A recent post hoc analysis from AstraZeneca (LON:AZN) found that the monoclonal antibody anifrolumab (Saphnelo) led to consistent improvements in skin rash and arthritis in patients with systemic lupus erythematosus (SLE), which is the most common lupus type. A pooled analysis of the Phase 3 TULIP-1 and TULIP-2 clinical trials investigating anifrolumab showed the drug led to a sustained reduction in SLE symptoms based on the British Isles Lupus Assessment Group (BILAG)–based Composite Lupus Assessment (BICLA).
Anifrolumab binds to the type I interferon receptor subunit 1 and blocks all type I interferons.
If approved, anifrolumab would be a first-in-class lupus treatment. Researchers have known for decades that inflammation-causing signaling proteins known as interferons were involved in lupus. It was, however, unclear whether inhibiting interferons would provide relief to lupus patients. The TULIP clinical trial series, which draws its name from an acronym of Treatment of Uncontrolled Lupus via the Interferon Pathway, highlight the promise of targeting interferons, at least in many lupus patients.
While the TULIP trial participants with high interferon levels were among those experiencing the most significant relief from lupus symptoms, including rash and arthritis, “there were some exceptions,” said Dr. Joan Merrill, director of clinical projects, arthritis and clinical immunology program at the Oklahoma Medical Research Foundation. “If you took an endpoint that looked at partial responses rather than demanding a full response, you started to see efficacy in the low interferon people,” Merrill said. Future research could provide more clarity regarding the role of interferons in lupus patients with varying levels of the signaling proteins. “We also don’t know enough about the immune system yet,” Merrill added. Dampening the interferon signal may be good for patients, even if it isn’t apparent initially.
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Another unanswered question that will provide fodder for future research is the best strategy for targeting interferon receptors. “Is it best to completely wipe out that receptor temporarily and then let it wear off before the next dose? Or would it be better to wipe it out halfway or two-thirds of the way? Or would that be different from patient to patient?” Merrill asked.
Ultimately, several immune system functions misfire in lupus. “We have them for a reason,” Merrill said. “They’re protecting us from infections and cancers and all kinds of other important things. So, the holy grail is to learn to use these fabulous 21st-century medicines in a much more sophisticated way than we know how to do today,” she said. “The story isn’t over yet. We have a lot to learn.”