Janus Kinase Inhibitors Improve Disease Activity and Patient-Reported Outcomes in Rheumatoid Arthritis: A Systematic Review and Meta-Analysis of 24,135 Patients

Tóth, L; Juhász, Márk; Szabó, L.; Abada, Alan; Kiss, Fruzsina; Hegyi, Péter; Farkas, Nelli; Nagy, György; Helyes, Zsuzsanna

doi:10.3390/ijms23031246

Cited by 28 publications

(16 citation statements)

References 116 publications

(188 reference statements)

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“…In the MTX-IR population in which baricitinib and adalimumab were compared, the reduction in pain and disease activity observed with baricitinib was significantly greater than with adalimumab. These findings are consistent with a meta-analysis assessing a range of outcomes for JAK inhibitors versus placebo, MTX, or bDMARDs in RA, which demonstrated significant improvements in pain VAS and in measures of disease activity including CDAI, for JAK inhibitors versus placebo and in pain VAS and some measures of disease activity versus TNFi 17 . At some time points in the present study, greater improvement in fatigue was observed with baricitinib than with adalimumab; however, those differences were relatively limited.…”

Section: Discussionsupporting

confidence: 87%

Relative Impact of Pain and Disease Activity on Improvements in Fatigue

Fautrel

Wang

et al. 2022

J Clin Rheumatol

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Background/Objective Fatigue is common in patients with rheumatoid arthritis (RA). We assessed the relative impact of pain and disease activity on improvements in fatigue in 2 phase 3 baricitinib clinical trials. Methods RA-BEAM (NCT01710358) and RA-BEACON (NCT01721044) were randomized, double-blind, placebo-controlled studies in adults with moderate to severe RA. RA-BEAM assessed baricitinib + methotrexate (MTX) and adalimumab + MTX in patients with prior inadequate response/intolerance (IR) to MTX (MTX-IR). RA-BEACON assessed patients with IR to ≥1 biologic disease-modifying antirheumatic drug (bDMARD-IR). Measures included the Functional Assessment of Chronic Illness Therapy—Fatigue scale, Clinical Disease Activity Index (CDAI) for RA, and pain visual analog scale (VAS). Analyses were implemented separately for each study. Results Significant improvements were seen in disease activity and pain, which were greater with baricitinib versus adalimumab. A statistically significant improvement was seen in fatigue with both active treatments versus placebo. Moderate correlations were observed between improvements in disease activity and fatigue and between improvements in pain and fatigue in both MTX-IR and bDMARD-IR patients. Reductions in pain (≥50%) and remission or low disease activity (CDAI ≤10) had significant associations with fatigue improvement at week 24. In mediation analysis, improvements in fatigue attributable to CDAI and pain VAS in MTX-IR patients were 31% and 52%, respectively, for baricitinib, and 30% and 47%, respectively, for adalimumab. In bDMARD-IR patients, improvement in fatigue was attributed 48% to CDAI and 48% to pain VAS. Conclusions In both MTX-IR and bDMARD-IR patients, a large proportion of improvements in fatigue across treatment arms were accounted for by improvements in pain and disease activity.

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Section: Discussionsupporting

confidence: 87%

Relative Impact of Pain and Disease Activity on Improvements in Fatigue

Fautrel

Wang

et al. 2022

J Clin Rheumatol

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“…In our study, JAKi were associated with HAQ-DI normalization and pain VAS reduction compared with TNFi at 6 months after starting treatment. The effectiveness of JAKi on patient-oriented outcomes among RA patients are well-established [25], including the effectiveness on pain among RA patients with low levels of in ammation [26]. This might be due to the direct effect of JAKi on signals on pain sensitivity [27], or the rapid-acting nature of these agents, within 24 hours [24], one week [28], and two weeks [10], which may also contribute to the improvements in HAQ-DI in the early stages of treatment.…”

Section: Discussionmentioning

confidence: 99%

Predictors of functional improvement and pain reduction in rheumatoid arthritis patients who achieved low disease activity with disease-modifying antirheumatic drugs: a retrospective study of the FIRST Registry

