Recent advances in the biologic therapy of lupus: the 10 most important areas to look for common pitfalls in clinical trials

ABSTRACT

Introduction: Systemic lupus erythematosus (SLE) is an autoimmune disease affecting different organs. The improved knowledge of the disease’s pathogenesis has contributed to the emergence of immune targets and new biologic drugs directed at them. Although rheumatologists continue to use off-label biologics in SLE resistant to other immunosuppressants, only belimumab has been approved as a biological therapy since 2011.

Areas covered: In this review, an overview is provided on: 1) the classification of the biologic drugs in clinical trials and of those under research; 2) the results of clinical trials of biologic therapy with an interpretation of pitfalls and syntheses of potential approaches to overcome these pitfalls and, 3) the commonly used disease activity metrics and composite indices for assessing response to drugs.

Expert opinion: Some drugs that have failed in previous drug trials have shown to be efficacious in the treatment of lupus in observational studies. Moreover, the post-hoc analyses of the data of negative drug trials have shown that results of the same trials could be altered with the modification of some pitfalls. For future clinical trials, the consideration of these pitfalls is crucial when designing clinical trials. This could potentially enhance the approval of novel drugs for SLE.

KEYWORDS:

• Systemic lupus erythematosus
• biological therapy
• clinical trials
• immunosuppressive agents

Article highlights

• The B-cells directed biological therapies are the group of biologic drugs most commonly used for SLE resistant to standard of care treatment.

• Belimumab is the only biologic drug approved for SLE, and it has been the only new drug approved for the disease since 1959.

• Currently there are ongoing promising clinical trials on agents targeting B cells, T cells, and humoral mediators (including cytokines and interferons) for the treatment of SLE

• Lupus trials have taught us important lessons and common areas to look for pitfalls need to be accounted for by lupologists and trialists to ensure the success of our future trials.

• Targeted therapies for trials focusing on renal, extra-renal or more specifically organ-specific manifestations may lead to the approval of new drugs.

This box summarizes key points contained in the article.

Declaration of interest

Z Touma has consulted for GlaxoSmithKline, Merck Serono and Janssen Pharmaceuticals. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Additional information

Funding

This work was supported by the University of Toronto Lupus Research Program which is funded by the University Health Network and the Toronto General & Western Hospital Foundation. J Medina-Rosas is supported by the Lupus Ontario Geoff Carr Lupus Fellowship while H Al-Rayes is supported by the Saudi Cultural Bureau. Z Touma holds a Young Investigator Salary Award provided by The Arthritis Society. The University of Toronto Lupus Clinic is supported by the University Health Network, Lupus Foundation of Ontario and the Lou Rocca Family.