Expert Study Finds Lupus Clinical Trials Poorly Reflect Real-Life Situations

Treatment of systemic lupus erythematosus (SLE) needs to reflect the involvement of particular organs as well as the severity of disease, according to a study presented at the Congress of Clinical Rheumatology Annual Meeting, scrutinizing published clinical trials of lupus. The study advocated giving more weight to clinical experience than treatment algorithms — built on insufficient clinical trial data — when choosing the appropriate treatment.

The investigation, “Lupus management after failure of first-line treatment,” presented by Janet Pope of the University of Western Ontario Schulich School of Medicine in Canada, employed a group of SLE experts, who performed a literature review of randomized clinical trials.

“We wanted to achieve consensus on treatment by having each participant offer their opinion, assuming there was disease activity due to SLE, current flare with only one organ system, access to appropriate medications, and full doses tolerated sufficiently before altering treatment,” said Pope, a professor of medicine, epidemiology, and biostatistics.

The lupus experts together developed and improved treatment guidelines, and once a final treatment diagram was agreed upon, they were asked to state how much they agreed with the final solution. In this way the most common order of treatment choices were selected.

The study showed that experts generally agreed that pulmonary hypertension should be ruled out or confirmed with appropriate techniques, that general infections need to be ruled out, and that the presence of kidney disease should be confirmed by a kidney biopsy.

In terms of treatment, they also agreed that hydroxychloroquine is a crucial drug that should constitute a cornerstone of therapy.

At the meeting, which was May 12-15 in Destin, Florida, Pope stated that trials are not accurately representing patient populations, and fail to take into account real-life scenarios where patients are typically treated with multiple drugs.

“Also, while many current drugs are effective, there is a sense that type II errors have occurred, where a specific drug could work but is not shown to be positive,” she said, suggesting that theories of a drug’s inefficiency were supported in trials, when in fact, the theory was wrong.

Pope also said that future clinical trials should have realistic expectations of outcomes where improvement can be measured in various ways. “Efficacy compared to placebo may not be the primary goal. Instead, steroid-sparing effect of the drug, better safety, or favorable time to clinical worsening may be the goal,” she said.