Prediction of relapse after discontinuation of infliximab therapy in severe sarcoidosis

Abstract

Infliximab is effective as a third-line therapeutic for severe sarcoidosis; however, long-term efficacy is unknown. The aim of this study was to assess the relapse rate after discontinuation of infliximab in sarcoidosis patients and predict relapse by analysis of the activity marker soluble interleukin (IL)-2 receptor (sIL-2R) and maximum standardised uptake value (SUVmax) of 18 F-fluorodeoxyglucose positron emission tomography (FDG PET).In this retrospective cohort study, the proportion of relapse was analysed using the Kaplan-Meier method and predicting factors were studied using Cox regression.47 sarcoidosis patients who started infliximab therapy were included in the risk analysis. Kaplan-Meier analysis revealed a median time to relapse of 11.1 months and showed that 25% of the cohort relapsed within 4 months. Both mediastinal SUVmax o6.0 on FDG PET (hazard ratio 3.77, p,0.001) and serum sIL-2R o4000 pg?mL -1 (hazard ratio 2.24, p50.033) at start of therapy predicted relapse. In multivariate analysis, a mediastinal SUVmax o6.0 at initiation of therapy was an independent predictor of relapse (hazard ratio 4.33, p,0.001).The majority of patients that discontinued infliximab therapy relapsed. High serum sIL-2R and high SUVmax on FDG PET at initiation of therapy were significant predictors of relapse. These results suggest close monitoring of patients in this category when they discontinue infliximab treatment. @ERSpublications Two significant predictors of relapse after discontinuation of infliximab therapy for severe sarcoidosis

Discrepant elevation of sIL-2R levels in sarcoidosis patients with renal insufficiency

“…sIL-2R was previously shown to correlate with the amount of CD4 + T-lymphocytes in bronchoalveolar lavage fluid [3]. Furthermore, it was shown that sIL-2R >4000 pg·mL −1 was a significant predictor of relapse after discontinuation of infliximab therapy and that sIL-2R is a suitable prognostic marker for disease progression [4,5]. We observed, however, that in a small number of patients with co-existing renal insufficiency, sIL-2R can be disproportionately high without marked signs of disease activity based on 18 F-fluorodeoxyglucose positron emission tomography (FDG-PET), ACE and the clinical presentation.…”

Effectiveness of infliximab in refractory FDG PET-positive sarcoidosis

“…Patients with high activity on 18 F-fluorodeoxyglucose (FDG) by positron emission tomography (PET) were often shown to relapse after infliximab therapy was discontinued [23], possibly suggesting a good initial response in those patients.…”

Association of the TNF- G-308A polymorphism with TNF-inhibitor response in sarcoidosis

“…In case of intolerable side-effects or steroid resistance, second-line treatment options should be considered, such as methotrexate (MTX), azathioprine or leflunomide, but these therapies may also be subject to failure or intolerance [8][9][10]. Another option to consider is TNF inhibitors, which inhibit the potent pro-inflammatory TNF-a, often a predominant problem in patients with refractory sarcoidosis, and these have shown promising results [11][12][13][14]. However, a drawback of TNF inhibitors is considerable treatment costs [15].…”