Use of third-line therapies in advanced sarcoidosis.

OBJECTIVES: Patients with advanced sarcoidosis often require third-line therapies including infliximab, adalimumab, rituximab, and repository corticotropin injection (RCI). Over time, some patients discontinue therapy. METHODS: 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. RESULTS: 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). CONCLUSIONS: While third-line therapies are often initially effective, a significant number of patients discontinued individual treatments and initiated an alternative third-line therapy.

Presence of onconeural antibodies in sarcoidosis patients with parasarcoidosis syndrome.

BACKGROUND: Bothersome symptoms from sarcoidosis can develop in the absence of identified granulomas. These parasarcoidosis complaints can include small fiber neuropathy, diaphoresis, dysautonomia, and fatigue. Similar issues are also encountered in some cancer patients, especially those with onconeural antibodies. METHODS: Serum was obtained for onconeural antibody testing from sarcoidosis patients with parasarcoidosis symptoms seen at the University of Cincinnati Sarcoidosis clinic during a six month period. Detection of antibodies was performed using an onconeural antibody panel. RESULTS: A total of 268 patients with sarcoidosis and one or more features suggesting parasarcoidosis symptoms were enrolled in the study. Of these, 60 (22.4%) had one or more positive onconeural antibodies. In a control group of 46 non sarcoidosis patients seen in the interstitial lung disease clinic, there were only three patients with a positive antibody (Chi square=6.143, p=0.0132). A subgroup of sarcoidosis and control patients completed the small fiber neuropathy screening list. Sarcoidosis patients had a significantly higher score than the control patients (sarcoidosis: 7 [0-49] (Median [range] versus non sarcoidosis: 3 [0-31], p=0.0074). However, no significant differences were measured in the SFNL scores for sarcoidosis patients with an onconeural antibody (9 [3-36]) versus without (7 [0-49]). CONCLUSION: In patients with parasarcoidosis symptoms, approximately 30% have evidence of onconeural antibody production. This may be a potential cause for parasarcoidosis symptoms in some patients.