Table 3.

Summary Data on TB Reactivation with the Use of Newer Biologic Therapies in Patients with IBD

Biologic	Publication	Type of study	Brief description	Country	Key findings
Vedolizumab	Bonovas et al. (2016)20	Meta-analysis	Meta-analysis of 49 RCTs, focused on risk of infections with biologics	NA	Odds of TB numerically higher with biologics vs placebo (OR, 2.04; 95% CI, 0.71–5.89). Results did not reach statistical significance.
					9 Cases (0.36%) of TB infection with biologics vs 1 (0.07%) with placebo.
	Luthra et al. (2015)58	Meta-analysis	Meta-analysis of 12 RCTs; focused on risk of infections with adhesion molecule antagonists	NA	Risk of opportunistic infection was not significantly higher either with non-gut-specific (RR, 2.34; 95% CI, 0.05–108.72) or gut specific drugs (RR, 1.55; 95% CI, 0.16–14.83), compared to placebo.
					Only one case of TB was identified.
	Ng et al. (2018)59	Review	Review on the risk of opportunistic infections with vedolizumab; safety data from the GEMINI 1, 2 & OLE studies and post-marketing data	NA	Clinical trials: 6 TB events in 5 patients (serious: n=4; non-serious: n=1), with 4 TB events considered treatment-related. Incidence rate 0.1 per 100 PY.
					Post-marketing: In ~114,071 PY, 7 patients reported TB (serious: n=5; non-serious: n=2).
	Colombel et al. (2017)60 (and Bye et al. [2017]61)	Review	Review of safety of vedolizumab; n=2,830; 4,811 PY exposure	NA	4 Reports of TB, i.e. 0.14% of patients.
					Of the 4, 3 had a negative LTBI screening and developed pulmonary TB (considered to be primary infections); 1 developed LTBI.
	Amiot et al. (2016)62	Review	Review of safety and efficacy of vedolizumab in IBD	NA	One patient developed TB despite a negative LTBI screening.
Ustekinumab	Cantini et al. (2017)63	Review	Review of TB reactivation risk in RA, AS and PsA	NA	No cases of active TB reported in 3 clinical trials, both short-term and after 2 years of treatment.
					Across 5 trials in psoriasis and PsA, no active TB in 167 patients who were positive for LTBI.
					No TB cases in 3,474 patients in the Psoriasis Longitudinal Assessment and Registry over median 1.60 years follow-up.
Tofacitinib	Winthrop et al. (2016)64	Review	Review of the risk of opportunistic infections with tofacitinib in RA	NA	Within the global tofacitinib RA development program, TB was seen in 26 of 5,671 subjects, with a crude incidence rate of 0.21 per 100 PY (95% CI, 0.14–0.30).
	Cohen et al. (2018)65	PMS data	Review of worldwide tofacitinib PMS data in RA	NA	During a 3-year reporting period covering 34,223 PY, 4,352 SAEs were reported, of which there were 6 TB SAEs.

TB, tuberculosis; IBD, inflammatory bowel disease; RCT, randomized controlled trial; NA, not applicable; OR, odds ratio; CI, confidence intervals; RR, relative risk; OLE, open label extension; PY, person-year; LTBI, latent tuberculosis infection; RA, rheumatoid arthritis; AS, ankylosing spondylitis; PsA, psoriatic arthritis; PMS, post-marketing surveillance; SAE, serious adverse event.