Comparative Safety of JAK Inhibitors vs TNF Antagonists in Immune-Mediated Inflammatory Diseases: A Systematic Review and Meta-Analysis

Solitano, V; Ahuja, D; Lee, HH; Gaikwad, R; Yeh, KH; Facciorusso, A; Singh, AG; Ma, C; Ananthakrishnan, AN; Yuan, Y; Singh, N; Jairath, V; Singh, S

doi:10.1001/jamanetworkopen.2025.31204

Across rheumatic diseases

Comparative Safety of Janus Kinase (JAK) Inhibitors vs Tumor Necrosis Factor (TNF) Antagonists in Immune-Mediated Inflammatory Diseases: A Systematic Review and Meta-Analysis

JAMA Netw OpenPublished 2 Sep 2025Systematic review and meta-analysis of observational studies

Pooled result · Serious infectionsResultPooled hazard ratio 1.05 95% CI 0.97–1.13

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Authors' conclusion

The head-to-head studies in this systematic review and meta-analysis did not identify any meaningful difference in the risk of serious infections, malignant neoplasms, or MACEs with JAK inhibitor vs TNF antagonist use across all IMIDs, with low overall incidence. JAK inhibitor use was associated with a slightly higher risk of VTE.

Study context

Population: Adults (≥18 years) with immune-mediated inflammatory diseases (IMIDs) (including RA, inflammatory bowel disease, psoriasis or PsA, or spondyloarthropathy)
Participants: 813,881 adults42 studies

Comparison: JAK inhibitors vs TNF antagonists
Outcome: Risk of serious infections, malignant neoplasms, MACEs, or VTE

Methodological detailshead-to-head comparative effectiveness studies, random-effects meta-analysis, PRISMA, Newcastle-Ottawa Scale risk of bias

Head-to-head comparative effectiveness studies
Random-effects meta-analysis
PRISMA
Newcastle-Ottawa Scale risk of bias

Pooled result

Serious infections

Pooled hazard ratio

1.05

95% CI 0.97–1.13

By group

JAK inhibitors3.79IR · 95% CI 2.85–5.05 · per 100 person-years

TNF antagonists3.03IR · 95% CI 2.32–3.95 · per 100 person-years

JAK inhibitorsvs TNF antagonists

pooled HR 1.05 (95% CI 0.97–1.13)

As reported in the abstract

Further pooled results

IR, per 100 person-years

Outcome	JAK inhibitors	TNF antagonists		Pooled HR (95% CI)
Malignant neoplasms (primary outcome component)	1.00 (95% CI 0.77–1.31)	0.94 (95% CI 0.72–1.22)	0.512	1.02 (0.90–1.16)
MACEs (primary outcome component)	0.72 (95% CI 0.56–0.92)	0.66 (95% CI 0.49–0.89)	0.512	0.91 (0.80–1.04)
VTE (primary outcome component)Slightly higher risk with JAK inhibitors	0.57 (95% CI 0.40–0.82)	0.52 (95% CI 0.37–0.73)	0.512	1.26 (1.03–1.54)
			0.512Pooled hazard ratio (log scale)

Original publication

Comparative Safety of JAK Inhibitors vs TNF Antagonists in Immune-Mediated Inflammatory Diseases: A Systematic Review and Meta-Analysis. JAMA Netw Open. Published 2 September 2025. doi:10.1001/jamanetworkopen.2025.31204

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