Side Effects and Completion Rates of Treatment Regimens for Latent Tuberculosis Infection: A Rapid Review with Network Meta-Analyses

The treatment of latent tuberculosis infection (LTBI) is a vital component of the overall strategy to reduce tuberculosis (TB) in a population. Treatment prevents ongoing transmission in communities by preventing the development of active TB disease. One of the greatest impediments to the treatment is the lengthy 9 month course of treatment with Isoniazid (INH), which is the current international standard. According to results of a few large randomized controlled trials Rifapentine and INH given once weekly for a total of 12 doses (3HP) given directly observed has been shown to be as effective as 9 months (252 doses) of daily INH self-administered for the treatment of LTBI. A preliminary literature search seeking reviews addressing the aspect of safety of competing regimens for LTBI did not identify any published articles. A full literature search has not been undertaken to determine if there are more published and non-published primary data sets, however those detailed here can play a very important role in establishing whether the new 3HP regimen should be approved for use in Nunavut. \n \nIn addition to adverse events, the proposed review would study an additional key outcome which is vital to establishing a new protocol in Nunavut: the number of patients that completed the 3HP regimen compared to other common regimens (i.e. the completion rate). This is of high importance given that a shortened regimen will facilitate treatment to prevent disease in a region where the rate of initiation of treatment for LTBI for the standard INH regimen is only 47%, and completion rates (of those that initiated the 78 dose regimen) are only 70%.7 In other words, for every 100 patients diagnosed with LTBI in this region, only 33 complete treatment. Therefore, we are currently missing the opportunity to treat almost two thirds of all persons diagnosed with LTBI in Iqaluit.\n \nKnowledge generated from a review addressing these considerations will inform key stakeholders in Nunavut trying to decide if the new 3HP regimen can be adopted in the Territory. If the results are favourable, the use of this regimen could significantly impact TB prevention in Nunavut where the incidence rates of active TB disease are the highest in Canada, and also in other Canadian Aboriginal communities facing similar challenges. This rapid review will directly inform practice in this area.\n \nThe objective of this review is to summarize the available evidence related to the rates of toxicities and completion rates for competing treatment regimens for latent tuberculosis infection (LTBI) of relevance to the province of Nunavut. We will also provide a narrative summary of the recent systematic reviews which have addressed efficacy of competing regimens for LTBI as supplemental information for decision making.\nThe questions addressed are as follow:\n1. Is the 3HP regimen for latent tuberculosis associated with similar or lesser rates of adverse reactions compared to the standard 252 dose INH (9 month daily) treatment currently used in Canada, 78 dose INH (9 month) treatment used in Nunavut, 180 dose INH (6 months daily), 3-4 months daily isoniazid and rifampin, and a 4-month regimen of Rifampin given daily for 4 months?\n2. Is the 3HP regimen for latent tuberculosis associated with greater rates of regimen completion compared to the standard 252 dose INH (9 month daily) treatment currently used in Canada, 78 dose INH (9 month) treatment used in Nunavut, 180 dose INH (6 months daily), 3-4 months daily isoniazid and rifampin, and a 4-month regimen of Rifampin given daily for 4 months?