Table 1.
Risk of tuberculosis associated with TNF-α inhibitor treatment
| Drug | Study details | Outcomes | Reference |
|---|---|---|---|
| Infliximab | Analysis of reports of TB in the FAERS MedWatch program from 1998 to May 29, 2001(http://www.fda.gov/cder/aers/) | 70 reported cases of TB after treatment with infliximab for a median of 12 weeks; in 48 patients, TB developed after ≤3 infusions; 40 patients had extrapulmonary disease | 10 |
| Infliximab, adalimumab, both | 873 IBD subjects treated with TNF-α inhibitors from January 2001 to December 2013 | 25 newly developed TB cases; adjusted SIR, 41.7 (95% CI: 25.3–58.0%); 19 patients developed TB within 2–62 months of treatment initiation; treatment with infliximab was a significant predictor of TB (P=0.033) | 12 |
| Infliximab, adalimumab | Retrospective analysis of serious infections within 6 months of initiation of TNF-α inhibitor therapy | TB occurred in 3/175 patients; none treated with anti-TB chemoprophylaxis prior to treatment with TNF-α inhibitor | 13 |
| Infliximab, adalimumab, etanercept | Incidence study and case-control analysis to determine risk of TB in patients treated with TNF-α inhibitor in the French RATIO registry over 3 years | No patient received anti-TB chemoprophylaxis; overall adjusted SIR (95% CI), 12.2 (9.7–15.5%); for infliximab, 18.6 (13.4–25.8%); adalimumab, 29.3 (20.3–42.4%); etanercept, 1.8 (0.7–4.3%); treatment with infliximab or adalimumab versus etanercept was an independent risk factor for TB with OR (95% CI) 13.3 (2.6–69.0%) and 17.1 (3.6–80.6%), respectively | 14 |
| Infliximab, adalimumab, etanercept | Review of medical records from 2002 to 2009 among patients with AS treated with other agents (n=919) or TNF-α inhibitors (n=354) for new cases of TB; reference data from the Korean National Tuberculosis Association | Mean TB incidence rate per 100,000 PY =69.8 in general population versus 308 in AS patients treated with other agents versus 561 in AS patients treated with TNF-α inhibitors. Incidence rates for infliximab, 540; adalimumab, 490; etanercept, 0 | 18 |
| TNF-α inhibitors | Retrospective analysis of 949 patients treated with TNF-α inhibitors at the Yonsei University Health System from 2005 to 2012 evaluating incidence of active TB between LTBI-positive (n=256) and -negative patients (n=521) | Active TB incidence rate per 100,000 PY =1,107 in LTBI-positive patients; 490 in LTBI-negative patients | 19 |
| TNF-α inhibitors | Literature review of articles published in PubMed from January 2000 to October 2011 and data from China Hospital Knowledge Database; RA and AS patients from Africa, Middle East, and Asia | Risk for active TB and other infections increased in patients receiving TNF-α inhibitors; risk is higher among those treated with monoclonal antibodies versus soluble TNF-α receptor | 15 |
| Infliximab, adalimumab, etanercept | ARI of TB was estimated using published SIR from the French RATIO registry and incidence of TB. The NNH for each TNF-α inhibitor and the NNT to reduce 1 TB event using etanercept instead of adalimumab or infliximab were calculated | The ARI of TB with anti-TNF-α therapies in Asian countries is substantially higher than Western Europe and North America. NNH ranges were 8–163 for adalimumab, 126–2,646 for etanercept, and 12–256 for infliximab. The NNT to reduce 1 TB event using etanercept instead of adalimumab ranged from 8 to 173 and using etanercept instead of infliximab from 13 to 283 | 20 |
| Adalimumab, etanercept | Retrospective cohort study on RA patients treated with TNF-α inhibitors from 2006 to 2008 using data from Taiwan’s National Health Insurance claims databases. Primary outcome: active TB; TB risk estimated using Cox’s proportional hazard model | Active TB rates per 100,000 PY were 1,411.3 for patients treated with adalimumab and 679.5 for patients treated with etanercept. Patients treated with TNF-α inhibitors had a higher risk of TB (aHR 4.87 [95% CI: 2.14–11.06%]) | 16 |
Abbreviations: aHR, adjusted hazard ratio; ARI, absolute risk increase; AS, ankylosing spondylitis; CI, confidence interval; IBD, inflammatory bowel disease; LTBI, latent TB infection; NNH, number needed to harm; NNT, number needed to treat; OR, odds ratio; PY, patient year(s); RA, rheumatoid arthritis; SIR, standardized incidence ratio; TB, tuberculosis; TNF-α, tumor necrosis factor-α.