key: cord-0859507-zhiehtf3
authors: Curtis, Jeffrey R; Johnson, Sindhu R; Anthony, Donald D; Arasaratnam, Reuben J.; Baden, Lindsey R.; Bass, Anne R.; Calabrese, Cassandra; Gravallese, Ellen M.; Harpaz, Rafael; Kroger, Andrew; Sadun, Rebecca E.; Turner, Amy S.; Williams, Eleanor Anderson; Mikuls, Ted R.
title: Reply to Commentary on the ACR “COVID‐19 Vaccine Clinical Guidance Summary for Patients with Rheumatic and Musculoskeletal Diseases”
date: 2021-05-27
journal: Arthritis Rheumatol
DOI: 10.1002/art.41805
sha: ddaa6fab8dd1c531c5cae643b49070eefc0c7f7c
doc_id: 859507
cord_uid: zhiehtf3

We appreciate the letter by Mortezavi et. al. describing vaccine response and the frequency of disease worsening in patients receiving tofacitinib. The ACR COVID Vaccine Guidance Task Force was aware of the two studies cited and appreciate their summary of the results. We would point out that in the rheumatoid arthritis study by Winthrop et. al., patients receiving tofacitinib in Study A had a lower likelihood of a satisfactory response to pneumococcal vaccination (45.1%) compared to placebo‐treated patients (68.4%), a difference of 23.3%, 95% CI −36.6 to −9.6%. The differences were numerically even larger for patients receiving concomitant tofacitinib and methotrexate (31.6% of patients with a satisfactory response, difference of −30.2%, 95% CI −47.3 to −11.4%) compared to methotrexate monotherapy.

difference of 23.3%, 95% CI −36.6 to −9.6%. The differences were numerically even larger for patients receiving concomitant tofacitinib and methotrexate (31.6% of patients with a satisfactory response, difference of −30.2%, 95% CI −47.3 to −11.4%) compared to methotrexate monotherapy. Our challenge was in considering the appropriateness of extrapolating results from vaccine studies of influenza, pneumococcal, and tetanus toxoid to make inferences regarding the anticipated response to vaccination against SARS-CoV-2, a novel antigen to which most individuals have not previously been exposed. The task force recognized that infection rates, and perhaps response to vaccinations against those infections, might be heterogeneous by pathogen. For example, janus kinase inhibitors (JAKi) approximately double the incidence of herpes zoster compared to biologics such as tumor necrosis factor inhibitors, yet they do not meaningfully increase rates of other infections (e.g., pneumonia) 1,2,3 . We noted that in the Oral Strategy study, adalimumab-treated patients receiving vaccination with the live herpes zoster vaccine had lower incidence rates (IR) of herpes zoster (0.0 per 100 patient-years [py]) compared to non-vaccinated patients (IR 2.1 per 100py). In contrast, and

This article is protected by copyright. All rights reserved recognizing that numbers were small, tofacitinib-treated patients had similar rates of herpes zoster regardless of vaccination (IR 3.0 per 100py in vaccinated vs. 2.2 per 100py in unvaccinated patients) 4 .

We also appreciate the data provided by Mortezavi et. al. regarding the rate of disease worsening in patients who briefly interrupt tofacitinib. At approximately two weeks, the mean worsening in the DAS28-4 of 0.7 units is of smaller magnitude than typically considered the minimally important difference (MID) for the DAS28 (i.e., greater than 1.2 units) 5 . The MID for disease worsening of the CDAI for patients starting in moderate disease activity is undefined 6 , although a 1 unit change in each of the 4 CDAI components (TJC, SJC, patient global, and physician global) is often considered to be the measurement error for each of these.

Taken together, the mean amount of disease worsening associated with brief interruptions in therapy seems small and likely not of clinical importance for most patients, especially in light of the guidance to hold JAKi for one week at the time of each vaccine administration, rather than for two consecutive weeks.

Ultimately, we await prospective data regarding the influence of JAKi and other immunomodulatory therapies used at the time of COVID vaccination on immunogenicity and correlates of serologic protection. Since the ACR COVID Vaccine Guidance is a living document, our plan is to rapidly update it and incorporate new evidence as it accumulates.

Herpes Zoster and Tofacitinib: Clinical Outcomes and the Risk of Concomitant Therapy

Arthritis Rheumatol

A systematic review and meta-analysis of infection risk with small molecule JAK inhibitors in rheumatoid arthritis

Real-world comparative risks of herpes virus infections in tofacitinib and biologic-treated patients with rheumatoid arthritis

Live Zoster Vaccine in Patients With Rheumatoid Arthritis Treated With Tofacitinib With or Without Methotrexate

Adalimumab With Methotrexate: A Post Hoc Analysis of Data From a Phase IIIb/IV Randomized Study

Test-retest reliability of disease activity core set measures and indices in rheumatoid arthritis

Determining the Minimally Important Difference in the Clinical Disease Activity Index for Improvement and Worsening in Early Rheumatoid Arthritis Patients

Accepted Article