Inpatient treatment of rheumatoid arthritis with synacthen depot: a double blind placebo controlled trial with 6 month followup.
OBJECTIVE
To assess the additional benefit of synacthen depot over standard inpatient care for patients hospitalized with active rheumatoid arthritis (RA).


METHODS
All patients admitted to our unit with active RA without exclusion criteria were invited to participate and randomized to subcutaneous synacthen depot 0.5 mg on alternate days for 2 injections or 2 injections of saline. Patients, staff, and assessors of response were blinded to the intervention. Assessment [OMERACT set, American College of Rheumatology (ACR) global improvement, dose of intraarticular (IA) or intramuscular (IM) methylprednisolone] was performed at admission to hospital, at discharge, and at 3 and 6 months. Oral prednisone use constituted a protocol violation.


RESULTS
Of 137 patients with RA admitted over the period of recruitment, 36 (26%) were enrolled; 31 completed followup. There were no between-group differences in the change from admission of any individual disease activity measure at any time point. However, using a rigorous global response measure (ACR 50%), a difference was detected in favor of synacthen depot at discharge (52.6% of the intervention group improved vs. 17.6% of controls; p = 0.029, number-needed-to-treat 2.86). Patients treated with synacthen depot showed a trend toward more IA or IM corticosteroid between discharge and 3 months (mean dose 56 vs. 31 mg; p = 0.19) and a trend toward more patients requiring a change in slow acting antirheumatic drug after discharge (4 vs. 1; p = 0.27).


CONCLUSIONS
There is some additional benefit of synacthen depot in the hospital treatment of RA, but the effect is lost by 3 months, with a suggestion of rebound worsening in these patients. We postulate that oversuppression of corticotrophin releasing hormone by exogenous adrenocorticotrophic hormone in patients who already have a hypothalamic deficit may contribute to the rebound worsening of disease activity seen in these patients.
Taylor
W J
WJ
Wellington Regional Rheumatology Unit, Hutt Hospital, Hutt Valley Health Corporation, Lower Hutt, New Zealand. wtaylor@wnmeds.ac.nz
Rajapakse
C N
CN
Harris
K A
KA
Harrison
A A
AA
Corkill
M M
MM
D000893:Anti-Inflammatory Agents / Q000008:administration & dosage; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D003366:Cosyntropin / Q000008:administration & dosage*; D003692:Delayed-Action Preparations / Q000008:administration & dosage*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007297:Inpatients; D008297:Male; D008775:Methylprednisolone / Q000008:administration & dosage; D008875:Middle Aged; D018579:Patient Selection; D010919:Placebos; D016896:Treatment Outcome
D000893:Anti-Inflammatory Agents; D003692:Delayed-Action Preparations; D010919:Placebos; D003366:Cosyntropin; C006418:adrenocorticotropin zinc; D008775:Methylprednisolone