JAK inhibitors, ustekinumab show promise in SLE, more data needed
DESTIN, Fla. — JAK inhibitors and ustekinumab have emerged as promising treatments for systemic lupus erythematosus, and more research is required to help patients who continue to report a low quality of life despite recent advancements, according Ronald F. van Vollenhoven, MD, PhD, of the Amsterdam University Medical Center.
“According to an SLE patient survey in Sweden, taken in 2011, the average EQ-5D score measuring quality of life was comparable to those with advanced COPD, to treated stage 3 or 4 Hodgkin’s lymphoma or to patients with advanced HIV disease,” van Vollenhoven told attendees at the 2019 Congress of Clinical Rheumatology. “This is a poor result for patients with lupus, and it’s especially disappointing because Sweden has a lot of things going for it — it has a national health care system, there a lot of rheumatologists and the approved medications are all available.”
“These patients ought to be doing better, and yet, despite all of these circumstances, the quality of life is still disappointing and shows we have to get better at treating lupus,” he added.
There is currently one biologic approved for SLE — belimumab (Benlysta, GlaxoSmithKline) — which has been shown to be effective, with a modest steroid-sparing effect, particularly in patients with high disease activity. However, according to van Vollenhoven, several other biologics based on the same mechanism have failed in phase 2 and 3 clinical trials. In addition, although many experts believe rituximab (Rituxan, Genentech) can be useful in severe refractory patients with SLE, it has nonetheless failed in two trials, he said.
Anifrolumab, an interferon receptor antagonist, demonstrated promising results in a 2015 phase 2 trial. However, AstraZeneca, the drug’s developer, released a press release in 2018 revealing that it nonetheless failed its primary endpoint in one phase 3 TULIP 1 trial.
“The lupus community is really holding its breath to hear what exactly happened in the TULIP 1 trial,” van Vollenhoven said. “Was it a total failure? Did it just miss? Is there a regulatory way forward? The interferon receptor antagonist was very exciting, and it fit a lot of what we know about lupus. But then there was the disappointing press release, where we still don’t know what the whole story its.”
Meanwhile, JAK inhibitors, specifically baricitinib (Olumiant, Eli Lilly), and the IL-12 and IL-23 inhibitor ustekinumab (Stelara, Janssen) have recently emerged as promising avenues for treatment in SLE, van Vollenhoven said.
In a phase 2 trial published in The Lancet in 2018, the 4-mg dose of baricitinib significantly improved the signs and symptoms of active SLE in patients who had not responded adequately to standard of care. According to van Vollenhoven, the drug is currently in a phase 3 trial.
In another phase 2 trial, conducted by van Vollenhoven and colleagues and presented at the 2018 American College of Rheumatology Annual Meeting, ustekinumab provided sustained clinical benefit in global and organ-specific SLE activity measures through 1 year. Its safety profile was consistent with other known indications for the drug.
“For lupus trials, it was almost sensational,” van Vollenhoven said. “However, it was a phase 2 trial, a smaller trial, with about 100 patients, and it is important to remember that drugs that seem encouraging in phase 2 may not be so good.”
Still, van Vollenhoven added that he remains optimistic that additional research will provide rheumatologists and their patients with additional breakthroughs and treatments for SLE.
“I think that we have come quite far in lupus but not quite far enough,” van Vollenhoven said. “There is a lot of excitement in the lupus community about these developments while we wait for what is going to happen. However, for now, we still have to do our best to treat our patients with the medications that are available. Still, I think there will be more coming soon.” – by Jason Laday
van Vollenhoven R. Targets for biologics in SLE. Presented at: Congress of Clinical Rheumatology; May 2-5, 2019; Destin, Fla.
Disclosure: van Vollenhoven reports research grants from AbbVie, BMS, GlaxoSmithKline, Pfizer and UCB; consulting fees from AbbVie, AstraZeneca, Biogen, Biotest, Bristol-Myers Squibb, Celgene, Gilead, GlaxoSmithKline, Janssen, Eli Lilly, Novartis, Pfizer, Servier and UCB; and speaking fees from AbbVie, Eli Lilly and UCB.