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Published on: September 5, 2017
Joint Statement (DZK, DGRh, DDG) on the Tuberculosis Risk with Treatment Using Novel Non-TNF-Alpha Biologicals
R Diel1,2,3, T Schaberg3, A Nienhaus4,5
1Institute for Epidemiology, University Medical Hospital Schleswig-Holstein, Campus Kiel, Germany. Member of the German Center for Lung Research (ARCN).
Background:
While the risk of tuberculosis (TB) reactivation is adequately documented in relation to TNF-alpha inhibitors (TNFi), the question of what the tuberculosis risk is for newer, non-TNF biologics (non-TNFi) has not been thoroughly addressed.
Methods:
We conducted a systematic review of randomized phase 2 and phase 3 studies, and long-term extensions of same, published through March 2019. Of interest was information pertaining to screening and treating of latent tuberculosis (LTBI) in association with the use of 12 particular non-TNFi. Only rituximab was excluded. We searched MEDLINE and the ClinicalTrial.gov database for any and all candidate studies meeting these criteria.
Results:
677 citations were retrieved; 127 studies comprising a total of 34,293 patients who received non-TNFi were eligible for evaluation. Only 80 out of the 127 studies, or 63 %, captured active TB (or at least opportunistic diseases) as potential outcomes and 25 TB cases were reported. More than two thirds of publications (86/127, 68 %) mentioned LTBI screening prior to inclusion of study participants in the respective trial, whereas in only 4 studies LTBI screening was explicitly considered redundant. In 21 studies, patients with LTBI were generally excluded from the trials and in 42 out of the 127 trials, or 33 %, latently infected patients were reported to receive preventive therapy (PT) at least 3 weeks prior to non-TNFi treatment.
Conclusions:
The lack of information in many non-TNFi studies on the number of patients with LTBI who were either excluded prior to participating or had been offered PT hampers assessment of the actual TB risk when applying the novel biologics. Therefore, in case of insufficient information about drugs or drug classes, the existing recommendations of the German Central Committee against Tuberculosis should be applied in the same way as is done prior to administering TNFi. Well designed, long-term "real world" register studies on TB progression risk in relation to individual substances for IGRA-positive cases without prior or concomitant PT may help to reduce selection bias and to achieve valid conclusions in the future.
Insights
The risk of tuberculosis (TB) reactivation with non-tumor necrosis factor inhibitors (non-TNFi) is unclear due to limited data on latent TB infection (LTBI) screening and preventive therapy (PT). Further real-world studies are needed to assess TB risk with these novel biologics.
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.
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