tofacitinib and Skin-Ulcer

Systemic sclerosis (SSc) is a rare autoimmune connective tissue disease characterized by fibrosis of the skin and internal organs, autoimmunity-driven damage and vasculopathy. The current approved disease-modifying treatments have limited efficacy, and treatment is guided toward alleviating organ complications. Thus, there is an unmet need for discovering new effective treatment options. There is recent evidence that the JAK/STAT signaling pathway is markedly activated in SSc patients. To assess the efficacy and safety of tofacitinib (TOF) on skin and musculoskeletal involvement as compared to methotrexate (MTX) in systemic sclerosis (SSc). In this 52-week pilot study, 66 patients with SSc were enrolled: 33 patients received 5 mg of oral TOF twice a day; 33 received 10 mg of MTX weekly. The proportion of dcSSc and lcSSc patients was similar (dcSSc: 42% TOF group and 36% MTX group; lcSSc: 58% TOF group and 64% MTX group). The primary outcome was the change in the modified Rodnan skin score (mRSS). Secondary outcomes included ultrasound (US) skin thickness and musculoskeletal involvement (US10SSc score). Digital ulcers (DUs) and adverse events (AEs) were documented through the treatment. Both groups had similar characteristics and medians on the outcome measures at baseline. At week 52, the TOF median mRSS was significantly lower than the MTX (p < 0.001) with a mean reduction of 13 points versus MTX 2.57. The mean percent improvement in the TOF group was 44% higher than in the MTX group. TOF median US skin thickness was significantly lower than MTX (p < 0.001), with a mean reduction of 0.31 mm versus 0.075 mm in the MTX group. The US10SSc median score was significantly lower in the TOF group (p = 0.002); mean reduction of 10.21 versus 5.27 in the MTX group. Healing of DUs with no new occurrences was observed in the TOF group. There was no significant difference between the groups in the number of AEs from baseline to week 52. TOF showed greater efficacy than MTX in reducing mRSS, skin thickness and musculoskeletal involvement in SSc and a satisfactory safety profile.

Topics: Adult; Female; Humans; Immunosuppressive Agents; Male; Methotrexate; Middle Aged; Pilot Projects; Piperidines; Protein Kinase Inhibitors; Pyrimidines; Scleroderma, Systemic; Severity of Illness Index; Skin; Skin Ulcer; Ultrasonography

To date, there is no treatment with proven efficacy for cutaneous leukocytoclastic vasculitis (CLV). Several reports have suggested that CLV responds favorably to corticosteroids, colchicine, nonsteroidal anti-inflammatory drugs (NSAIDs), azathioprine, and hydroxychloroquine (HCQ). To the best of our knowledge, the oral small molecule Janus kinase inhibitor, tofacitinib, plays an important role in the treatment of autoimmune and inflammatory diseases. Therefore, tofacitinib may be a prospective therapy in patients with CLV.. A 29-year-old woman presented to our hospital with a 5-year history of symmetric skin lesions mainly affecting both lower extremities. The results for anti-neutrophil cytoplasmic antibodies (ANCA), anti-extracted nuclear antigens (ENA) autoantibodies, anti-double-stranded deoxyribonucleic acid (dsDNA) antibodies, and antinuclear antibodies (ANA) were all negative. The definite diagnosis of CLV was determined by a skin biopsy. However, the patient exhibited a poor response to prednisone, HCQ, methotrexate, colchicine, azathioprine, and tripterygium wilfordii polyglycoside tablets (TGTs) treatments. She was then treated with oral tofacitinib (5 mg twice daily) and oral prednisone (25 mg daily).. Her skin lesions gradually improved over a period of 4 weeks. Two months later, the skin ulcers completely resolved. No evidence of recurrence of skin ulcers was observed during a 6-month follow-up.. We present the first case of a female patient receiving short-term tofacitinib therapy for refractory CLV. Tofacitinib may be a promising oral alternative for patients with CLV. However, its efficacy and safety require further appraisal through clinical trials.

Topics: Adult; Drug Therapy, Combination; Female; Glucocorticoids; Humans; Janus Kinase Inhibitors; Piperidines; Prednisone; Pyrimidines; Skin Ulcer; Treatment Outcome; Vasculitis, Leukocytoclastic, Cutaneous; Wound Healing

Topics: Humans; Livedo Reticularis; Piperidines; Protein Kinase Inhibitors; Pyrimidines; Pyrroles; Skin Diseases, Vascular; Skin Ulcer; Vascular Diseases

Tofacitinib is a targeted inhibitor of janus kinase (JAK), currently approved for the treatment of rheumatoid arthritis. We present a patient on treatment withtofacitinib who had an episode of classic dermatomal herpes zoster followed months later by atypical chronic cutaneous ulcers also caused by herpes zoster.

Topics: Arthritis, Rheumatoid; Chronic Disease; Female; Herpes Zoster; Humans; Middle Aged; Piperidines; Protein Kinase Inhibitors; Pyrimidines; Pyrroles; Skin; Skin Ulcer