Use of Tofacitinib in the Context of COVID‐19 Vaccination: Comment on the American College of Rheumatology Clinical Guidance for COVID‐19 Vaccination in Patients With Rheumatic and Musculoskeletal Diseases

To the Editor:

We read with great interest the American College of Rheumatology (ACR) clinical guidance for COVID‐19 vaccination in patients with rheumatic and musculoskeletal diseases (1). We commend the Task Force’s emphasis on the importance of immunization in this population and for providing guidance to the rheumatology community. Regarding their recommendation to withhold JAK inhibitors for 1 week after each COVID‐19 vaccine dose (1), we propose the following available tofacitinib data for consideration in this context.

Tofacitinib is a reversible JAK inhibitor characterized by rapid absorption and elimination and a short half‐life (2). The impact of tofacitinib on lymphocyte subsets consists of small and variable changes in T cell counts, increases in B cell counts, and decreases in natural killer (NK) cell counts. After drug discontinuation, B and NK cell counts can take from 2 to 6 weeks to return to baseline levels (2), which suggests that the impact of a 1‐week hold of tofacitinib on immune cell counts would likely be small.

Studies have also shown that T cell–dependent and T cell–independent vaccine responses are unaffected by tofacitinib (3, 4). In one study, patients with rheumatoid arthritis receiving treatment with tofacitinib 10 mg twice a day (with or without methotrexate) were randomized to continue or to stop tofacitinib treatment 1 week prior and 1 week following immunization with the pneumococcal polyvalent‐23 vaccine (PPV23) or the trivalent influenza vaccine (3). Antibody titers measured 35 days postimmunization were satisfactory in both the continue and hold groups for the PPV23 (75.0% and 84.6%, respectively [T cell–independent response]) and the influenza vaccine (66.3% and 63.7%, respectively [T cell–dependent response]) (3). In another study, patients with psoriasis receiving treatment with tofacitinib 10 mg twice a day demonstrated a robust vaccine response to T cell–dependent tetanus toxoid (88%) and T cell–dependent 13‐valent conjugate pneumococcal vaccines (80%) (4).

As with any clinical decision, risk–benefit analysis for each patient includes consideration of the potential for disease flares. In the aforementioned study, tofacitinib treatment interruption led to a steady increase in disease activity scores compared with continuous treatment () (5). Therefore, in addition to the ACR guidelines, we encourage clinicians to consider the above data during shared decision‐making with patients when advising on medication management in the context of COVID vaccination.

Figure 1.

Least squares (LS) mean changes from baseline in C‐reactive protein (CRP) levels (A), Disease Activity Score in 28 joints (4‐variable) using the erythrocyte sedimentation rate (DAS28‐4[ESR]) (B), and Clinical Disease Activity Index (CDAI) (C) over time during the sub‐study of the long‐term extension study, ORAL Sequel. Shaded areas indicate the dose‐interruption period. Baseline was defined as visit 1 of the sub‐study. ^aLS mean change (Δ) in continuous treatment group minus LS mean change in interrupted treatment group. bid = twice a day; 95% CI = 95% confidence interval. ** = P < 0.001; *** = P < 0.0001 for interrupted versus continuous treatment. Adapted from Figure 3 in Kaine et al (5) (available at https://link.springer.com/article/10.1007%2Fs10067-020-04956-1) by removing the original panel B from the figure; used under Creative Commons attribution 4.0 International (CC BY 4.0) at https://creativecommons.org/licenses/by/4.0/.

Editorial support, under the guidance of the authors, was provided by Tanya Guha, PhD, CMC Connect, McCann Health Medical Communications and was funded by Pfizer Inc, New York, New York, USA, in accordance with Good Publication Practice (GPP3) guidelines (Ann Intern Med 2015;163:461–4). Drs. Mortezavi, Menon, Lee, and Rivas are employees and shareholders of Pfizer Inc.