rheumatoid arthritis."

RA affects an estimated 23.7 million people worldwide and early intervention with an effective treatment is critical to control the disease and prevent permanent joint damage and impaired physical function.

"It is very encouraging that approximately half of patients achieved the desired clinical target of remission in six months with upadacitinib monotherapy at either dose. Outcomes from this trial address the need for additional monotherapy options early in the disease," said Ronald van Vollenhoven, MD, PhD, director of the Amsterdam Rheumatology and Immunology Centre ARC and professor of rheumatology, University of Amsterdam and Free University. "Results suggest upadacitinib as a monotherapy has the potential to control rheumatoid arthritis and reduce the risk of permanent bone and joint damage for methotrexate-naïve patients."

A significantly higher proportion of upadacitinib patients in both doses achieved superior responses compared to patients on methotrexate at week 12 and 24. Results at week 12 showed that, of patients receiving an oral once-daily dose of upadacitinib 15/30 mg, 52/56% achieved ACR50, respectively, compared with 28% of patients receiving methotrexate. At week 24, clinical remission was achieved by 48/50% of patients receiving upadacitinib 15/30 mg, respectively, compared to 18% of patients receiving methotrexate.

At week 12, 76/77% of patients receiving 15/30 mg of upadacitinib, achieved ACR20, respectively, compared to 54% in the methotrexate group. Additionally, ACR70 was achieved by 32/37% of patients receiving 15/30 mg of upadacitinib, respectively, compared to 14% receiving methotrexate at week 12. Clinical remission was achieved by 36% and 41% of patients in the 15 mg and 30 mg groups, respectively, compared to 14% of patients receiving methotrexate at week 12. Low disease activity was achieved by 53% and 55% of patients in the 15 mg and 30 mg groups, respectively, compared to 28% of patients receiving methotrexate at week 12.

At week 24, 79/60/44% patients receiving the 15 mg dose of upadacitinib and 78/66/50% of patients receiving the 30 mg dose of upadacitinib achieved ACR20/50/70 response, compared to 59/33/18% of patients receiving methotrexate. Low disease activity was achieved by 60% and 65% of patients in the 15 mg and 30 mg groups, respectively, compared to 32% of patients receiving methotrexate at week 24.

Following 24 weeks of treatment, both doses of upadacitinib monotherapy significantly inhibited radiographic progression compared to methotrexate. The inhibition of joint damage is important for RA patients as this can lead to permanent loss of function and subsequent disability.

SELECT-EARLY is a phase 3, multicentre, randomised, double-blind, parallel-group, active comparator-controlled study.

The SELECT programme is evaluating more than 4,000 patients with moderate-to-severe RA in six studies.

Upadacitinib is also being studied in psoriatic arthritis, Crohn's disease, ulcerative colitis, ankylosing spondylitis and atopic dermatitis.