TY - JOUR T1 - Response to: Correspondence on “Associations of baseline use of biologic or targeted synthetic DMARDs with COVID-19 severity in rheumatoid arthritis” by Sparks <em>et al</em> JF - Annals of the Rheumatic Diseases JO - Ann Rheum Dis DO - 10.1136/annrheumdis-2021-220960 SP - annrheumdis-2021-220960 AU - Zachary S Wallace AU - Jeffrey A Sparks AU - Philip C Robinson AU - Pedro M Machado AU - Jinoos Yazdany Y1 - 2021/08/22 UR - http://ard.bmj.com/content/early/2021/08/22/annrheumdis-2021-220960.abstract N2 - We appreciate the interest in our paper1 and the opportunity to provide additional clarification and context. It is now generally accepted that there are different phases of COVID-19 illness.2 Our study investigated baseline use, presumably at the earliest phase of infection where viral replication is most pronounced. Clinical trials have typically tested the efficacy of medication use among hospitalised patients where pathologic hyperinflammation may mediate poor clinical outcomes. Therefore, the timing of immunomodulator use related to the COVID-19 disease course may have different effects on clinical outcomes, and trial results may not be able to be extrapolated to observational studies of baseline medication use.Observational results may lend insight into key immune mechanisms that could alter the trajectory of COVID-19, but the results could be confounded. To limit possible confounding by indication, our study used an active comparator study design that included patients with a single disease, rheumatoid arthritis (RA), who were taking biologic or targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARD).1 In doing so, we included patients with similar disease severity who had the opportunity to receive advanced therapy. We compared each class of b/tsDMARD to tumour necrosis factor inhibitors (TNFi) since this was the most commonly used b/tsDMARD. Of note, medications were collected by mechanism of action, rather than individual drugs. While this observational study design minimised possible confounding, all patients were on some immunomodulator regimen, so it is possible that some of these medications might have had favourable effects on the COVID-19 disease trajectory.We agree that our finding associating rituximab for use in RA with worsened COVID-19 severity compared with TNFi use1 has biologic plausibility due to the importance of the adaptive immune response to infections and to SARS-CoV-2 in particular. A previous GRA study also associated rituximab use with increased COVID-19-related … ER -