Achieving Pain Control in Rheumatoid Arthritis with Baricitinib or Adalimumab Plus Methotrexate: Results from the RA-BEAM Trial

Abstract

The purpose of the study was to assess the proportion of patients who achieve pain relief thresholds, the time needed to reach the thresholds, and the relationship between pain and inflammation among patients with rheumatoid arthritis (RA) and an inadequate response to methotrexate in RA-BEAM (NCT0170358). A randomized, double-blind trial was conducted, comparing baricitinib (N = 487), adalimumab (N = 330), and placebo (N = 488) plus methotrexate. Pain was evaluated by patient’s assessment on a 0–100 mm visual analog scale (VAS). The following were assessed through a 24-week placebo-controlled period: the proportion of patients who achieved ≥30%, ≥50%, and ≥70% pain relief, the time to achieve these pain relief thresholds, remaining pain (VAS ≤ 10 mm, ≤20 mm, or ≤40 mm), and the relationship between inflammation markers and pain relief. Baricitinib-treated patients were more likely (p < 0.05) to achieve ≥30%, ≥50%, and ≥70% pain relief than placebo- and adalimumab-treated patients, as early as Week 1 vs. placebo and at Week 4 vs. adalimumab. A greater proportion of baricitinib-treated patients achieved ≤20 mm or ≤40 mm remaining pain vs. placebo- and adalimumab-treated patients. Baricitinib-treated patients tended to demonstrate consistent pain relief independent of levels of inflammation control. In RA patients with an inadequate response to methotrexate, baricitinib provided greater and more rapid pain relief than adalimumab and placebo. Analyses suggest the relationship between inflammation and pain may be different for baricitinib and adalimumab treatments.

Pain in Rheumatoid Arthritis: Could JAK Inhibition be the Answer?

“…A recent post-hoc analysis of the RA-BEAM trial focussed specifically on pain outcomes. 47 In RA-BEAM, a Phase 3 clinical trial of baricitinib, an oral, selective inhibitor of JAK1 and JAK2, baricitinib plus methotrexate (MTX) was associated with significant clinical improvements compared to patients treated with adalimumab plus MTX or placebo plus MTX. Baricitinib- and adalimumab-treated patients demonstrated similar improvement in SJC, with both groups demonstrating statistically significantly greater improvement relative to the placebo group beginning at Week 1 that was maintained through the placebo-controlled period (Week 24).…”

“…Furthermore, this differential effect became more marked as the pain relief thresholds increased, with approximately 40% of the patients receiving baricitinib achieving ≥70% pain relief from baseline by Week 24. 47 …”

Patient-Centered Care in Psoriatic Arthritis—A Perspective on Inflammation, Disease Activity, and Psychosocial Factors

“…JAK inhibitors may alleviate pain more rapidly and among a greater proportion of patients. Novel drug targets within JAK-STAT-signaling pathways may affect pronociceptive and inflammatory mechanisms to a greater extent than current agents [ 92 , 93 ]. On the other hand, if pain results from both cognitive, behavioral, and inflammatory components, a conjunction of different pharmacologic and psychotherapeutic treatment modalities can be useful.…”

Baricitinib: New Pharmacotherapy Options for Rheumatoid Arthritis and Other Immune-Mediated Inflammatory Rheumatic Diseases

“…В связи с этим представляют интерес данные субанализа РКИ RA-BEAM, в котором было показано, что лечение БАРИ ассоциировалось с более выраженным и быстрым уменьшением интенсивности боли в суставах, чем на фоне АДА и ПЛ, на 1-4-й и 24-й неделях (p<0,05) [91], независимо от динамики активности воспаления. Кроме того, через 24 нед у пациентов в состоянии ремиссии / низкой активности, получавших лечение БАРИ, показатели выраженности боли и физической функции (HAQ-DI) были лучше, чем в группе ПЛ (p<0,001 и p<0,01 соответственно) и АДА (p<0,05 в обоих случаях) [92].…”

“…Механизмы антиноцицептивного эффекта БАРИ (как и других ингибиторов JAK) не ясны. Обсуждается значение гранулоцитарномакрофагального колониестимулирующего фактора (ГМ-КСФ) [91], сигнализация которого регулируется JAK2, участвующего в развитии боли при экспериментальном остеоартрите [96,97]. Нельзя исключить участие механизмов, зависящих от интерлейкина 6 (ИЛ6), который также играет важную роль в развитии боли на уровне центральной нервной системы [98,99].…”