INTRODUCTION
Discoid lupus erythematosus (DLE) is a chronic inflammatory skin disease that occurs with or without systemic lupus erythematosus (SLE). DLE treatment is challenging, and there is paucity of effective therapeutic options for patients with recalcitrance or intolerance to conventional therapies. Interferon-associated Janus Kinase (JAK) activation is considered a key mediator in lupus, highlighting the potential therapeutic role of JAK inhibitors.1 We evaluated the efficacy and safety of oral tofacitinib, a JAK inhibitor currently approved for the treatment of psoriatic arthritis, rheumatoid arthritis, polyarticular course juvenile idiopathic arthritis, ankylosing spondylitis, ulcerative colitis, in adult patients with active DLE with or without concurrent SLE.
Here, we describe the results of a 24-week, open-label, single-center pilot study of five patients with DLE, including 1 with concurrent SLE treated with 5 mg oral tofacitinib administered twice daily. All had biopsy-proven DLE for > 6 months, DLE covering > 5% of body surface area (BSA) or SLE with DLE covering > 2% of BSA, and Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) score > 8 at baseline. Inclusion criteria are detailed in Supplementary Table 1. The primary endpoint was an improvement in CLASI activity (CLASI-A) score at week 24, a validated score for cutaneous lupus erythematosus (CLE) severity. A four-point or 20% decrease in CLASI-A score was identified as minimal clinically significant improvement. However, a 6-point decrease or 50% reduction in CLASI-A reflects an important change.2 Quality of life (QoL) was assessed using Skindex-29, a validated skin-specific QoL survey.3 Other endpoints are summarized in Table 2. Study visits occurred every 2-4 weeks, during which clinical and safety parameters were evaluated. This study was approved by Tufts Institutional Review Board and registered with ClinicalTrials.gov (NCT03159936).
Patient characteristics are described in Table 1. Five patients (4 females) with a mean age of 47.6 years were enrolled. Three of five patients completed the study. One was lost to follow-up (#2) and one early terminated (#3) due to flaring of established psoriasis. The average disease duration was 7.8 years, and all patients had failed or were intolerant to topical steroids and antimalarials. Three patients received combination therapy with hydroxychloroquine. Assessments and outcomes are described in Table 2. Two patients showed improvement in DLE by week 24 with a 75% reduction in CLASI-A score (#1, #5), and two showed minimal response with a 30% reduction (#2, #4). Patient #3 showed only 13% reduction in CLASI-A, which was assessed at week five due to early termination. Only one patient had concurrent SLE (#1), which was non-responsive based on SLE Responder Index (SRI). Three patients had scalp involvement, and those who completed the study (#1, #5) experienced 100% and 65% hair regrowth, respectively. Three patients (#2, #4, #5) experienced a decrease in their Skindex-29 score with a 22%, 47%, and 38% reduction, respectively whereas two patients had an increase in Skindex-29 scores. None of the subjects achieved a Physician’s Global Assessment (PGA) of clear and almost clear (0-1). Mild to moderate adverse events (AEs) occurred in four patients (Table 2). No serious AEs were observed.
To date, no drug has been approved for the treatment of DLE.1 In a phase II trial, baricitinib, a JAK1/2 inhibitor, improved the proportion of patients with SLE achieving resolution of arthritis or rash; however, this effect was mainly due to joint improvement, whereas skin severity as measured by CLASI did not improve.4 Recently it was announced that baricitinib development for lupus treatment was discontinued after one phase 3 study met and one phase 3 study did not meet the primary endpoint of SRI-4 response.5 Tofacitinib has demonstrated promising results in treating cutaneous features of SLE.6 A recent case series described three patients with recalcitrant CLE who responded to tofacitinib with CLASI improvement of more than 4 points.7 The improvement observed in two of our participants further supports the role of JAK in CLE pathogenesis. Study limitations include a small sample size, lack of a control group, and concurrent use of other treatments. Randomized, placebo-controlled, dose-ranging trials with a larger number of patients are required to further determine the efficacy of JAK inhibitors in DLE.
