Background
Tuberculosis preventive treatment (TPT) has been recognized by the World Health Organization as a critical intervention to eliminate tuberculosis. Rifampin TPT is critical to this goal, given high completion rates, short treatment lengths, and low side-effects. However, rifampin treatment has limitations by drug-drug interactions (DDI) with multiple medications
Methods
A post-hoc data analysis from the 2R2 trial (Ruslami,R Lancet Resp Med 2024) on comorbidity and concomitant medications of all participants was obtained before starting TPT. Information on side effects and concomitant medication adjustments were asked at each study visit. The study population was classified as taking at least one “essential” concomitant medication or not. Essential medications were defined as 1) prescribed by a doctor; 2) could not be interrupted for the treatment duration with Rifampin 3) if interrupted would have caused potentially life threatening or debilitating consequences. We then analyzed essential medications in categories B to X, by mechanism of action for Rifampin DDI, using Lexi-drugs database
Results
1368 participants were in the 2R2 study; 282 (21%) were classified as taking at least one concomitant “essential” medication with possible interaction with rifampin, almost half (n=128, 45%) took > 2 essential medications. 198 participants (70%) in the DDI population completed TPT treatment, with no significant differences in completion compared to the non-DDI population. Participants who took at least one dose of TPT, an adverse event (AE) resulting in permanent treatment discontinuation (protocol-defined AE) was reported for 27 (9.9%) participants in the DDI population and 58 (5.6%) in the non-DDI population. Most frequent AE, rash/allergy had similar distribution in the two populations (3%), while GI intolerance was more common in DDI population (3% vs. 1%). At follow-up, the proportion of participants who required additional unscheduled visits was higher in the DDI population and the time to the first additional visit was significantly shorter. More participants in the DDI population reported more than one symptom at the second scheduled follow-up visit (GI intolerance was most reported)
Conclusions
This demonstrates that DDI(s) with rifampin can be managed safely without impacting TPT completion rates of standard and high dose. Participants taking concomitant medications with possible rifampin DDI required increased clinical monitoring to achieve similar outcomes to the non-DDI population