Use of third-line therapies in advanced sarcoidosis

Patients with advanced sarcoidosis often require third-line therapies including infliximab, adalimumab, rituximab, and repository corticotropin injection (RCI). Over time, some patients discontinue therapy.

In a retrospective review of patients at the University of Cincinnati Sarcoidosis Clinic, we identified patients who received one or more third-line treatments. Age, race, gender, organ involvement, and initial date of therapy were collected. For patients in whom a drug was discontinued, the last date of treatment, reason for drug discontinuation, and outcome of drug withdrawal were noted.

Of the 2109 patients identified, 317 (15%) had received one or more third-line therapies (infliximab: 258 patients; adalimumab: 52 patients; rituximab: 34 patients; RCI: 101 patients). Patients with neurologic, cutaneous, or ocular sarcoidosis involvement were more likely to have received third-line therapy. Overall, 225 (50.6%) of treatment regimens were discontinued. Rate of discontinuation was higher for infliximab (55%), adalimumab (58%), or RCI (43%) than for rituximab (29%, Chi square=11.959, p=0.0075). Compared to RCI, the hazard ratio (HR) for discontinuing therapy due to infection was increased for infliximab (HR=12.14, p=0.0134) and adalimumab (HR=9.71, p=0.0356). The hazard ratio was higher for drug discontinuation due to allergic reactions to infliximab (HR=9.40, p=0.0017) or adalimumab (HR=5.83, p=0.0273). For patients receiving at least two years of therapy, drug survival was significantly shorter for infliximab compared to other therapies (Chi square=5.4054, p=0.0201).

While third-line therapies are often initially effective, a significant number of patients discontinued individual treatments and initiated an alternative third-line therapy.