Tofacitinib in Combinazione con Metotrexato in Pazienti con Artrite Reumatoide: Efficacia Clinica, Risultati Radiografici e di Sicurezza dallo Studio di Fase 3 di 24 Mesi ORAL Scan
Arthritis Rheumatol. 2019 Jun;71(6):878-891RA patients receiving TOF 5 or 10 mg BID plus MTX showed sustained clinical and radiographic treatment effects through months 12-24. The safety profile was consistent with previous TOF studies. The 12-month data from the ORAL Scan study have been previously reported. This report assesses durability of responses, including structural damage progression, and safety with TOF through 24 months. Patients were randomized 4:4:1:1 to receive TOF 5 or 10 mg BID, or PBO advanced to TOF with stable, background MTX, at month 3 or 6. Clinical efficacy, structural progression, and TEAEs were evaluated. Analysis was performed on the full set with observed or non-responder imputation with no advancement penalty (NRINAP) for clinical efficacy and imputation by linear extrapolation for structural progression. NRINAP also addressed missing ACR responses, remission, and LDA. Clinical efficacy was maintained through months 12-24 for both TOF doses for ACR20/50/70 responses (with values that were significantly improved compared to baseline with each treatment), patients achieving remission or LDA, Improvements from baseline in DAS28-4(ESR), patients with CDAI and SDAI defined remission and Boolean-based remission. TOF patients had similar minimal progression of structural damage compared to baseline modified Total Sharpe Score, erosion scores and joint space narrowing. Patients advancing from PBO to TOF treatment sequences achieved similar clinical responses to those who received initial TOF treatment. Safety events were similar in type and frequency for both TOF doses, consistent with those previously reported. This study demonstrated maintenance of efficacy with TOF in patients with initial responses, including limited structural damage. No new safety signals emerged compared with the initial 12-month report or with previous clinical RCTs with TOF.