Joint Statement (DZK, DGRh, DDG) on the Tuberculosis Risk with Treatment Using Novel Non-TNF-Alpha Biologicals.

Area of Science:

• Immunology
• Rheumatology
• Infectious Diseases

Background:

• The risk of tuberculosis (TB) reactivation is well-documented for TNF-alpha inhibitors (TNFi).
• However, the TB risk associated with newer, non-TNF biologics (non-TNFi) remains less understood.
• This study addresses the knowledge gap regarding TB risk with non-TNFi therapies.

Purpose of the Study:

• To systematically review the literature on tuberculosis risk in patients treated with non-TNFi.
• To evaluate the reporting of latent tuberculosis infection (LTBI) screening and preventive therapy (PT) in clinical trials of non-TNFi.
• To identify gaps in data that hinder the assessment of TB risk with novel biologics.

Main Methods:

• A systematic review of randomized phase 2 and 3 studies (and extensions) of 12 non-TNFi (excluding rituximab) published through March 2019.
• Searches were conducted in MEDLINE and ClinicalTrials.gov.
• Data on LTBI screening, treatment, and active TB cases were extracted.

Main Results:

• 127 studies involving 34,293 patients treated with non-TNFi were included.
• Only 63% of studies captured active TB or opportunistic diseases as outcomes, reporting 25 TB cases.
• While 68% mentioned LTBI screening, only 33% reported preventive therapy for latently infected patients.

Conclusions:

• Incomplete reporting on LTBI screening and preventive therapy in non-TNFi studies complicates the assessment of actual TB risk.
• Existing recommendations for TNFi should be applied to non-TNFi in cases of insufficient data.
• Long-term, real-world studies are crucial for accurate TB risk assessment with individual non-TNFi, especially in IGRA-positive individuals without prior PT.