However, Dr. Merrill and her coauthors noted that “ILLUMINATE-1 stipulated that new, increased or decreased standard of care medications would define a patient as nonresponsive, whereas only new or increased medications in [ILLUMINATE-2] determined nonresponse.” Analyses that did not consider patients who decreased antimalarials or immunosuppressants to be nonresponders found a significantly higher SRI-5 response rate for patients who took tabalumab every 4 weeks (37% vs. 29.8% with placebo), but not for biweekly dosing (34.1%).
In an interview, Dr. Merrill put forward the idea that rethinking study design for SLE drugs might make sense. Going forward, she said, investigators should consider breaking the population into two subgroups. For the sicker patients, background medication would have to be maintained, but the data would be more interpretable if this subgroup were analyzed separately. Patients who are less ill, she said, could be moved to homogeneous background drugs, easing data analysis and minimizing the effect of complicated and largely unknown biochemical interactions.
Regarding the rare events of depression and suicidal ideation seen in the treatment arms but not the control arm of the study, Dr. Merrill said, “You can never rule out a biochemical cause, even for a rare finding, and suicidal ideation and depression are serious events which were also numerically greater in the phase III trials of ... belimumab, but also quite rare in those studies, too.” She said that she would be interested in tracking the clinical course of those patients who became depressed and learning more about immune signaling in those individuals. “There is a lot to be learned about these treatments,” she said.
Eli Lilly and Company, tabalumab’s manufacturer, elected not to proceed with the drug development and approval process. Noting that more therapies are needed for SLE, Dr. Merrill said, “I’m very sad that Lilly decided not to develop this drug further. I understand it, but as a doctor, I’m still very sad.”
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