In patients with rheumatoid arthritis (RA) being treated with tofacitinib, absolute lymphocyte count (ALC) monitoring can adequately assess infection risk, according to a study published in Arthritis & Rheumatology.
The study included data on ALC from participants in phase 3 (12 to 24 months) and phase 1, 2, and 3 long-term extension studies of tofacitinib. Researchers included data on lymphocyte subset counts (LSCs) from phase 2 studies (1.5 to 6 months), an ORAL Sequel vaccine substudy (22 months), and an ORAL Sequel lymphocyte substudy (50 months) of tofacitinib.
The researchers evaluated the reversibility of ALC/LSC changes and analyzed the relationship of ALC and LSC in the RA population.
The results indicated that participants treated with tofacitinib had an initial increase in ALC at 1 month compared with baseline. At 12 months, participants showed median decreases in ALC from baseline of -190 cells/mm3 with twice-daily tofacitinib 5 mg plus methotrexate, and -310 cells/mm3 with twice-daily tofacitinib 10 mg plus methotrexate.
Gradually, the ALCs declined to a steady state of -400 cells/mm3 after approximately 48 months, for a median decrease of approximately 24%.
Over long-term treatment, participants had decreases in CD4+ and CD8+ T-cell counts. After stopping treatment, the researchers found that ALC and LSC changes were reversible, and that 93% of participants with follow-up data achieved ALC ≥500 cells/mm3 after a median of 3 to 6 weeks after discontinuing treatment.
Participants with ALC <500 cells/mm3 had an increased risk for serious infections.
The researchers did not find any significant associations between serious infection rates and CD4+ T-cell, CD8+ T-cell, B cell, or natural killer cell counts.
“From a clinical perspective, evaluation of ALC at baseline and monitoring every 3 months during treatment is recommended,” the researchers wrote. “Initiation of tofacitinib is not recommended in patients with ALC <500 cells/mm3, and those developing this during treatment should discontinue tofacitinib therapy.”
This study was sponsored by Pfizer, Inc. Please see original article for a full list of author disclosures.
van Vollenhoven R, Lee EB, Strengholt S, et al. Evaluation of the short-, mid-, and long-term effects of tofacitinib on lymphocytes in patients with rheumatoid arthritis [published online November 14, 2018]. Arthritis Rheumatol. doi:10.1002/art.40780