Ochi,

Sonomoto,

Nakayamada

et al. 2024

Preprint

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Background Rheumatoid arthritis (RA) patients sometimes different levels of improvement in health assessment questionnaire-disability index (HAQ-DI) and subjective pain visual analogue score (VAS) even after achieving low disease activities (LDA). This study aimed to identify factors associated with improvement in HAQ-DI and pain VAS among those who achieved LDA. Methods Data of the FIRST registry, a multi-institutional cohort of RA patients treated with biological and targeted-synthetic DMARDs (b/tsDMARDs) were analyzed. Patients who were enrolled from August 2013 to February 2023 and who achieved clinical LDA [clinical disease activity index (CDAI) ≤ 10.0] at 6 months after starting treatment were included. Multiple logistic regression analyses were conducted to identify the factors that associated with achieving HAQ-DI normalization (< 0.5), HAQ-DI improvement (by > 0.22), or pain VAS reduction (≤ 40mm). Results Among 1424 patients who achieved LDA at 6 months, 732 patients achieved HAQ-DI < 0.5 and 454 achieved pain VAS reduction. The seropositivity and the use of JAK inhibitor compared with TNF inhibitor were associated with both HAQ-DI < 0.5 and pain VAS reduction at 6 months. On the other hand, older age, past failure in ≥ 2 classes of b/tsDMARDs, higher HAQ-DI at baseline, and use of glucocorticoid were associated with the lower likelihood of HAQ-DI normalization and pain VAS reduction. Longer disease duration, being female, and higher disease activity at baseline was negatively associated HAQ-DI normalization alone. Comorbidities were not associated with the outcomes. Conclusions These results suggest some preferable treatment may exist for improvement of HAQ-DI and pain VAS reduction in the early stage of the treatment, which is a clue to prevention of a criteria of difficult-to-treat RA.

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“…A recent extensive meta-analysis, demonstrating that JAKi showed a significantly greater pain-relieving effect compared with biologic DMARDs (bDMARDs) supported these findings [28 ▪ ] In addition, the CRP values indicating the intensity of the inflammatory reaction were also lower in the JAK inhibitor group [28 ▪ ]. In addition, a post-hoc analysis of phase 3 trials of baricitinib found pain reduction was similar between opioid users and nonusers, which was not observed for adalimumab, suggesting opioids attenuate pain reduction effects [29].…”

Section: Dmard and Biological Considerationsmentioning

confidence: 95%

Fibromyalgia and centralized pain in the rheumatoid arthritis patient

Minhas

Murphy

Clauw

2023

Current Opinion in Rheumatology

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Purpose of reviewIndividuals with rheumatoid arthritis (RA) have traditionally been characterized as having nociceptive pain, leading to the assumption that effective immunosuppression should be enough to provide effective pain management. However, despite therapeutic advancements providing excellent control of inflammation, patients continue to have significant pain and fatigue. The presence of concurrent fibromyalgia, driven by augmented central nervous system processing and largely unresponsive to peripheral therapies, may contribute to this pain persistence. This review provides updates on fibromyalgia and RA as relevant for the clinician. Recent findingsPatients with RA have high levels of concomitant fibromyalgia and nociplastic pain. The presence of fibromyalgia can lead to higher scores on disease measures, erroneously indicating that worse disease is presently leading to the increased use of immunosuppressives and opioids. Disease scores that provide a comparison between patient-reported and provider-reported and clinical factors may be helpful to indicate centralized pain. IL-6 and Janus kinase inhibitors, in addition to targeting peripheral inflammation, may provide pain relief by acting on peripheral and central pain pathways. SummaryCentral pain mechanisms that may be contributing to pain in RA are common and should be distinguished from pain directly arising from peripheral inflammation.

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Janus Kinase Inhibitors Improve Disease Activity and Patient-Reported Outcomes in Rheumatoid Arthritis: A Systematic Review and Meta-Analysis of 24,135 Patients

Cited by 28 publications

References 116 publications

Relative Impact of Pain and Disease Activity on Improvements in Fatigue

Relative Impact of Pain and Disease Activity on Improvements in Fatigue

Predictors of functional improvement and pain reduction in rheumatoid arthritis patients who achieved low disease activity with disease-modifying antirheumatic drugs: a retrospective study of the FIRST Registry

Fibromyalgia and centralized pain in the rheumatoid arthritis patient

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