Associations of baseline use of biologic or targeted synthetic DMARDs with COVID-19 severity in rheumatoid arthritis: Results from the COVID-19 Global Rheumatology Alliance physician registry
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  • Published on:
    Could discontinuing JAKi’s in the event of SARS-CoV-2 infection be harmful?
    • Ronald F. van Vollenhoven, Professor and Chair Amsterdam UMC and Amsterdam Rheumatology Center
    • Other Contributors:
      • Sander W. Tas, Rheumatologist
      • Michael Nurmhomed, Professor of rheumatology

    Sparks et al. (1) are to be congratulated on an important and timely study. They found that the use of JAKi was associated with worse outcome of Covid-19 infection, and they interpret this as a harmful effect of the treatment in that particular setting. But this question deserves further consideration. Assuming that the observation is correct, what could the mechanism be? As the authors correctly point out, some JAKis did show benefits for patients with severe Covid-19 infection (2, 3). We therefore propose an alternative explanation of the observed data.

    Some guidance documents (4,5), and certainly medical practice traditions, frequently have patients discontinue immunomodulatory treatments when a potentially severe infection is diagnosed, and it seems safe to assume that the vast majority of patients in the study did, in fact, stop their treatment when they became aware of the infection. While this would of course apply to all antirheumatic therapies, there are important differences in the impact this might have. Biologicals have half-lives in the order of weeks, and the effect of stopping the treatment is therefore limited in the acute setting. For MTX, pharmacodynamic aspects also lead to a long latency in the impact of discontinuing the drug. In contrast, JAKi have short half-lives and discontinuing the treatment will almost immediately lead to the re-activation of the relevant signaling pathways.

    We therefore propose, as an alternative possible explan...

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    Conflict of Interest:
    RV: AbbVie, AstraZeneca, Biogen, Biotest, BMS, Galapagos, Gilead, GSK, Janssen, Lilly, Pfizer, Roche, Sanofi, Servier, UCB, Vielabio