This success has naturally prompted new questions about the role of IL-12 and IL-23 in the pathophysiology of lupus, and these questions have yielded new insights. “The scientific community knows a tremendous amount about lupus disease mechanisms,” Dr. Crow says. “There are many candidate therapeutic targets and promising agents ready for testing.”
Trial Design
The future of lupus research will also see rheumatologists address current problems in lupus clinical trial design. These problems largely stem from the fact that many lupus patients can, to some extent, successfully manage their SLE with the currently available broad immunosuppressive drugs. As a result, drug trials must often be performed with patients taking background immunosuppression.
However, the alternative can also complicate clinical trials. This complication occurs when patients are weaned off their immunosuppressants, but the weaning process for steroids may affect the immune system in ways not fully understood and leave patients with new or unstable symptoms. Thus, researchers continue to wrestle with the question of how steroids should be handled in the context of a clinical trial.
To make matters worse, explains Dr. Crow, the current outcome measures for lupus are not sufficiently informative for clinical trials. Example: Arthritis can be difficult to assess in lupus. Moreover, patients with lupus often experience pain that is difficult to clearly score, making improvements in pain symptoms hard to quantify.
Lastly, targeted drugs may require careful patient selection that identifies patients most likely to respond to the drug. Unfortunately, it may not be possible to identify these patients in advance of a clinical trial. Instead, post-hoc analysis may be necessary to determine the patients most likely to benefit from a given targeted therapy.
As investigators from the NIH, universities, pharmaceutical companies and computer science specialists come together, their work will continue to reveal new drug targets and approaches to documenting drug efficacy. These efforts are accelerating the development of new treatments and revealing a bright future for patients with lupus.
Lara C. Pullen, PhD, is a medical writer based in the Chicago area.
References
- Pullen LC. AMP RA/Lupus Network shares its progress. The Rheumatologist. 2017 Sep:11(9).
- AC Grammer, MM Ryals, SE Heuer, et al. Drug repositioning in SLE: Crowd-sourcing, literature-mining and big data analysis. Lupus. 2016 Sep;25(10):1150–1170.
- RF van Vollenhoven, BH Hahn, GC Tsokos, et al. Efficacy and safety of ustekinumab, an IL-12 and IL-23 inhibitor, in patients with active systemic lupus erythematosus: Results of a multicentre, double-blind, phase 2, randomized, controlled study. Lancet. 2018 Oct 13;392(10155):1330–1339.
Revised Oct. 3, 2019, to correct Dr. Lipsky’s title.
