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Upadacitinib monotherapy appears promising in RA patients with inadequate methotrexate response

Key clinical point: The trial findings are supportive of monotherapy with the JAK inhibitor upadacitinib as a potential treatment option for RA patients with inadequate response to methotrexate.

Major finding: Overall, 40%-50% of patients with inadequate response to methotrexate achieved low disease activity with upadacitinib monotherapy, and almost 20% achieved stringent remission by week 14.

Study details: SELECT-MONOTHERAPY is a phase 3, randomized, placebo-controlled, double-blind trial involving 648 patients with active RA despite treatment with methotrexate.

Disclosures: The study was funded by AbbVie. Most authors reported financial ties to AbbVie and other companies marketing rheumatoid arthritis treatments. Five authors are employees of AbbVie.

Citation:

Smolen JS et al. Lancet. 2019;393[10188]:2303-11. doi: 10.1016/S0140-6736(19)30419-2.

Commentary:

Treatment recommendations for the management of RA do not currently include the use of novel disease-modifying antirheumatic drugs (DMARDs) as monotherapy. However, there is growing interest in this concept, most likely because of poor tolerability and contraindications to conventional synthetic DMARDs such as methotrexate.

The SELECT-NEXT trial published last year by Professor Gerd Burmester from the Charité-Universitätsmedizin, Berlin, evaluated upadacitinib in patients with active RA while on methotrexate.

The observed treatment effects of SELECT-NEXT and the current trial by Prof. Smolen and associates are similar for both control groups (responders: 36% vs. 41% on methotrexate plus placebo) and for the upadacitinib treatment groups, regardless of concomitant methotrexate status (64% on methotrexate plus upadacitinib 15 mg or 66% on methotrexate plus upadacitinib 30 mg vs. 68% on upadacitinib 15 mg or 71% on upadacitinib 30 mg).

Prof. Smolen and associates chose a trial design that assessed the continuation of methotrexate plus placebo versus switching from methotrexate to upadacitinib monotherapy, but does this research question adequately reflect the question often raised in clinical practice: Should a novel DMARD be added to methotrexate or should patients switch from methotrexate to a novel DMARD?

The rheumatology community is largely in agreement that the use of novel DMARDs in RA monotherapy might present a new opportunity, particularly for RA patients with active disease while on methotrexate.

But we now need a trial that compares a switch versus an add-on strategy to adequately answer the question on the treatment of resistant RA.

These comments are adapted from an accompanying editorial by Anna Moltó, MD, and Maxime Dougados, MD, both with the rheumatology department at Cochin Hospital, Paris (Lancet. 2019;393[10188]:2277-8. doi: 10.1016/S0140-6736(19)30768-8). The rheumatology department at Cochin Hospital has received grants to do clinical studies and trials from AbbVie and other manufacturers of drugs for RA. Both Dr. Dougados and Dr. Moltó reported receiving personal fees for advisory boards and symposia from AbbVie and other manufacturers of drugs for RA outside the area of work commented on here.