(Re-)introduction of TNF antagonists and JAK inhibitors in patients with previous tuberculosis: a systematic review

Background: Tuberculosis (TB) is a common complication associated with treatment with tumour necrosis factor (TNF) antagonists and Janus kinase (JAK) inhibitors. However, there is uncertainty about the risk of TB relapse in patients with TB and comorbidities requiring treatment with these agents. Objectives: To assess the risk of TB relapse in patients (re-)started on TNF antagonists or JAK inhibitors. Methods: Systematic review. Data sources: PubMed and Cochrane Library databases until 11 December 2023. Study eligibility criteria: Randomized control trials, prospective and retrospective cohort studies, case reports and case series. Participants: Patients with current or previous TB who were (re-)started on TNF antagonists or JAK inhibitors. Interventions: (Re-)introduction of TNF antagonists and JAK inhibitors. Assessment of risk of bias: All studies meeting entry criteria were included regardless of quality. Methods of data synthesis: Categorical data are presented as frequencies and percentages. For non-normally distributed aggregated data, we calculated the pooled weighted median with 95% CI. For individual patient data, the median and interquartile range (IQR) were calculated. Results: Of 5018 articles screened for eligibility, 67 publications reporting on 368 TB patients who (re-) initiated treatment with TNF antagonists for underlying diseases were included. The median age was 42.5 years (95% CI: 40.4-42.5) and the proportion of female patients was 36.6% (n = 74) of patients whose sex was reported. A total of 14 patients (3.8%, 95% CI: 2.1-6.3%) developed TB relapse after a median of 8.5 months (interquartile range, 6.8-14.8 months) following (re-)initiation of anti-TNF treatment. Furthermore, among 251 articles screened for eligibility, 11 reports on TB patients who were (re-)started on JAK inhibitors for underlying diseases were identified. The median age was 62 years (interquartile range, 48.5-68.5 years) and 45.5% (n = 5) were female. Only one patient (9.1%; 95% CI: 0.2-41.3%) had TB reactivation 10 months after starting treatment with ruxolitinib. In addition, 94 patients who were treated with TNF antagonists and two patients temporarily treated with JAK inhibitors for the prevention or treatment of paradoxical reactions were analysed. None of the publications reported microbiological failure or worsening of TB-related symptoms. Conclusions: (Re-)initiation of TNF antagonists and JAK inhibitors may be relatively safe in patients with current or previous TB and the need for further treatment of underlying diseases. Thomas Theo Brehm, (c) 2024 The Authors. Published by Elsevier Ltd on behalf of European Society of Clinical Microbiology and Infectious Diseases. This is an open access article under the CC BY-NC-ND license (http:// creativecommons.org/licenses/by-nc-nd/4.0/).