How Trial Lupus Drug Stelara May Work to Reduce Flares
Following the successful Phase 2 trial of experimental lupus drug Stelara® (ustekinumab), researchers returned to the study data to uncover just how the treatment works.
As previously reported, Phase 2 results indicated the drug is effective in managing lupus activity and reducing flares at one-year. Of the 60 participants with active lupus who received the trial drug Stelara, 62% demonstrated significant overall improvement in disease activity, compared to just 33% of those in the placebo group. People in the treatment group who showed signs of disease activity improvement were classified as “responders” and those who did not improve on the drug were considered “non-responders.”
To learn more about how and why the drug worked, the researchers assessed blood samples collected from the participants at baseline and then later at follow-up visits after Stelara administration. As expected, the drug effectively led to increased levels of its treatment target, p40, a specific subunit shared by two different proteins implicated in lupus disease activity. However, both the responders and non-responders showed similar increases in p40, despite experiencing different outcomes on the treatment.
Instead, the difference appears to be in responder and non-responder levels of interferon type II IFN, a type of protein produced in the inflammatory response to infection. Blood levels of type II IFN decreased significantly in the responder group, but not in the non-responders, even though both groups had similar levels of type II IFN at baseline. These findings suggest that type II IFN in Stelara responders may be dependent on p40 signaling, while other factors independent of p40 may perpetuate type II IFN in non-responders. The study also indicates the important role Stelara likely plays in blocking interleukin-12 activity, which promotes type II IFN production.
Although the Phase 3 trial for Stelara was discontinued due to its lack of effectiveness as a lupus treatment, the scientific community is learning from the trial data, which can help inform further lupus research moving forward. Continue to follow the Lupus Foundation of America for updates on Stelara. Learn more about treatments being studied for lupus.