Biologic discontinuation studies: a systematic review of methods.

OBJECTIVES

We conducted a systematic review to assess the design and 'failure definition' in studies of biologic discontinuation in rheumatoid arthritis (RA).

METHODS

We found 403 studies on PubMed, and included nine published papers and five abstracts from scientific meetings. We used a structured extraction form to collect information regarding study design and outcome (failure) definition.

RESULTS

Three types of studies were found: randomised controlled trials, long-term extension studies of clinical trials and prospective discontinuation studies. The largest study had 196 subjects in the discontinuation arm. Most studies allowed concomitant use of non-biologic drugs at biologic discontinuation. Heterogeneity was also found in the failure definition. Although all studies used measures of disease activity, the threshold for failure and the time point of assessment differed among studies. Few studies incorporated changing use of non-biologic drugs or glucocorticoids into the failure definition.

CONCLUSIONS

Although many studies have examined the outcome of biologic discontinuation, they have all been relatively small. Typical practice studies from registries may add important information but will likely need to rely on a broader failure definition.