Despite a positive phase 3 result, longer, more detailed studies are required, according to one expert.
Inebilizumab, an IgG1 monoclonal antibody, safely reduces IgG4-related disease flares, according to new data from an international clinical trial.
Inebilizumab received FDA approval earlier this month based on the results of the study, making it the first and only such approved treatment for IgG4-related disease.
Patients with IgG4-related disease have few treatment options available to them, none of which have quality data to support their long-term use and safety. B cell targeting therapies, such as inebilizumab, certainly fall into this description.
As part of a recent phase 3 trial, published in NEJM, 135 patients with IgG4-related disease (88 men, mean age 52 years) received three infusions of inebilizumab or placebo – the first on day one of the trial, the second on day 15, and the third at 26 weeks. Any patients taking glucocorticoids had their doses reduced by 5mg/day each fortnight from week eight onwards until discontinuation. All patients were followed up 12 months after starting the trial.
Patients receiving inebilizumab were 87% less likely to have and require treatment for an IgG-4-related disease flare than patients treated with placebo (hazard ratio 0.13, 95% confidence interval 0.06-0.28). Only 10% of patients in the inebilizumab group experienced a disease flare, compared to 60% of patients in the placebo group.
There was also an effect on the time to disease flare, with patients in the placebo group having a median of 246 days before flare. The median time to event could not be calculated in patients receiving inebilizumab due to the small number of flare-related events in this group.
Inebilizumab led to a five-fold increase in the odds of patients experiencing a flare-free, glucocorticoid-free remission relative to placebo.
“Although the glucocorticoid taper in both groups was appropriate to ensure that participants in the placebo group received treatment that was aligned with standard care, the trial results suggest the potential for the use of inebilizumab as a standalone therapy for remission maintenance in IgG4-related disease,” the researchers noted.
Almost all patients experienced at least one adverse event (97% in the inebilizumab group compared to 98% in the placebo group), although the proportion of patients experiencing serious adverse events (18% versus 9%) and infusion-related reactions (4% versus 7%) were far lower.
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Professor Robert Spiera, a rheumatologist at Weill Cornell Medical College in the US, provided a balanced reflection on the new research.
“This is one of the largest and most carefully conducted prospective clinical trials of a therapeutic intervention in IgG4-related disease, and it clearly showed the benefit of the anti-CD19 strategy,” he wrote in his accompanying editorial.
“These results show the efficacy of inebilizumab in IgG4-related disease. [However,] the clinical importance of that benefit seems intuitive but has not really been captured in this clinical trial.
“No specific benefit regarding accrual of organ damage or advantages in terms of patient-reported outcomes were captured. Moreover, the long-term safety of inebilizumab, particularly with repeated doses used as a remission-maintenance strategy, could not be determined in a 52-week trial.”
Professor Spiera highlighted a three-year open-label follow-up study that is currently underway, which could potentially provide clearer answers regarding the safety of inebilizumab, but also felt comparing its efficacy with other immunosuppressive therapies should be considered.
