Elsevier

Autoimmunity Reviews

Volume 14, Issue 6, June 2015, Pages 503-509
Autoimmunity Reviews

Review
Guidance for the management of patients with latent tuberculosis infection requiring biologic therapy in rheumatology and dermatology clinical practice

https://doi.org/10.1016/j.autrev.2015.01.011Get rights and content

Highlights

  • Guidance for LTBI detection and active TB prevention before biologic starting

  • Evidence on host-, traditional DMARD-, and single biologic-related TB risk

  • Stratification of LTBI patients in low, intermediate, and high TB risk categories

  • Guidance for the safest biologic choice in patient with LTBI

  • Guidance for the management of patients with RA, PsA, AS, and Pso with active TB

Abstract

Since the introduction of biologics for the treatment of rheumatoid arthritis (RA), psoriatic arthritis (PsA), ankylosing spondylitis (AS), and psoriasis (Pso) an increased risk of tuberculosis (TB) reactivation in patients with latent tuberculosis infection (LTBI) has been recorded for anti-TNF agents, while a low or absent risk is associated with the non-anti-TNF targeted biologics. To reduce this risk several recommendation sets have been published over time, but in most of them the host-related risk, and the predisposing role to TB reactivation exerted by corticosteroids and by the traditional disease-modifying anti-rheumatic drugs has not been adequately addressed. Moreover, the management of the underlying disease, and the timing of biologic restarting in patients with TB occurrence have been rarely indicated. A multidisciplinary expert panel, the Italian multidisciplinary task force for screening of tuberculosis before and during biologic therapy (SAFEBIO), was constituted, and through a review of the literature, an evidence-based guidance for LTBI detection, identification of the individualized level of risk of TB reactivation, and practical management of patients with TB occurrence was formulated. The literature review confirmed a higher TB risk associated with monoclonal anti-TNF agents, a low risk for soluble receptor etanercept, and a low or absent risk for non-anti-TNF targeted biologics. Considering the TB reactivation risk associated with host demographic and clinical features, and previous or current non-biologic therapies, a low, intermediate, or high TB reactivation risk in the single patient was identified, thus driving the safest biologic choice. Moreover, based on the underlying disease activity measurement and the different TB risk associated with non-biologic and biologic therapies, practical indications for the treatment of RA, PsA, AS, and Pso in patients with TB occurrence, as well as the safest timing of biologic restarting, were provided.

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.

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