ReviewGuidance for the management of patients with latent tuberculosis infection requiring biologic therapy in rheumatology and dermatology clinical practice
Introduction
Over the last 15 years biologic drugs have ensured relevant advantages in rheumatology and dermatology for the treatment of rheumatoid arthritis (RA), ankylosing spondylitis (AS), psoriatic arthritis (PsA), and psoriasis (Pso). To date, several agents with pharmacological activity targeted on different levels of immune response are available in clinical practice, including interleukin-6 inhibitor tocilizumab (TCZ), anti-CD20 rituximab (RTX), anti-interleukin-1 anakinra (ANK), anti-CD28 abatacept (ABA), anti-IL12-23 ustekinumab (UTK), and anti-tumor necrosis factor alpha agents (anti-TNFα) including adalimumab (ADA), etanercept (ETN), infliximab (IFX), golimumab (GOL), and certolizumab (CTP).
However, data from clinical trials and from real-life clinical practice have shown that currently used biologics, namely the anti-TNFα and to a lesser extent the non-anti-TNFα targeted agents, may constitute a risk factor for tuberculosis (TB) reactivation in subjects with latent TB infection (LTBI) [1], [2]. Hence, LTBI screening and prevention of active TB represent a current worldwide challenge for biologic prescribers.
To reduce the risk of TB reactivation several sets of recommendations and guidelines have been proposed, but none of them may be appropriate for the single country due to the different social and economic conditions and the variable prevalence of TB [3]. The majority of recommendations/guidelines have been prompted for patients to be treated with the oldest anti-TNFα, namely IFX, ETN and ADA, while no policy document is available for the more recently marketed biologics such as GOL, CTP, TCZ, RTX, ABA, and UTK.
In addition, most of the current recommendations raise some concerns because they do not take in account the specific risk related to the host and to the previous or current treatments, and only two sets have been formulated through a multidisciplinary approach [4], [5]. Furthermore, although biologics are loaded by a different TB risk, none of the recommendations provide indications for choosing the proper biologic treatment in function of the specific risk associated with the single patient. Finally, details concerning the management of the underlying rheumatic disease or Pso in case of active TB occurrence have been rarely indicated [6].
Section snippets
Objective
To provide an evidence-based algorithm for the detection of LTBI and prevention of TB reactivation, to examine the clinical variables, including the host-related, the traditional disease modifying anti-rheumatic drug (DMARD)-related, and the single biologic agent-related TB risk, that may influence the therapeutic choice in LTBI positive patients with RA, PsA, AS, and Pso requiring biologic therapy, and to suggest practical indications for the management of the patients with active TB
SAFEBIO expert panel purpose
A multidisciplinary expert panel, the Italian multidisciplinary task force for screening of tuberculosis before and during biologic therapy (SAFEBIO), including specialists in rheumatology (FC, CN, LN, FI), microbiology (GD), radiology (GG), pneumology (ASZ), immunology (AM), dermatology (FP), epidemiology (MC), and infectious diseases (DG), was constituted to perform a systematic literature review on the existing recommendations for LTBI screening before biologic starting and overtime
SAFEBIO evidence-based guidance for LTBI screening procedures and active TB prophylaxis
LTBI screening procedures are mandatory before biologic starting. A full clinical history and physical examination should be part of the initial assessment. This should include details of ethnicity, country of birth, history of recent exposure to TB, previous active TB and treatment completion, together with any additional risk such as drug or alcohol abuse [7]. Fig. 1 shows the SAFEBIO recommendations in BCG-unvaccinated and -vaccinated subjects. These recommendations have been developed on
Conclusion
Biologics are characterized by different molecular structure and pharmacologic target with relevant differentiation concerning the risk of TB reactivation. Hence, clinicians should properly screen for LTBI the patients with RA, PsA, As, and Pso who are candidates for biologic therapy, and LTBI subjects need to be properly assessed for different risk factors related to the host demographic and comorbidity features and to the previous or current immunosuppressive therapies.
Based on the literature
Take-home messages
- •
The risk associated with the demographic characteristics, the presence of comorbidities, the previous or current non-biologic drug exposure, and the different predisposing roles of biologics should be evaluated in patients with RA, PsA, AS, and Pso who are positive for LTBI and require biologic therapies.
- •
Through an evidence-based approach, LTBI positive patients may be categorized as at low, intermediate, and high risk of TB reactivation, with consequent reflexes on the choice of the safest
Conflict of interests
The authors declare no conflict of interests.
References (71)
- et al.
Biologic registries in rheumatology: lessons learned and expectations for the future
Autoimmun Rev
(2012) - et al.
Adjustment of therapy in rheumatoid arthritis on the basis of achievement of stable low disease activity with adalimumab plus methotrexate or methotrexate alone: the randomised controlled OPTIMA trial
Lancet
(2014) - et al.
The use of biosimilars in immune-mediated disease: a joint Italian Society of Rheumatology (SIR), Italian Society of Dermatology (SIDeMaST), and Italian Group of Inflammatory Bowel Disease (IG-IBD) position paper
Autoimmun Rev
(2014) - et al.
Effectiveness and tuberculosis-related safety profile of interleukin-1 blocking agents in the management of Behçet's disease
Autoimmun Rev
(2015) - et al.
Tocilizumab monotherapy versus adalimumab monotherapy for treatment of rheumatoid arthritis (ADACTA): a randomised, double-blind, controlled phase 4 trial
Lancet
(2013) - et al.
Efficacy and safety of ustekinumab in patients with active psoriatic arthritis: 1 year results of the phase 3, multicentre, double-blind, placebo-controlled PSUMMIT 1 trial
Lancet
(2013) - et al.
Long-term follow-up of patients with tuberculosis as a complication of tumour necrosis factor (TNF)-alpha antagonist therapy: safe re-initiation of TNF-alpha blockers after appropriate anti-tuberculous treatment
Clin Microbiol Infect
(2008 Feb) - et al.
Are patients with rheumatoid arthritis still at an increased risk of tuberculosis and what is the role of biological treatments?
Ann Rheum Dis
(2014) - et al.
Risk of tuberculosis in patients with chronic immune-mediated inflammatory diseases treated with biologics and tofacitinib: a systematic review and meta-analysis of randomized controlled trials and long-term extension studies
Rheumatology (Oxford)
(2014) - et al.
Diagnosis of latent tuberculosis and prevention of reactivation in rheumatic patients on biologic therapy: the international recommendations
J Rheumatol Suppl
(2014)