PMID- 33598901 OWN - NLM STAT- MEDLINE DCOM- 20210421 LR - 20220422 IS - 1438-8790 (Electronic) IS - 0934-8387 (Linking) VI - 75 IP - 4 DP - 2021 Apr TI - Joint Statement (DZK, DGRh, DDG) on the Tuberculosis Risk with Treatment Using Novel Non-TNF-Alpha Biologicals. PG - 293-303 LID - 10.1055/a-1294-1580 [doi] AB - BACKGROUND: While the risk of tuberculosis (TB) reactivation is adequately documented in relation to TNF-alpha inhibitors (TNFi), the question of what the tuberculosis risk is for newer, non-TNF biologics (non-TNFi) has not been thoroughly addressed. METHODS: We conducted a systematic review of randomized phase 2 and phase 3 studies, and long-term extensions of same, published through March 2019. Of interest was information pertaining to screening and treating of latent tuberculosis (LTBI) in association with the use of 12 particular non-TNFi. Only rituximab was excluded. We searched MEDLINE and the ClinicalTrial.gov database for any and all candidate studies meeting these criteria. RESULTS: 677 citations were retrieved; 127 studies comprising a total of 34,293 patients who received non-TNFi were eligible for evaluation. Only 80 out of the 127 studies, or 63 %, captured active TB (or at least opportunistic diseases) as potential outcomes and 25 TB cases were reported. More than two thirds of publications (86/127, 68 %) mentioned LTBI screening prior to inclusion of study participants in the respective trial, whereas in only 4 studies LTBI screening was explicitly considered redundant. In 21 studies, patients with LTBI were generally excluded from the trials and in 42 out of the 127 trials, or 33 %, latently infected patients were reported to receive preventive therapy (PT) at least 3 weeks prior to non-TNFi treatment. CONCLUSIONS: The lack of information in many non-TNFi studies on the number of patients with LTBI who were either excluded prior to participating or had been offered PT hampers assessment of the actual TB risk when applying the novel biologics. Therefore, in case of insufficient information about drugs or drug classes, the existing recommendations of the German Central Committee against Tuberculosis should be applied in the same way as is done prior to administering TNFi. Well designed, long-term "real world" register studies on TB progression risk in relation to individual substances for IGRA-positive cases without prior or concomitant PT may help to reduce selection bias and to achieve valid conclusions in the future. CI - Thieme. All rights reserved. FAU - Diel, R AU - Diel R AD - Institute for Epidemiology, University Medical Hospital Schleswig-Holstein, Campus Kiel, Germany. Member of the German Center for Lung Research (ARCN). AD - LungClinic Grosshansdorf, Germany. Airway Research Center North (ARCN), German Center for Lung Research (DZL). AD - German Central Committee against Tuberculosis, Berlin, Germany. FAU - Schaberg, T AU - Schaberg T AD - German Central Committee against Tuberculosis, Berlin, Germany. FAU - Nienhaus, A AU - Nienhaus A AD - Institution for Statutory Accident Insurance and Prevention in the Health and Welfare Services (BGW), Hamburg, Germany. AD - Institute for Health Service Research in Dermatology and Nursing, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. FAU - Otto-Knapp, R AU - Otto-Knapp R AD - German Central Committee against Tuberculosis, Berlin, Germany. FAU - Kneitz, C AU - Kneitz C AD - Medicine, Rheumatology, rheumatological main practice Schwerin, Germany. FAU - Krause, A AU - Krause A AD - Department of Rheumatology, Clinical Immunology and Osteology, Immanuel Hospital Berlin, Germany. FAU - Fabri, M AU - Fabri M AD - Department of Dermatology, University of Cologne, Germany. FAU - Mrowietz, U AU - Mrowietz U AD - Psoriasis Center, Department of Dermatology, University Medical Center Schleswig-Holstein, Campus Kiel, Germany. FAU - Bauer, T AU - Bauer T AD - German Central Committee against Tuberculosis, Berlin, Germany. FAU - Hacker, B AU - Hacker B AD - German Central Committee against Tuberculosis, Berlin, Germany. LA - eng PT - Journal Article PT - Systematic Review TT - Gemeinsame Stellungnahme des Deutschen Zentralkomitees zur Bekampfung der Tuberkulose (DZK), der Deutschen Gesellschaft fur Rheumatologie (DGRh) und der Deutschen Dermatologischen Gesellschaft (DDG) zum Tuberkuloserisiko unter Therapie mit neuen Biologika (Non-TNF-alpha-Inhibitoren). DEP - 20210217 PL - Germany TA - Pneumologie JT - Pneumologie (Stuttgart, Germany) JID - 8906641 RN - 0 (Biological Products) RN - 0 (Tumor Necrosis Factor-alpha) SB - IM MH - *Biological Products/adverse effects MH - Clinical Trials, Phase II as Topic MH - Humans MH - *Latent Tuberculosis/diagnosis/drug therapy/epidemiology MH - Mass Screening MH - Randomized Controlled Trials as Topic MH - *Tuberculosis/diagnosis/drug therapy/epidemiology MH - Tumor Necrosis Factor-alpha COIS- R. D. received a grant by the Niedersachsischer Verein zur Bekampfung der Tuberkulose, Lungen- und Bronchialerkrankungen.M. F. has worked as a paid consultant or speaker for the following companies: Novartis, LEO Pharma, Almirall and AbbVie.C. K. has consulted or lectured for AbbVie, Centogene, Celltrion, Chugai, Gilead, GSK, Janssen, Lilly, Medac, MSD, Novartis, Pfizer, Roche, Sanofi and UCB.U. M. has been a paid consultant and/or speaker and/or recipient of research support and/or participant in clinical trials for AbbVie, Almirall, Eli Lilly, Formycon, Janssen, LEO Pharma and Novartis.R. O.-K. has received fees from Novartis, Gilead, Boehringer Ingelheim, Berlin Chemie, Insmed and Astra Zeneca for lectures that were financially supported or organized by the companies mentioned.T. B., B. H., A. K., A. N. and T. S. do not declare any conflict of interest. EDAT- 2021/02/19 06:00 MHDA- 2021/04/22 06:00 CRDT- 2021/02/18 06:16 PHST- 2021/02/19 06:00 [pubmed] PHST- 2021/04/22 06:00 [medline] PHST- 2021/02/18 06:16 [entrez] AID - 10.1055/a-1294-1580 [doi] PST - ppublish SO - Pneumologie. 2021 Apr;75(4):293-303. doi: 10.1055/a-1294-1580. Epub 2021 Feb 17.