OBJECTIVES:We investigated whether the effectiveness of upadacitinib in rheumatoid arthritis (RA) treatment is affected by baseline CRP levels in a real-world setting.METHODS:UPwArds was a prospective, non-interventional study. Patients had moderate-to-severe RA and an inadequate response or intolerance to ≥1 disease-modifying anti-rheumatic drug (DMARD). The primary endpoint was clinical remission (Clinical Disease Activity Index [CDAI] ≤2.8) at 6 months. Secondary endpoints at 12 months included clinical remission and low disease activity assessed by CDAI and Simple Disease Activity Index criteria, DAS28-CRP <2.6/≤3.2, and patient-reported outcomes. The impact of baseline CRP levels (normal vs. above the upper limit of normal [ULN]) on primary and secondary endpoints was evaluated. The effect of concomitant MTX and prior inadequate response to biologic or targeted synthetic DMARDs (b/tsDMARD-IR) on the effectiveness of upadacitinib was also assessed. Safety was evaluated through 12 months.RESULTS:518 patients were included in the effectiveness analyses. At 6 months, 24.4% of patients achieved the primary endpoint (CDAI ≤2.8). At 12 months, similar proportions of patients with normal CRP and CRP above the ULN at baseline achieved CDAI ≤2.8 (27.3% and 29.1%) and other key secondary endpoints. The effectiveness of upadacitinib was comparable with and without concomitant MTX and in b/tsDMARD-naive and b/tsDMARD-IR patients. The safety results were consistent with the known safety profile of upadacitinib; no new safety signals were identified.CONCLUSIONS:Upadacitinib therapy was effective for RA in a real-world setting. Baseline CRP levels had no significant impact on the effectiveness of upadacitinib.

During the last decade cyclosporin A (CsA)-well-established in human transplantation-has been increasingly used in clinical studies for autoimmune diseases. CsA proved to be an effective treatment for rheumatoid arthritis (RA) in several placebo-controlled studies as well as in comparison with other DMARD (d-penicillamine, azathioprine, injectible gold). The evolution of CsA in RA includes increasing evidence that it is capable of retarding joint destruction and an effective partner in combination therapy with methotrexate and chloroquine. Effectiveness has also been shown in open clinical studies in systemic lupus erythematosus, psoriatic arthritis and adult Still's syndrome. The well-known risks of CsA therapy including renal toxicity and hypertension have been reduced by establishing and strictly using dosage and monitoring guidelines (starting dose 2.5-3 mg/kg/day, maximum dose 5 mg/kg, dosage reduction if serum creatinine rises>30% above baseline) with toxicity rate now corresponding to other highly effective DMARD, e.g. methotrexate. By using a new microemulsion formulation former pharmacokinetic variability has been reduced and bioavailability increased.