Evaluation of Tuberculosis Risk under Interleukin-1 Inhibitor Agents in Patients with Autoinflammatory Diseases: Experience from a Region with Moderate Tuberculosis Prevalence

Abstract

Background We aimed to investigate the rate of TBC reactivation in patients with autoinflammatory conditions who had been followed up under treatment with IL-1 antagonists in our clinic. We further aimed to evaluate whether latent TBC screening and isoniazid prophylaxis before IL-1 inhibitor treatment is beneficial in the prevention of reactivation.

Patients and Methods This study was designed as a cross-sectional and observational study. It received the approval of the local ethics committee and was therefore performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments. Adult patients who had been followed up in our clinic under treatment with IL-1 antagonists were evaluated with regard to whether they had a TBC infection before and after these treatments and whether they had been screened for latent TBC infection before IL-1 antagonist treatment and received prophylaxis. Clinical and laboratory data were obtained from hospital records and via telephone interviews after the patients had given their verbal consent to participate.

Results Fifty-nine patients under IL-1 antagonists were consecutively enrolled. 58 were under follow-up with the diagnosis of familial Mediterranean fever and one patient with a diagnosis of adult-onset Still’s disease. 35 patients (59.3%) were treated with anakinra and 24 (40.7%) were treated with canakinumab. 12 (50%) of the canakinumab users had previously received anakinra treatment and were switched to canakinumab due to side-effects or ineffectiveness. The number of patients who underwent latent tuberculosisc infection (LTBI) screening before treatment was 37 (62.7%); the number of patients who received prophylaxis was 13 (22%). None of the patients receiving IL-1 antagonists developed active tuberculosis.

Conclusion Blocking the IL-1 pathway may be safe regarding the activation of LTBI or development of a new tuberculosis infection even in locations with a high geographical risk.

Key words

tuberculosis - familial Mediterranean fever - reactivation - autoinflammatory - interleukin-1

Schlüsselwörter

tuberkulose - familiäres Mittelmeerfieber - interleukin 1 - reaktivierung - autoinflammatorisch

