Table 3

Potential explanations for the apparent discrepancy in clinical response reported in clinical experience and DBRCTs

Clinical experience

Randomised controlled trials

Disease activity

Refractory to conventional immunosuppressants

Rituximab was used as an add-on therapy to background immunosuppressants

Favourable response reported in life-threatening cases, often including a range of organ-system involvement such as CNS manifestations, cytopenias and others

Life-threatening cases and those with CNS manifestations were not evaluated in controlled trials. This setting warrants a dedicated study

Clinical response

No defined pretreatment, therefore complete and partial

responders might not be clearly distinguished

Predefined endpoints were stringent, perhaps driven by the impressive responses seen in clinical experience in an uncontrolled setting

Improvement in one system alone might qualify for response, regardless of a flare or lack of response in another organ system

Predefined and usually stringent. For example, despite clinical response and steroid-sparing effect, a reduction in proteinuria that does not meet the predefined threshold would not qualify as complete/partial response

Background immunosuppressants

Flexibility in changes to background immunosuppressants including the dose of corticosteroids

Changes to or deviation with predefined background therapy would qualify as nonresponder

Concomitant use of large dose of steroids is uncommon

Concomitant use of large dose of corticosteroids might have limited any beneficial effects of rituximab, the extent of which may be more restricted in such a setting than previously assumed

Rituximab dosing-regimen

Variable between reports

Predefined dosing regimen

Steroid tapering

Steroid-sparing effect is not a requirement to define response and therefore favourable response might be overestimated

Steroid dosing effect was included in the definition of clinical response

Adverse events

No standardised reporting of adverse events. Therefore, the true incidence of serious adverse events in clinical practice is not comparable with that reported in other uncontrolled studies or controlled clinical trials

Rituximab therapy appears to be safe as no there were no significant differences in serious adverse events when compared with standard-of-care treatment

Follow-up period

Not defined, therefore it is not known how many responders had sustained response in the long term

Predefined, therefore, unless long-term studies are undertaken, it would be difficult to detect the importance of effects seen at relatively short-term follow-up

CNS, central nervous system.

Reddy et al. Arthritis Research & Therapy 2013 15(Suppl 1):S2   doi:10.1186/ar3910