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13-12-2021 | Mental health | Adis Journal Club | Article

Rheumatology and Therapy

Association Between Janus Kinase Inhibitors Therapy and Mental Health Outcome in Rheumatoid Arthritis: A Systematic Review and Meta-analysis

Authors: Ghazala M. H. Shamail, Madhumitha Haridoss, Meenakumari Natarajan, Vasna Joshua & Bhavani Shankara Bagepally



Rheumatoid arthritis (RA) is a chronic debilitating illness, usually associated with mental health ailments. Literature reports contradictory observations about the association between recent RA pharmacotherapies and mental health. We systematically reviewed RA randomized control trials to synthesize the association between Janus kinases (JAK) inhibitors therapy and mental health.


We systematically searched clinical trials of JAK inhibitor intervention reporting mental health outcomes using short form-36 (SF-36) in PubMed, Embase, and Scopus databases from inception to February 2021. We have selected the studies and extracted the data, adhering to Preferred Reporting Items of Systematic reviews and Meta-Analysis (PRISMA) guidelines. We have pooled the mean change of SF-36 mental component score (MCS) between JAK inhibitors and comparator therapy with a 95% confidence interval.


Of the 2915 searched studies for systematic review, 19 studies involving 14,323 individuals were included for the meta-analysis. The pooled mean reduction in SF-36 MCS scores (after minus before) with JAK inhibitors was 4.95 (4.41–5.48). The pooled mean difference of incremental mean change in SF-36 MCS score between JAK monotherapy and comparator was 1.53 (0.88–2.18). The improvement in SF-36 MCS scores with JAK inhibitor therapy is greater than the minimum clinically important difference (MCID) value of 2.5. However, on separate analysis with comparator drugs like methotrexate and standard treatment, the MCS scores did not exceeded the MCID value and were also not statistically significant.


JAK inhibitors results in clinically meaningful improvement in the mental health scores of the RA patients.

PROSPERO Registration ID

2021 CRD42021234466.

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Key Summary Points

What is already known about this subject?

From individual trials, each JAK inhibitor, separately had an impact on the mental health in patients with rheumatoid arthritis, but the synthesized result was limited.

What are the new findings?

From our study, the pooled results of JAK monotherapy was found to have a clinically meaningful improvement in mental health compared to baseline/pre-treatment mental health. 

The pooled results of JAK inhibitors + methotrexate was found to be effective than disease-modifying antirheumatic drugs in improving the mental health of RA patients.

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