Lupus Clinical Trials May Not Be Representative of Real-World Population, Report Suggests

Patients participating in Phase 3 clinical trials testing new therapies for systemic lupus erythematosus (SLE) are not necessarily representative of real-world patient populations, according to a new report.

Even if the therapies being investigated reach the market, real-world experiences may differ significantly from trial results because many lupus patients are not eligible to participate in studies due to exclusion criteria, the report says.

The report, “RealWorld Dynamix: Systemic Lupus Erythematosus US,” was published by Spherix Global Insights, a business intelligence and market research company that specializes in the renal, autoimmune, neurologic, and rare disease markets.

Lupus is estimated to affect 1.5 million Americans, most of whom are women of child-bearing age and minorities. Currently, there it has no cure, and GSK’s Benlysta (belimumab) is the only targeted treatment approved for people with this disease (aspirin, corticosteroids such as prednisone, and hydroxychloroquine — an antimalarial — are others with FDA approval).

Lupus is a chronic disease that can manifest in a number of different organs throughout the body. Consequently, treating the disease is difficult for physicians, who often prescribe off-label medicines or a combination of therapies to help manage their patients.

A variety of potential new treatments are being investigated for lupus. But clinical trial populations must be representative of real-world patients to ensure similar effects and cost-benefit ratios after a medicine is approved.

To gain a deeper understanding of what a typical real-world lupus patient looks like — in regards to disease burden, physician touchpoints, and treatment journeys — Spherix Global Insights analyzed data from 1,032 patients, in collaboration with 201 rheumatologists in the U.S.

Most patients included in the study exhibited lupus manifestations in their joints, skin, and kidneys, despite treatment. Rheumatologists described the condition of their patients mostly as fair across several quality of life factors, such as fatigue, sleep quality, activities of daily living, work performance, social activities, and pain.

As expected, patients with manifestations of the disease across several organs had a much higher medication burden, experienced treatment changes earlier, and were thought to have an overall worse quality of life than patients who only had manifestations in a few organs.

Those who were given biologics (biologically-derived medicines) had more skin, joint, and kidney manifestations. These patients were also often treated with combination therapies, such as steroids and immunosuppressants.

Patients who received Benlysta were typically able to achieve a satisfactory response. However, while the rheumatologists estimated that only 39 percent of patients are not candidates for the therapy, most were never informed about Benlysta.

Of those who have been treated with Benlysta, most have stayed on the medication — with less than 10 percent of patients discontinuing its use, largely due to costs.

Among the off-label medications, lupus patients tended to be most frequently prescribed Rituxan (rituximab), developed by Genentech/Biogen. Most rheumatologists were satisfied with their patients’ response to the treatment. However, the lack of an indication and insurance coverage limited the use of Rituxan for many patients.

Significantly, the report emphasizes that contrary to what most of the rheumatologists believe, the majority of their patients were not appropriate candidates for most products that are in Phase 3 trials for lupus treatment, suggesting that perhaps these therapies are not useful in the real world.

For example, Janssen is currently recruiting up to 500 patients for a Phase 3 trial (NCT03517722) of Stelara (ustekinumab). However, less than a third of the patients analyzed would be eligible for recruitment because of exclusion criteria that includes those who have previously used biologics, have experienced more severe flares, or have severe or unstable manifestations.

The significant proportion of patients who are ineligible for participation in these trials suggests that even if these therapies are approved, the “post-marketing experience may be very different from clinical trial results,” according to the press release from Spherix Global Insights.

The report draws attention to a discrepancy that exists between current clinical trial populations and the proportion of real-world patients who will actually be able to use the medications being investigated. According to Spherix, the report can be used by pharmaceutical developers to gain insight into how treatments are currently being utilized and identify where future opportunities may lie.