In those talking 3HP for LTBI, female sex, an age from 45 to 54 years, and use of concomitant medications were significantly linked to SDRs and discontinuing treatment.
A regimen of 3 months of weekly rifapentine plus isoniazid (3HP) is safe and well-tolerated in patients with latent tuberculosis infection (LTBI), according to a study in Clinical Infectious Diseases.
Although 3HP for LTBI is recommended worldwide, associated symptoms and systemic drug reactions (SDRs) are not fully characterized. Investigators therefore assessed patients taking 3HP to explore patterns of SDR symptom development and factors related to SDRs. To accomplish this, the researchers analyzed SDR symptom data from the iAdhere trial (ClinicalTrials.gov Identifier: NCT01582711), which prospectively obtained data on the symptoms of concern that were seen in the PREVENT TB trial (ClinicalTrials.gov Identifier: NCT00023452) of adults taking 3HP for LTBI.
Collecting data on SDRs was a secondary objective of the open-label, randomized iAdhere clinical trial, which had the primary objective of comparing 3HP treatment completion rates in those with direct-observed therapy vs self-administered therapy. The trial was conducted from September 2012 to April 2014 in the US, Spain, Hong Kong, and South Africa. Trial participants’ symptoms were assessed and graded during scheduled visits at baseline, 4, 8, and 12 weeks after treatment initiation (and at 16-week visits for those who did not complete treatment in 12 weeks), as well as at 28 days after the final treatment dose. Patient symptoms were self-reported for those that occurred since the previous visit.
For the current analysis, researchers assessed the incidence and factors associated with SDRs and patients’ development of individual symptoms while receiving 3HP treatment, regardless of SDR. The outcomes of interest in bivariate and multivariable analyses were a category I or II SDR and discontinuation of 3HP treatment.
The analysis included 1002 patients (median age, 36 years [interquartile range, 27-49 years; 48% female; 52% White). Of the cohort, 768 (77%) participants reported at least 1 symptom during study treatment, with most reported during a routine study visit (81%) vs an unscheduled visit (19%). At the scheduled visits, 4842 symptoms were graded, and a majority were mild (grade 1, n=4071 [84%]) or moderate (grade 2, n=669 [14%]).
Among the patients who had a symptom when receiving 3HP (n=768), 622 (81%) completed treatment without discontinuing, and 146 (19%) participants did not complete treatment for any reason.
A total of 111 (11%) participants reported symptoms that met an SDR definition. Among these symptoms, 16 (1.6% of all participants) met category I criteria and 95 (9.5%) were in category II. Notably, 5 participants in category I also met criteria for category II. The patients meeting category I SDR criteria had hypotension (n=2), hives (n=8), angioedema (n=1), wheezing/acute bronchospasm (n=1), or conjunctivitis/red eyes (n=4). The most frequently occurring symptoms for category II SDRs were fatigue (n=75; 79%), headache (n=66; 69%), nausea (n=61; 62%), and aches (n=60; 63%).
Symptoms for SDRs were recorded during unscheduled visits for 64 participants (58%) and at scheduled visits for 47 participants (42%). Almost one-half (48%) of participants who met criteria for SDRs completed treatment.
Multivariable regression analysis demonstrated that female sex (risk ratio [RR], 2.05; 95% CI, 1.19-3.54), ages of 45 to 54 years (RR, 1.99; 95% CI, 1.19-3.31), and use of concomitant medications (RR, 2.26; 95% CI, 1.15-4.42) had a statistically significant association with SDRs and discontinuation.
Participants with an SDR (84%; 93/111) used concomitant medications more frequently compared with those without an SDR (53%; 473/891).
Among several limitations, participants self-reported symptoms that occurred between their current and previous visits, and the researchers were unable to identify why treatment was discontinued for those who reported SDRs. In addition, most patients were White (52%) and not born in a country with a high TB prevalence.
“Future studies are warranted to understand how to prevent or manage symptoms, including those indicative of SDRs, in patients taking 3HP, to maximizing LTBI treatment completion,” stated the investigators. “Further efforts are also needed to develop additional, shortened LTBI treatment regimens that are even better tolerated in the future.”
Disclosure: Pharmaceutical support was provided by Sanofi. Please see the original reference for a full list of disclosures.
References:
Sadowski C, Belknap R, Holland DP, et al. Symptoms and systemic drug reactions in persons receiving weekly rifapentine plus isoniazid (3HP) treatment for latent tuberculosis infection. Clin Infect Dis. Published online February 23, 2023. doi:10.1093/cid/ciad083
Source: Pulmonology Advisor