Safety and Efficacy of Tofacitinib vs Methotrexate in the Treatment of Psoriatic Arthritis

Background:

Methotrexate, an anti-folate drug, is a widely accepted and commonly used DMARD for the treatment of PsA. Tofacitinib is a JAK inhibitor, and relatively new drug for this condition.

Aims:

To assess and compare safety and efficacy of Tofacitinib and Methotrexate in the treatment of PsA.

Methodology:

This open label, randomized, prospective study was conducted in Department of Rheumatology, BSMMU, Dhaka for 1½ years from September, 2017 to February, 2019. 61 patients, aged >18 years with the diagnosis of PsA for ≥3 months were randomized into two groups. 29 patients (Tofacitinib 5mg BD) and 32 patients (MTX from 15 mg/week to 25 mg/week over 1 month) were enrolled and followed-up at the end of 1, 3 and 6 months. Primary endpoint was ACR 20 response at the end of 3 months. Patients who achieved treatment target on the basis of DAPSA score at the end of 3 months were allowed to continue previuos treatment and assessed for safety and efficacy till 6 months. Patients not achieving treatment target in Tofacitinib group were put on Tofacitinib 10 mg BD and in MTX group were put on Tofacitinib 5 mg BD. These patients were followed-up for safety and efficacy at the end of 6 months. Secondary outcome measures were EULAR response, 66/68 joints SJC/TJC, VAS for pain, ESR, CRP, DAPSA, DAS28, PASI, PASI 75 response, MASES and HAQ-DI. Safety assessment was done on the basis of clinical history, examination and laboratory findings at each follow-up. Ethical clearance was obtained from IRB, BSMMU at the beginning. Statistical analysis was done using chi-square test, Fisher's exact test, paired sample t-test and independent sample t-test. Missing data were dealt with intention to treat (ITT) analysis.

Inclusion criteria

• Male or female patients more than 18 years
• Psoriatic arthritis > 3 months with peripheral involvement diagnosed on the basis of CASPAR criteria
• Unresponsive to more than 2 NSAIDs at maximum recommended doses for more than 4 weeks, i.e 2 weeks for each NASID

• Patients with active disease 6. PsA with or without extra-articular features like enthesitis, dactylitis and nail changes

Exclusion criteria

• Systemic infections requiring hospital admission during the past 6 months
• A history of active infectious disorders (including active or latent tuberculosis), and/or a history of chronic or recurrent serious infective diseases, opportunistic infections
• Hemoglobin (Hb) < 9 g/dl
• White blood cell count < 3000, Neutrophil count < 1000, Platelet count < 100000
• Live vaccines within 3 months prior to the first dose
• Serum creatinine > upper limit of normal reference range
• GFR less than 50 mL/min
• Alanine aminotransaminase (ALT) more than 2 times of ULN
• Pregnant or breast feeding, females of child-bearing potential not using highly effective contraception
• New York Heart Association Class III and IV congestive heart failure
• Evidence or history of malignancy, with the exception of adequately treated or excised non-metastatic basal or squamous cell cancer of the skin or cervical carcinoma in situ
• Any lymphoproliferative disorder, history of lymphoma, leukemia, or signs and symptoms suggestive of current lymphatic disease