Outcomes after rheumatoid arthritis patients complete their participation in a long-term observational study with tofacitinib combined with methotrexate: practical and ethical implications in vulnerable populations after tofacitinib discontinuation

Abstract

To describe disease activity and disability during the first year of follow-up, from rheumatoid arthritis (RA) patients who discontinue tofacitinib after they end participation in a clinical trial. From 2008 to 2016, 36 patients were enrolled in the "Long term follow-up study with tofacitinib (and methotrexate) for RA treatment". At the end of the study, tofacitinib was discontinued and patients were proposed to enter an observational study; 35 agree and had scheduled evaluations at baseline, at 15 and 30 days of follow-up, at month 2 and 3, and thereafter every 3 months. Disease activity was evaluated as per DAS28-ESR and disability as per HAQ. During follow-up, treatment was treat-to-target oriented, only conventional DMARDs were indicated. Descriptive statistics and nonparametric test were used. The study was approved by IRB. Patients were primarily females (N = 34), had median (Q25-75) age of 52 years (45-58), and had received tofacitinib for a median of 7.9 years (6.3-8.3). The proportion of patients with remission and low disease activity decreased from day 30 of follow-up and recovered after 270 days, meanwhile patients with high disease activity increased from 0% at baseline to 6.3% at 1 year. At study entry, 20 patients had remission/low disease activity; during follow-up, 85% deteriorated after (median) 30 days; among them, 23.5% recovered their baseline status after a median of 172.5 days. The HAQ showed a similar behavior, but 66.7% recovered. A substantial proportion of RA patients deteriorated outcomes early after tofacitinib cessation; some patients recovered baseline status with traditional DMARDS.

Outcomes of dose reduction, withdrawal, and restart of tofacitinib in patients with rheumatoid arthritis: a prospective observational study

“…Recently, two studies examined the outcomes of tofacitinib discontinuation during 1 year of post-treatment follow-up among RA patients who had achieved remission or low CDAI in clinical trials and long-term extension studies [21,22]. Among these studies, one conducted in a Japanese cohort showed that 37% (20 out of 54 patients) in the discontinuation group continued without flare while tofacitinib-free [21].…”

“…Among these studies, one conducted in a Japanese cohort showed that 37% (20 out of 54 patients) in the discontinuation group continued without flare while tofacitinib-free [21]. In another study in Mexican patients, disease activity worsened following discontinuation of tofacitinib in 85% (17 out of 20 patients) [22]. In the present study in Japanese patients, the probability of flare-free survival at 12 months as estimated by the Kaplan-Meier approach was 32% in the discontinuation group, 66% in the dose-reduction group, and 94% in the continuation group.…”

“…The only data available were obtained from RA patients who had stopped tofacitinib after completing clinical trials and long-term extension studies. These patients had been on tofacitinib treatment for long periods of time before immediate discontinuation, and none of them received a dose-reduction strategy [21,22].…”

Efficacy and safety of tofacitinib for immune-mediated inflammatory rheumatic diseases (Part I)

“…Особый интерес представляют исследования, касающиеся оптимизации терапии РА после достижения ремиссии, а именно -снижения дозы препаратов или отмены терапии [124,125]. В одном наблюдательном исследо-вании было показано, что у 37% (20 из 54) пациентов после отмены ТОФА не наблюдалось обострения заболевания [126], а по данным другого исследования, обострение заболевания после отмены ТОФА имело место у 85% (17 из 20) пациентов [127]. Представляют интерес материалы проспективного исследования, в которое вошли 100 пациентов с высокой/умеренной активностью РА, получавшие лечение ТОФА (5 мг 2 раза в день) [128].…”

Tofacitinib in rheumatoid arthritis: what is new?

“…Особый интерес представляют исследования, касающиеся оптимизации терапии РА после достижения ремиссии, а именно изучение возможности снижения дозы препаратов или отмены терапии [74]. В двух исследованиях отмена ТОФА приводила к развитию обострения у 63% [75] и 85% пациентов [76]. В проспективном исследовании [77] вероятность сохранения ремиссии после прекращения лечения ТОФА составила 32%, а повторное назначение препарата позволило быстро достичь ремиссии у 93% пациентов, у которых ТОФА был отменен, и у 100% пациентов, у которых развитие обострения имело место при снижении дозы ТОФА.…”