• References

• 1 Kastner DL, Aksentijevich I, Goldbach-Mansky R. Autoinflammatory disease reloaded: a clinical perspective. Cell 2010; 140: 784-790
• 2 Cavalli G, Dinarello CA. Anakinra therapy for non-cancer inflammatory diseases. Frontiers in pharmacology 2018; 9: 1157
• 3 [Anonym]. Anakinra. US Food and Drug Administration (FDA) approved product information. Revised December 2012. US FDA.
• 4 [Anonym]. Anakinra. European Medicines Agency (EMA) Summary of product characteristics. Last updated March 14, 2019. European Medicines Agency
• 5 [Anonym]. Canakinumab. US Food and Drug Administration (FDA) approved product information. Revised September 2016. US Food and Drug Administration
• 6 [Anonym]. Canakinumab. European Medicines Agency (EMA) Summary of product characteristics. Last updated February 25, 2020. European Medicines Agency
• 7 Anton Pozniak M, FRCP. Clinical manifestations and complications of pulmonary tuberculosis. uptodatecom last updated: Oct 25, 2019
• 8 Brassard P, Kezouh A, Suissa S. Antirheumatic drugs and the risk of tuberculosis. Clinical Infectious Diseases 2006; 43: 717-722
• 9 Settas LD, Tsimirikas G, Vosvotekas G. et al. Reactivation of pulmonary tuberculosis in a patient with rheumatoid arthritis during treatment with IL-1 receptor antagonists (anakinra). JCR: Journal of Clinical Rheumatology 2007; 13: 219-220
• 10 Migkos MP, Somarakis GA, Markatseli TE. et al. Tuberculous pyomyositis in a rheumatoid arthritis patient treated with anakinra. Clin Exp Rheumatol 2015; 33: 734-736
• 11 Lopalco G, Vitale A, Iannone F. et al. Anakinra long-term efficacy and safety in the management of Schnitzler’s syndrome and latent tuberculosis infection. Clinical and experimental rheumatology 2016; 34: 353-353
• 12 Mantovani A, Dinarello CA, Molgora M. et al. Interleukin-1 and related cytokines in the regulation of inflammation and immunity. Immunity 2019; 50: 778-795
• 13 Ravesloot-Chávez MM, Van Dis E, Stanley SA. The Innate Immune Response to Mycobacterium tuberculosis Infection. Annu Rev Immunol 2021; 39: 611-637
• 14 Yamashiro LH, Eto C, Soncini M. et al. Isoniazid-induced control of Mycobacterium tuberculosis by primary human cells requires interleukin-1 receptor and tumor necrosis factor. European Journal of Immunology 2016; 46: 1936-1947
• 15 Winthrop KL, Mariette X, Silva JT. et al. ESCMID Study Group for Infections in Compromised Hosts (ESGICH) Consensus Document on the safety of targeted and biological therapies: an infectious diseases perspective (Soluble immune effector molecules [II]: agents targeting interleukins, immunoglobulins and complement factors). Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases 2018; 24: S21-S40
• 16 Guler R, Parihar SP, Spohn G. et al. Blocking IL-1α but not IL-1β increases susceptibility to chronic Mycobacterium tuberculosis infection in mice. Vaccine 2011; 29: 1339-1346
• 17 Hossain MM, Norazmi MN. Pattern recognition receptors and cytokines in Mycobacterium tuberculosis infection-the double-edged sword?. Biomed Res Int 2013; 2013: 179174
• 18 Cantarini L, Lopalco G, Caso F. et al. Effectiveness and tuberculosis-related safety profile of interleukin-1 blocking agents in the management of Behçet’s disease. Autoimmunity Reviews 2015; 14: 1-9
• 19 Howard C, Noe A, Skerjanec A. et al. Safety and tolerability of canakinumab, an IL-1β inhibitor, in type 2 diabetes mellitus patients: a pooled analysis of three randomised double-blind studies. Cardiovascular diabetology 2014; 13: 1-16
• 20 Everett BM, MacFadyen JG, Thuren T. et al. Inhibition of interleukin-1β and reduction in atherothrombotic cardiovascular events in the CANTOS trial. Journal of the American College of Cardiology 2020; 76: 1660-1670
• 21 Sundy JS, Schumacher HR, Kivitz A. et al. Rilonacept for gout flare prevention in patients receiving uric acid-lowering therapy: results of RESURGE, a phase III, international safety study. The Journal of rheumatology 2014; 41: 1703-1711
• 22 Grayson PC, Yazici Y, Merideth M. et al. Treatment of mucocutaneous manifestations in Behçet’s disease with anakinra: a pilot open-label study. Arthritis research & therapy 2017; 19: 1-7
• 23 Schnappauf O, Chae JJ, Kastner DL. et al. The pyrin inflammasome in health and disease. Frontiers in immunology 2019; 10: 1745
• 24 Bilginer Y, Ayaz NA, Ozen S. Anti-IL-1 treatment for secondary amyloidosis in an adolescent with FMF and Behçet’s disease. Clinical rheumatology 2010; 29: 209-210
• 25 Goletti D, Petrone L, Ippolito G. et al. Preventive therapy for tuberculosis in rheumatological patients undergoing therapy with biological drugs. Expert Review of Anti-Infective Therapy 2018; 16: 501-512
• 26 Sibley CH, Plass N, Snow J. et al. Sustained response and prevention of damage progression in patients with neonatal-onset multisystem inflammatory disease treated with anakinra: a cohort study to determine three-and five-year outcomes. Arthritis & Rheumatism 2012; 64: 2375-2386
• 27 Kullenberg T, Löfqvist M, Leinonen M. et al. Long-term safety profile of anakinra in patients with severe cryopyrin-associated periodic syndromes. Rheumatology 2016; 55: 1499-1506