A Leap Forward – All Oral Regimens Revolutionizing Multidrug-resistant Tuberculosis Treatment

All oral regimens have become a great advancement in the treatment of multidrug-resistant tuberculosis (MDR-TB). Earlier, the treatment of MDR-TB was considered long, with side effects and more relapse rate. The best estimate of the proportion of people diagnosed with MDR/Rifampicin-resistant TB (RR-TB) among newly diagnosed TB has remained at about 3%–4%, and among those diagnosed with previously treated TB has remained at about 18%–21% globally.[1] In 2023, India is among the first five countries which accounted for more than half of the global number of people estimated to have developed MDR/RR-TB. But the estimates of MDR/RR-TB in India have reduced by 20% from 1.49 lakh in 2015 to 1.10 lakh in 2023, with an estimated proportion of new TB cases with MDR/RR-TB at 2.5% and of previously treated TB cases with MDR/RR-TB at 13% as per the WHO Global TB Report 2024.[2,3] Treatment duration for MDR-TB depends on the regimen and the patient condition. All patients with MDR/RR-TB, including those with additional resistance to fluoroquinolones, need to benefit from effective all-oral treatment regimens, either shorter or longer, implemented under programmatic conditions. The 2022 update of the DR-TB treatment guidelines added and prioritized a new 6-month regimen – BPaLM,[2] as a treatment of choice for eligible patients.[4] Patients who cannot be initiated on a BPaLM regimen will be assessed for and be managed with a 9-month shorter oral MDR/RR-TB regimen if eligible. If the patient is ineligible for both shorter regimens, then the patient will be managed with a longer oral MDR/extensively drug-resistant TB (XDR-TB) regimen with appropriate modifications based on the decision of the N/DDR-TBC committee. SHORTER ORAL REGIMENS (9–11 MONTHS) (2) Lzd (4-6) Lfx Cfz Z E H + (5) Lfx Cfz Z E h (6-9) Bdq (4-6) Lfx Cfz Eto Z E H+ (5) Lfx Cfz Z E h (6-9) Bdq LONGER ORAL REGIMENS (18–20 MONTHS) Bdq (6 or 9 months) + Lfx Lzd Cfz Cs (18–20 months). TREATMENT SUCCESS RATES Treatment success rates for TB regimens vary depending on the specific regimen and patient population. BPaLM regimen Although specific treatment success rates for BPaLM are not directly available in the provided data, the World Health Organization recommends this 6-month regimen for MDR-TB patients due to its promising results. It’s considered more effective and shorter than traditional regimens.[5] Shorter oral regimens (9–11 months) A study in Guinea reported a treatment success rate of 71.6% for patients treated with a shorter oral Bedaquiline-containing regimen. This regimen showed a significant reduction in mortality and a higher probability of treatment success compared to injectable regimens.[6] The higher treatment success rate (71.6%) in the Guinea study in the Bedaquiline group was slightly lower than the 74% reported in a South African cohort, but loss to follow-up rate was almost identical in both groups.[6] Hindol Mondal et al., in their study about the efficacy and adverse events of shorter bedaquiline-containing regimens for MDR-TB, mentioned that the overall treatment success rate (defined as cured or treatment completed) was excellent (82.6%) in their study, and this was greater when compared to the previous data by the WHO showing a treatment success rate for MDR-TB of 63% globally.[7] MORTALITY The Bedaquiline regimen was associated with a lower mortality rate (a 38% reduction in all-cause mortality compared to the injectable group).[6] The study also found that women treated with the bedaquiline-containing regimen had a 56% reduction in mortality compared to women in the injectable group.[6] Longer oral regimen (18–20 months) The treatment success rate for longer oral regimens is not explicitly stated in the provided data. However, a large meta-analysis reported a treatment success rate of 74.7% for MDR-TB patients. The longer regimen typically lasts 18–20 months and is used for patients with MDR/XDR-TB. RELAPSE RATE The STREAM trial showed that shorter oral bedaquiline regimens have noninferior efficacy and comparable safety to a longer oral bedaquiline-containing 20 month regimen. However, the trial also showed an increased treatment failure or relapse rates in shorter oral bedaquiline-containing regimens compared to longer oral bedaquiline (20 months) regimen.[8] It is essential to note that treatment outcomes can vary depending on factors such as patient population, drug resistance patterns, and healthcare system. The BPaLM regimen is considered a more effective and shorter treatment option, but its implementation may take time due to factors such as toxicity concerns and availability. SIDE EFFECTS While the Guinea study did not provide an in-depth analysis of side effects, it is essential to note that bedaquiline-containing regimens are generally considered to be better tolerated and easier to administer compared to injectable regimens. Hindol Mondal et al.,[7] in their study, found that patients on shorter oral bedaquiline-containing regimens showed good adherence and tolerance to the treatments and exhibited few side effects. However, they suggested that there is a need for further studies to establish the efficacy of shorter oral bedaquiline-based regimens and explore the serious ADRs in a larger sample population. A comparative study on the side effects of shorter MDR-TB regimens, specifically the bedaquiline-containing regimen versus the injectable regimen, showed promising results. Common side effects associated with bedaquiline include: QT Prolongation: Risk of arrhythmias Nausea and vomiting: Gastrointestinal disturbances Headache: Common adverse effect. Overall, the bedaquiline-containing regimen appears to be a more effective and safer option for MDR-TB treatment, pending the availability of newer regimens like BPaLM. Hence, we can conclude that oral regimens for MDR-TB are generally easier to administer and manage than injectable treatments, enhancing patient compliance. All oral regimens have a more favorable side effect profile compared to regimens containing injectable agents. Oral regimens are said to be more accessible in resource-limited settings as they eliminate the need for specialized equipment and trained personnel required for injectable agents. By avoiding injections and reducing hospitalization needs, all oral regimens improve patient’s overall quality of life and allow them to maintain daily activities. All oral regimens can streamline treatment delivery, making it easier for healthcare systems to manage and monitor patients.