What other Janus kinase (JAK) inhibitors are similar to upadacitinib (Rinvoq) for rheumatoid arthritis?

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Last updated: September 29, 2026 • View editorial policy

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JAK Inhibitors Similar to Rinvoq (Upadacitinib) for Rheumatoid Arthritis

The other JAK inhibitors approved for rheumatoid arthritis that are similar to upadacitinib (Rinvoq) include tofacitinib, baricitinib, filgotinib (in Europe/Japan), and peficitinib (in Japan), all of which demonstrate comparable efficacy as a class, though upadacitinib shows numerically higher response rates in head-to-head comparisons. 1, 2

Available JAK Inhibitors

The currently approved JAK inhibitors for RA include:

  • Tofacitinib (JAK1/JAK3 preferential)
  • Baricitinib (JAK1/JAK2 preferential)
  • Upadacitinib (JAK1 selective)
  • Filgotinib (JAK1 selective) - approved in Europe and Japan 1
  • Peficitinib (pan-JAK) - approved in Japan 1, 2

Comparative Efficacy

While EULAR guidelines state that bDMARDs and tsDMARDs (including all JAK inhibitors) have similar average efficacy with no clear preference among them 2, more recent evidence suggests upadacitinib demonstrates numerically superior outcomes:

  • At 12 weeks, upadacitinib 15 mg + csDMARD achieved the highest ACR50 response (43.4%) compared to tofacitinib 5 mg (38.7%), baricitinib 2 mg (37.1%), and baricitinib 4 mg (36.7%) 3
  • Clinical remission rates (DAS28-CRP <2.6) at week 12 were highest with upadacitinib (29.8%), followed by tofacitinib (24.3%), baricitinib 4 mg (22.8%), and baricitinib 2 mg (20.1%) 3
  • Real-world data from 2026 showed patients on upadacitinib were significantly more likely to achieve physician-reported remission (54.3% vs 44.1%, p=0.030) and have no pain (43.4% vs 32.8%, p=0.016) compared to other JAK inhibitors 4

Important caveat: These differences were not statistically significant in network meta-analysis, and the clinical relevance of small numerical differences remains uncertain 2, 3.

Safety Profile Considerations

All JAK inhibitors share a class-wide safety profile that includes:

  • Increased risk of herpes zoster (all agents) 2, 5
  • Venous thromboembolism (VTE) - particularly concerning with tofacitinib 10 mg twice daily and baricitinib 4 mg, also observed with upadacitinib 2
  • Major adverse cardiovascular events (MACE) - data primarily from tofacitinib safety study 2
  • Malignancy risk - increased lymphomas and lung cancers noted in long-term tofacitinib data 2

Critical risk stratification: Avoid or use with extreme caution in patients with:

  • Prior history of VTE
  • Age >65 years (especially with cardiovascular risk factors)
  • High body mass index
  • Concurrent hormone replacement therapy 2

Specific Differences Between Agents

Hematologic Effects

  • Baricitinib causes significantly greater increases in platelet counts compared to tofacitinib or upadacitinib (OR 2.009, p=0.007) 6
  • All three agents reduce absolute neutrophil count similarly 6

Lipid Metabolism

  • Filgotinib shows the most favorable lipid profile with no change in LDL-C/HDL-C ratio after 12 months, while other JAK inhibitors increase atherogenic indices 5

Drug Survival

Real-world retention data (2026) shows:

  • Tofacitinib: 81.9% at 6 months, median survival 16.5 months
  • Baricitinib: 77.8% at 6 months, median survival 17 months
  • Upadacitinib: 69.6% at 6 months, median survival 11 months 7

However, upadacitinib was predominantly prescribed after failure of multiple therapies, making direct comparison difficult 7.

Practical Selection Algorithm

  1. First-line JAK inhibitor choice (after csDMARD failure with poor prognostic factors):

    • Consider upadacitinib 15 mg daily for highest probability of remission based on trial data 4, 3
    • Alternative: tofacitinib 5 mg twice daily (longest safety data: 9.5 years, 22,875 patient-years) 1

  2. If cardiovascular risk factors or age >65 years: Exercise extreme caution with all JAK inhibitors; consider biologics first 2

  3. If prior VTE or high thrombotic risk: Avoid JAK inhibitors entirely 2

  4. If lipid concerns predominate: Consider filgotinib (where available) for most favorable lipid profile 5

  5. If thrombocytopenia is a concern: Avoid baricitinib due to platelet-raising effects 6

Key Monitoring Pitfall

All JAK inhibitors that interfere with IL-6 signaling directly suppress CRP production, potentially masking true disease activity when using CRP-based instruments like DAS28-CRP 1. Use clinical assessment and non-CRP measures cautiously in these patients.

Regulatory Status

Do not combine upadacitinib (or any JAK inhibitor) with other JAK inhibitors, biologic DMARDs, or potent immunosuppressants like azathioprine or cyclosporine 8. This is an FDA-labeled contraindication across all indications.

References

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