van Tuyl LH et al. (2008) Tight control and intensified COBRA combination therapy in early rheumatoid arthritis: 90% remission in a pilot trial. Ann Rheum Dis [doi:10.1136/ard.2008.090712]

Aggressive, high-dose combination therapy in early rheumatoid arthritis (COBRA) is superior to monotherapy for suppressing radiologically visible progression and inducing rapid remission in patients with rheumatoid arthritis (RA). In a study by van Tuyl and colleagues, treatment with a tightly controlled, intensified COBRA regimen resulted in a 90% rate of remission in 21 patients with RA. This remission rate exceeds the highest previously reported for early RA treatment (68% at 1 year).

The COBRA schedule comprised hydroxychloroquine (400 mg per day), sulfasalazine (2 g per day), methotrexate (10 mg per week) and high-dose prednisolone (60 mg per day tapered to 7.5 mg per day). After 8 and/or 21 weeks, treatment could be intensified if either 28-joint Disease Activity Score or levels of a marker of cartilage degradation remained above target. Treatment intensification at 8 weeks involved an increase in methotrexate dosage to 25 mg per week and, if targets were still not met, the option to add infliximab at 21 weeks. The methotrexate dose was increased in 10 patients, and infliximab was added to the regimen of 6 of these patients. Remission, defined as 28-joint Disease Activity Score <2.6, was achieved in 57% of patients at 8 weeks, 76% at 21 weeks and 90% at 40 weeks (the end of the study protocol).

As the authors suggest, this high remission rate probably relates to the tightly controlled and intensified COBRA regimen used in this study. This study was hampered by its small sample size and open-label design, but further studies in larger groups of patients with RA are clearly warranted.