Inebilizumab Benefit Holds Despite Steroid Cuts: Richard Nowak, MD

Patients with myasthenia gravis (MG) in the phase 3 MINT trial weren't just measured for symptom improvement, they were also required to taper off high-dose steroids on a fixed schedule, and inebilizumab's benefit held up anyway, said Richard Nowak, MD, MS, associate professor of neurology at Yale School of Medicine and global principal investigator of the MINT trial.

A Mandatory Steroid Taper

Every enrolled patient followed the same prednisone dose reduction schedule regardless of treatment arm, reaching a dose of 5 mg per day or less by week 24, with some patients getting there earlier depending on where their dose started at enrollment. The taper wasn't incidental to the study design, it was deliberate: prednisone remains the mainstay of MG treatment, but clinicians don't want patients maintained on moderate to high doses indefinitely. With the study's randomized controlled period running 6 months for the combined population and a full year for the acetylcholine receptor (AChR) subgroup, the trial built in the same kind of monthly steroid dose reductions clinicians already use in practice, then tracked whether that taper affected disease outcomes.

"MINT was unique in that it included a protocol-specified corticosteroid taper beginning at week four after randomization," Nowak said.

Benefit Held Despite Lower Prednisone

The concern going in was real: lowering prednisone can potentially increase the likelihood of disease exacerbation and the need for rescue therapy. But the study, published in JAMA Neurology, found the opposite held for patients on inebilizumab, with reduced probability of both outcomes compared with placebo despite the mandated taper. Nowak said the drug "essentially mitigates risk of both of those occurrences" relative to placebo across both AChR and muscle-specific kinase (MuSK) antibody subtypes of generalized MG. For a field still leaning on long-term steroids as first-line therapy, he said seeing benefit on both outcomes despite an aggressive, protocol-mandated taper adds meaningfully to what's understood about inebilizumab's real-world value.

"We are observing that the probability of rescue therapy use, the probability of exacerbation is lower in the inebilizumab group despite lowering of prednisone as compared to the placebo group," Nowak said.