Infectious Risk Stratification in Multiple Sclerosis Patients Receiving Immunotherapy - An Update

Objective: To investigate the prevalence of infections in two independent German patient cohorts with MS/NMOSD. Background: The increasing number of potent treatments for MS warrants screening for infections. Design/Methods: Retrospective chart review study of MS/NMOSD patients who underwent testing for infections between 2014 and 2016. Furthermore, we provide an update on the latent tuberculosis infection (LTBI) prevalence in Dusseldorf by analyzing all interferon-γ-release assays (IGRA) performed between January 2017 and October 2018. Results: 6 out of 80 tested patients (Dusseldorf cohort) and 2 out of 97 tested patients (Munster cohort) had a LTBI between 2014 and 2016; total 3.95%, 95% CI 2–8%. Active tuberculosis was ruled out by routine blood work-up, chest X-ray, microbiological testing of sputum and urine. Highly active immunomodulatory therapy in parallel to antibiotic LTBI treatment did not lead to a tuberculosis reactivation. The side effect profile of tuberculosis therapeutics in our patients as well as strategies to deal with these are presented. Testing for HIV, hepatitis B/C, Varicella zoster virus and Treponema pallidum revealed no unexpected results. Between January 2017 and October 2018, 12 out of 283 tested patients in Dusseldorf had a LTBI; total 4.24%, 95% CI 2.3–7.4%. In 15 out of 283 tested patients, the first IGRA was not evaluable due to negative positive controls; total 5.3%, 95% CI 3.2–8.7%. Retesting revealed negative results in 7 patients, but tests of 8 patients remained unevaluable. 3 out of 8 patients received fingolimod, 2 alemtuzumab, 1 pegylated interferon beta-1a, 1 dimethyl fumarate and 1 no therapy. Conclusions: LTBI is frequent (>1%). Screening should be performed before embarking on immunomodulatory therapies to allow treatment and mitigation of the risk of a reactivation. In our cohort, immunomodulatory therapy 1.) in parallel to LTBI treatment did not lead to a reactivation and 2.) may influence the results of serological testing. Disclosure: Dr. Graf has nothing to disclose. Dr. Leussink has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen and Novartis Pharmaceuticals. Dr. Leussink holds stock and/or stock options in Biogen. Dr. Leussink has received research support from Biogen and Novartis Pharmaceuticals. Dr. Dehmel has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Novartis. Dr. Ringelstein has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Novartis, Bayer Vital GmbH, Ipsen, Bayer Schering, Biogen Idec, Merz, Genzyme, Teva and Merck. Dr. Goebels has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Roche. Dr. Goebels has received research support from Novartis, and Roche. Dr. Adams has nothing to disclose. Dr. MacKenzie has nothing to disclose. Dr. Warnke has nothing to disclose. Dr. Feldt has nothing to disclose. Dr. Lammerskitten has nothing to disclose. Dr. Klotz has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Sanofi Genzyme, Novartis Pharmaceuticals, Merck Serono, and Biogen. Dr. Klotz has received research support from Novartis Pharmaceuticals and Biogen. Dr. Meuth has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Almirall, Amicus Therapeutics Germany, Bayer, Biogen, Celgene, Chugai Pharma, Diamed, Genzyme, MedDay Pharmaceuticals, Merck Serono, Novartis, Novo Nordisk, ONO Pharma, QuintilesIMS, Roche, Sanofi-Aventis, and Teva. Dr. Meuth has received research support from Almirall, Amicus Therapeutics Germany, Bayer, Biogen, Celgene, Chugai Pharma, Diamed, Genzyme, MedDay Pharmaceuticals, Merck Serono, Novartis, Novo Nordisk, ONO Pharma, QuintilesIMS, Roche, Sanofi-Aventis, and Teva. Dr. Wiendl has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Abbvie, Actelion, Alexion, Biogen, Cognomed, Evgen, F. Hoffmann-La Roche Ltd, MedDay Pharmaceuticals, Merck Serono, Novartis, Roche Pharma AG, Sanofi-Genzyme, and TEVA. Dr. Wiendl has received research support from Biogen, GlaxoSmithKline GmbH, Roche Pharma AG, and Sanofi-Genzyme. Dr. Hartung has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Bayer Healthcare, Biogen, Geneuro, Genzyme, Medimmune, Merck, Receptos Celgene, Novartis, Roche, CSL Behring. Dr. Aktas has nothing to disclose. Dr. Albrecht has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Roche, Merck, Bayer-Healthcare, Allergan, Biogen, IPSEN, Merz, Novartis, TEVA. Dr. Albrecht has received research support from Biogen, Ipsen, Novartis and Roche.