Tight control and intensified COBRA combination treatment in early rheumatoid arthritis: 90% remission in a pilot trial.
OBJECTIVE
To investigate the efficacy and feasibility of an intensive combination treatment in early rheumatoid arthritis (RA) combined with monitoring both disease activity and cartilage degradation.


METHODS
In a pilot trial, 21 patients with active early RA (mean DAS28 5.3; mean disease duration 3 months) were treated with COBRA treatment comprising sulfasalazine, methotrexate and high-dose step-down prednisolone, intensified by adding hydroxychloroquine and continued low-dose prednisolone. In addition, based on measurements of disease activity or a marker of cartilage degradation (CTX-II), treatment adjustments were possible with methotrexate intensification after 8 or 21 weeks; and with infliximab after 21 weeks.


RESULTS
Nineteen of 21 patients (90%) were in remission (DAS28 <2.6) after 40 weeks (8 weeks, 57%; 21 weeks, 76%). American College of Rheumatology (ACR) criteria, ACR20, 50, 70 and 90 improvements rates were 100%, 95%, 71% and 43% respectively. CTX-II excretion decreased by mean (SD) 347(292) ng/mmol creatinine, but only 50% of patients reduced their CTX-II excretion below the cut-off point. The two monitoring groups showed no significant difference in remission according to DAS score or CTX-II excretion, despite a trend towards more intensive treatment in the CTX-II group. Treatment intensification was feasible according to protocol.


CONCLUSIONS
This small pilot study suggests that intensified and tightly controlled COBRA treatment is uniquely effective in early RA.


BACKGROUND
ISRCTN96372677.
van Tuyl
L H D
LH
Department of Clinical Epidemiology & Biostatistics, VU University Medical Center, Amsterdam, The Netherlands. L.vantuyl@vumc.nl
Lems
W F
WF
Voskuyl
A E
AE
Kerstens
P J S M
PJ
Garnero
P
P
Dijkmans
B A C
BA
Boers
M
M
D000328:Adult; D000368:Aged; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000652:urine; D015415:Biomarkers / Q000652:urine; D024043:Collagen Type II / Q000652:urine; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D006886:Hydroxychloroquine / Q000627:therapeutic use; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use; D008875:Middle Aged; D010865:Pilot Projects; D011239:Prednisolone / Q000627:therapeutic use; D012074:Remission Induction; D012720:Severity of Illness Index; D012460:Sulfasalazine / Q000627:therapeutic use; D016896:Treatment Outcome
D018501:Antirheumatic Agents; D015415:Biomarkers; D024043:Collagen Type II; D012460:Sulfasalazine; D006886:Hydroxychloroquine; D011239:Prednisolone; D008727:Methotrexate