Clinical trials for lupus have a high failure rate with only two drugs approved for the treatment of general systemic lupus erythematosus (SLE) in the last 60 years, despite at least twenty late-stage clinical trial programmes being pursued. Reasons for the high failure rate, especially in phase 3 trials, potentially include issues with the product being tested, but also issues intrinsic to the disease area. One domain is biological heterogeneity, which will never be directly under our control, although it might one day be addressed in a personalised medicine approach. The other, while also complex, is directly under our control: how trials are designed.
Analysis of recent trial success rates suggests some common factors among successful trials, including the use of glucocorticoid tapering. However, other data point to issues relating to the outcome measures used;1 the SLE responder index (SRI) and BILAG-based composite lupus assessment (BICLA) endpoints are each based on 30-year-old disease activity measures that were never designed for use in clinical trials. A global academia-industry-patient collaboration has now commenced a project to reinvent clinical outcome assessment for use as a treatment response measure in SLE clinical trials: treatment response measure for SLE (TRM-SLE).2 A five-stage scientific protocol using Delphi and nominal consensus methods has been developed to lead to this novel outcome measure, which will subsequently be validated in clinical trial data both retrospectively and prospectively.
Connelly K, et al. Clinician-reported outcome measures in lupus trials: a problem worth solving. Lancet Rheumatol. 2021. doi:10.1016/s2665-9913(21)00119-3.
Connelly K, et al. Towards a novel clinical outcome assessment for systemic lupus erythematosus: first outcomes of an international taskforce. Nat Rev Rheumatol. 2023 Jul 11. doi: 10.1038/s41584-023-00993-7. Epub ahead of print.
Increased understanding of the reasons for the lack of success of late-stage clinical trials in SLE
Increased understanding of the limitations of current trial measures
Awareness of a global project to develop and validate a new SLE clinical trial measure, TRM-SLE
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