Combination treatment with methotrexate, cyclosporine, and intraarticular betamethasone compared with methotrexate and intraarticular betamethasone in early active rheumatoid arthritis: An investigator‐initiated, multicenter, randomized, double‐blind, parallel‐group, placebo‐controlled study

Abstract

Objective. To investigate whether disease control can be achieved in early active rheumatoid arthritis (RA) by treatment with methotrexate and intraarticular betamethasone, and whether the addition of cyclosporine to the regimen has any additional effect.Methods. Patients (n ‫؍‬ 160) were randomized to receive methotrexate 7.5 mg/week plus cyclosporine 2.5 mg/kg of body weight/day (combination therapy) or methotrexate plus placebo-cyclosporine (monotherapy). At weeks 0, 2, 4, 6, and 8 and every 4 weeks thereafter, betamethasone was injected into swollen joints (maximum 4 joints or 4 ml per visit). Beginning at week 8, if synovitis was present, the methotrexate dosage was increased stepwise up to 20 mg/week, with a subsequent stepwise increase in the cyclosporine or placebo-cyclosporine dosage up to 4 mg/kg. Results. At 52 weeks, 20% improvement according to the American College of Rheumatology criteria (ACR20) was achieved in 85% of the combination therapy group versus 68% of the monotherapy group (P ‫؍‬ 0.02). The median individual overall ACR response (ACR-N) in the 2 groups was 80.0% (interquartile range 40.1-91.8%) and 54.5% (interquartile range 2.4-87.8%), respectively (P ‫؍‬ 0.025). At 48 and 52 weeks, ACR remission criteria were met in 35% of the combination therapy group and 28% of the monotherapy group. Progression in the Larsen score at 52 weeks was -0.2 ؎ 6.5 and 0.4 ؎ 6.9 (mean ؎ SD) in the combination therapy and monotherapy groups, respectively. Serum creatinine levels increased by 7%, and hypertrichosis was more prevalent, in the combination therapy group. Conclusion. Combined treatment with methotrexate and intraarticular glucocorticoid showed excellentSupported by a grant from the Danish Rheumatism Association. Novartis Healthcare Denmark A/S kindly provided cyclosporine and placebo-cyclosporine and sponsored an independent good clinical practice monitor. Nycomed provided methotrexate, folic acid, and calcium/vitamin D. Schering-Plough provided injectable betamethasone. Merck, Sharp, & Dohme provided alendronate.

Cartilage Oligomeric Matrix Protein Associates Differentially with Erosions and Synovitis and Has a Different Temporal Course in Cyclic Citrullinated Peptide Antibody (Anti-CCP)-positive versus Anti-CCP-negative Early Rheumatoid Arthritis

“…A total of 160 patients with newly diagnosed untreated RA were included in the CIMESTRA trial 13 . Briefly, patients fulfilled the American College of Rheumatology (ACR) 1987 revised criteria for RA 14 .…”

To what extent is NICE guidance on the management of rheumatoid arthritis in adults being implemented in clinical practice? A regional survey

“…This recommendation was based on randomised controlled trials (RCTs) using combination DMARDs and glucocorticoids. 8,9,18 However, entry criteria to these trials differed so that some patients with less active RA received combination therapy. In the trials comparing combination therapy with monotherapy, glucocorticoid use was increased in the combination arm, which might explain the superiority of combination therapy.…”

New Recommendations for the Management of Rheumatoid Arthritis (Eular, 2013): The Role of Methotrexate

“…Особенностью протокола была возможность проведе-ния внутрисуставных инъекций триамцинолона в припух-шие суставы (максимально 4 сустава и не более 4 мл за ви-зит). Ранее, по данным той же группы авторов (исследова-ние CIMESTRA -CIclosporine, MEthotrexate and intraarticular STerroid in early Rheumatoid Arthritis), у пациентов с ран-ним РА агрессивная монотерапия МТ в комбинации с внут-рисуставным введением триамцинолона позволяет эффек-тивно контролировать активность заболевания и тормозит прогрессирование деструкции суставов в течение 5 лет на-блюдения [59][60][61] (см. табл.…”