medwireNews: An evaluation of the temporal effects of tofacitinib on lymphocyte counts suggests that monitoring of absolute lymphocyte count (ALC) alone is sufficient to minimize the risk for serious infection in patients with rheumatoid arthritis (RA).
The findings were derived from an analysis of phase III trials and phase I, II, and III long-term extension studies from the tofacitinib development program that included a total of 7061 patients with up to 117 months of follow-up data.
The researchers report that ALCs increased during the first month of treatment with the oral Janus kinase inhibitor, versus pretreatment baseline, but then gradually declined until 48 months.
At 48 months, the median ALC was approximately 24% below the baseline level, and although ALCs were stable from this point onwards, at around 400 cells/mm3 below baseline, 80 patients (80% on combination therapy, 20% on tofacitinib monotherapy) still experienced a confirmed value of less than 500 cells/mm3.
However, 3–6 weeks after discontinuing tofacitinib 70 (93%) of 75 of these patients achieved an ALC at or above 500 cells/mm3.
The researchers also found that CD3+, CD4+ and CD8+ T-cell counts decreased over time, with levels 21–28% lower at the end of the long-term follow-up period than at baseline.
B-cell counts appeared to increase in the short-term but were similar to baseline levels in the mid- to long-term, whereas natural killer cell counts decreased substantially in the short-term (up to 41%) but were then 70% higher than baseline at long-term follow-up.
In addition, 54.5%, 42.3%, and 70.6% of patients who had CD3+, CD4+, or CD8+ T-cell values, respectively, below the RA reference range at 50 months fell back within range following 4 weeks of tofacitinib withdrawal.
When the team looked at the incidence of serious infections among the patients, they found the highest rate among those with an ALC below 500 cells/mm3, at 7.1 per 100 person–years. The rate was 4.0 per 100 person–years for patients with an ALC of at least 500 but less than 750 cells/mm3 and 2.3–2.6 per 100 person–years among those with an ALC at or above 750 cells/mm3.
There was good correlation (R=0.65–0.86) between ALC and CD3+, CD4+, and CD8+ T-cell counts, but little correlation between the lymphocyte subset counts (LSC) and the rate of serious infection, suggesting that “additional measurement of LSC would not add value over and above ALC to minimize risk of infection,” Lisy Wang (Pfizer Inc, Cambridge, Massachusetts, USA) and co-authors remark in Arthritis & Rheumatology.
The team concludes: “Laboratory and safety outcomes related to immune function continue to be evaluated within the tofacitinib development program.”
By Laura Cowen
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