Pharmacokinetics, effectiveness, tolerability and effect on quality of life of open-label tofacitinib for the treatment of moderately active mucocutaneous manifestations of SLE: results of a 76-week phase II study.
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OBJECTIVE: To investigate the pharmacokinetics, effectiveness, safety and tolerability of tofacitinib in young adults with active mucocutaneous (MC) SLE manifestations. METHODS: Patients with SLE and Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) Activity (CLASI-A) Scores >8 newly received open-label tofacitinib from baseline to week (week) 72. Intensive pharmacokinetics sampling was done at the end of week 1, and safety was assessed throughout the study. The primary effectiveness endpoint was partial response of MC activity defined as <20% improvement of the CLASI-A Score from baseline (CLASI-PR) at week 8 in intention-to-treat analysis; secondary and other endpoints included MC complete response (CLASI-CR; CLASI-A=0) and quality of life (QoL) as measured by Skindex-29. RESULTS: Subjects were 11 patients (female patients: 10, mean±SD age: 23.0±5.87 years) with moderate to severe MC manifestations (CLASI-A=16.6±8.03). The pharmacokinetics of tofacitinib was comparable to that seen in juvenile and adult arthritis. During 629 patient-weeks of follow-up, 73 adverse events (AEs) were reported, none of which were considered severe or led to study discontinuation. There were three serious AEs (pelvic inflammatory disease, appendicitis and migraine with aura) but no major cardiovascular events, malignancies or death. In intention-to-treat analysis, at week 8 CLASI-PR was achieved in 73% (8/11) of subjects, in 82% at week 24 and 100% at week 72, respectively. Although CLASI-A Scores significantly decreased from baseline (baseline/week 8/week 24/week 72=16.55±8.03/8.64±7.8/8.82+7 .9/7+9.7; p<0.001), CLASI-CR was achieved by only <10% (1/11), starting week 8. Skindex-29 Scores improved significantly as early as week 4 (baseline/week 4/week 24/week 72= 37.6±24.16/26.1±23.58/24.3±28.67/25.5±30.71; p=0.009). CONCLUSION: Tofacitinib in patients with SLE with active MC manifestations showed good effectiveness by week 4 as well as tolerability at exposure comparable to those with other rheumatic diseases. Tofacitinib was associated with significant improvement of QoL due to rapid improvement of MC inflammation. Observed safety and pharmacokinetics were comparable to observations in juvenile and adult arthritis.