Consequences of delayed therapy with second-line agents in rheumatoid arthritis: A 3 year followup on the hydroxychloroquine in early rheumatoid arthritis (HERA) study

Objective, To assess the longterm effect of delaying therapy with second-li ne agents in patients with early rheumatoid arthritis (RA). Methods, One hundred nineteen patients who participated in a 9 month placeb o controlled randomized trial of hydroxychloroquine sulfate (HCQ) were foll owed prospectively for an additional 3 years. Those randomized to HCQ are r eferred to as the early treatment group and those randomized to placebo as the delayed treatment group. Participants were assessed annually for pain [ Arthritis Impact Measurement Scales (AIMS) and Stanford Health Assessment Q uestionnaire (HAQ)], physical disability (AIMS and HAQ), and the RA global well being scale (AIMS). Conversion of results into standard deviation (SD) units permitted defining a substantial difference as per Felson as > 0.30 SD units and a clinically indistinguishable difference as less than or equa l to 0.06 SD units. Results, One hundred fifteen patients (97%) participated and complete data were available on 104 (87%). Compared to the early treatment group, the del ayed group remained worse for both the pain and the physical disability out comes over the additional 3 year followup, The difference in the RA global well being score became clinically indistinguishable for the early and dela yed groups only after the 2 year post-trial assessment. The between-group d ifferences were not explained by post-trial therapy with corticosteroids, o ther second-line agents, or nonsteroidal antiinflammatory drugs and analges ic preparations. Conclusion. These findings show that a delay in instituting therapy with se cond-line agents, even a 9 month delay in instituting a moderately powerful second-line agent such as HCQ, has significant effects on longterm patient outcome, and provides strong evidence in support of early therapy in RA.