Filgotinib in Rheumatoid Arthritis: A Profile of Its Use

Abstract

Filgotinib (Jyseleca®), an oral Janus kinase (JAK) inhibitor, is approved as monotherapy or in combination with methotrexate to treat moderate to severe active rheumatoid arthritis (RA) in adults who have an inadequate response or intolerance to one or more disease-modifying antirheumatic drugs (DMARDs). In phase 3 trials, once-daily filgotinib was generally well tolerated and associated with an improvement in RA signs and symptoms as well as physical function in patients with an inadequate response to ongoing methotrexate, an inadequate response to ongoing conventional synthetic DMARDs plus an inadequate response or intolerance to prior biologic DMARDs, or limited or no prior exposure to methotrexate. In addition, filgotinib was noninferior to adalimumab in terms of low disease activity response rate (DAS28-CRP ≤ 3.2) in patients with an inadequate response to methotrexate. Filgotinib also appeared to inhibit the radiographic progression of joint damage and led to low disease activity or disease remission (DAS28-CRP < 2.6). Filgotinib showed sustained efficacy, and the safety profile of filgotinib longer term was similar to that in the phase 2 and 3 trials. Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease mainly affecting the small joints of the hands and feet. While there is no cure for RA, biologic disease-modifying antirheumatic drugs (DMARDs), which target the inflammatory cytokines (and their receptors) involved in RA, can achieve low disease activity or disease remission. However, these drugs are not always effective or well tolerated and their administration routes (intravenous or subcutaneous) can be a barrier to use. More recently, oral drugs that act on pathways downstream of cytokine receptors have been developed. These drugs, the Janus kinase (JAK) inhibitors, are targeted synthetic DMARDs. Filgotinib (Jyseleca®), a second-generation JAK inhibitor, improves joint swelling, disease activity, pain, and physical functioning and reduces progression of joint damage in adults with moderate to severe active RA and is generally well tolerated. Like other JAK inhibitors, filgotinib is recommended in treatment guidelines as an effective alternative to biologic DMARDs in adults with moderate to severe active RA who have not responded adequately to or who do not tolerate other DMARDs.