Risk of tuberculosis reactivation associated with traditional disease modifying anti-rheumatic drugs and non-anti-tumor necrosis factor biologics in patients with rheumatic disorders and suggestion for clinical practice

ABSTRACT

Introduction: Two classes of biologics, anti-tumor necrosis factor (TNF) and non-anti-TNF targeted, are currently available for the treatment of rheumatic diseases.

Areas covered: Discussion on the need for LTBI diagnosis in rheumatic patients treated csDMARDs and non-anti-TNFs through a review of the literature. The literature, updated to 15 April 2019, on tuberculosis (TB) reactivation risk in patients exposed to conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) and non-anti-TNF biologics was reviewed.

Expert opinion: An increased risk of TB reactivation in patients receiving csDMARDs (except sulphasalazine) resulted, while a review of clinical trials, and Periodic Safety Update Reports from pharmaceutical Companies evidenced a very low or absent risk for non-anti-TNF biologics. Hence, a contradiction emerges considering that latent TB infection (LTBI) screening is recommended for non-anti-TNF candidates but not for csDMARDs. Concerning the low TB incidence countries, several actions could be undertaken, including to screen all patients independently on the treatment, to omit the procedure in non-anti-TNF candidates, or to perform the LTBI investigations only in high-risk patients. According to WHO guidelines, LTBI screening in low TB risk countries seems unnecessary, except in high TB risk subjects.

KEYWORDS:

• LTBI
• non-anti-TNF biologics
• tuberculosis
• csDMARDs

Article highlights

• LTBI screening procedures are currently recommended before starting anti-TNF and non-anti-TNF biologics.

• Current evidence shows that no increased risk of TB reactivation is associated with non-anti-TNF targeted biologics.

• Based on available studies, approved csDMARDs (except sulphasalazine) increase the risk of TB reactivation, but LTBI screening is not labeled for these drugs.

• Considering these data, several issues emerge as to whether the screening should be performed in all, or in none of the patients.

• According to WHO guidance, in low TB risk countries, both in csDMARD and non-anti-TNF candidates, LTBI screening might be limited to high-risk subjects.

• The strength of this statement is weakened by the absence of RCTs evaluating the TB risk associated with csDMARDs.

This box summarizes the key points contained in the article.

Acknowledgments

We are thankful to all Pharmaceutical Companies for providing us the Periodic Safety Update Reports of non-anti-TNF biologics.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.