REDUCING DISABILITY

Our strategic goal is to ensure persons affected by leprosy will have prompt and appropriate access to services to prevent and manage leprosy disabilities. To achieve that goal, we are researching, developing, and implementing appropriate treatment regimens to address leprosy-related complications, especially treating leprosy reactions.

Methotrexate as a treatment for ENL

Erythema Nodosum Leprosum (ENL), an inflammatory response in leprosy patients, results in prolonged periods of sickness and disability and if it is not treated can lead to death. The current treatments cause further serious complications and a new treatment option is urgently needed. Methotrexate is used to treat many inflammatory diseases as it suppresses the immune system. TLM Trust India and TLM Nepal are involved in the Methotrexate and Prednisolone Study (MaPs). MaPs - the largest clinical trial on ENL treatment ever conducted, is a multi-centre randomised controlled trial taking place in Ethiopia, Indonesia, India and Nepal.

Funded by the Leprosy Research Initiative, MaPs will test the efficacy of Methotrexate in the management of ENL. Participants in the trial are randomly assigned to receive either the combination of methotrexate and prednisolone or a placebo alongside prednisolone. The study is expected to conclude in 2026, with results anticipated to be published in 2027.

Clofazimine as an ENL treatment

The Extra-Clofazimine Study is a multi-centre clinical trial investigating whether giving extra doses of clofazimine for 6 to 12 months can help reduce the frequency and severity of ENL reactions in patients in India and Bangladesh with smear-positive borderline and lepromatous leprosy. Participants in the study receive either extra clofazimine or placebo vitamins, alongside standard steroid treatment. The study measures outcomes like ENL severity, quality of life, nerve damage, and steroid use to find the best treatment approach. Funded by the Leprosy Research Initiative, the trial began enrolling patients in mid-2023 and aims to finish enrolment by June 2026. The Bombay Leprosy Project leads the India site and TLMI-Bangladesh leads the Bangladesh site.

The scale of NTD-related mental health issues in DR Congo

In DR Congo, 58 percent of men affected by NTDs and 80 percent of women affected by NTDs are screening positive for extreme depressive disorder. TLM Congo has been working with the Liverpool School of Tropical Medicine and Effect Hope to establish the extent of the burden and to develop solutions that are workable and effective. The project has established the scale of the mental health burden through a survey and through photovoice, a process that allows research participants to share their stories through photographs, using their own words to reflect on what is happening within their daily lives. The project's primary intervention was developing peer support groups through collective participation in photovoice. Through this, persons affected have realised that coming together and supporting each other was within their capacity and useful to their wellbeing. As well as support groups, the project has prompted changes at the government level, including the training of local healthcare workers in basic mental health care.

REDUCING DISABILITY

Dovramilast, a potential new treatment for leprosy reactions

Current treatment for leprosy reactions (cortico-steroids and Thalidomide) need to be taken for several months, in some cases for years. Prolonged treatment with these drugs has severe side effects, some of which are permanent. It is therefore essential that we find more effective anti-reaction drugs with fewer side effects.

Dovramilast is a new anti-inflammatory, phosphodiesterase 4 inhibitor, previously known as CC-11050, which is being developed by Medicines Development for Global Health as a potential treatment for leprosy type 2 reaction. It is hoped that it will be a treatment for leprosy reactions with fewer side effects, shorter treatment periods, and less chance of recurrence.

Dovramilast is currently being trialled in participants in Nepal with acute or recurrent leprosy type 2 reactions. The primary known side effects associated with the use of dovramilast include headache, fatigue, diarrhoea and upper respiratory infection. The optimal treatment duration for leprosy type 2 reaction is under investigation.

Profiles of current treatments are:

Prednisolone	Thalidomide
Side effects: diabetes, osteoporosis, hypertension, cataract, peptic ulcers etc. Some patients experience spine fractures due to osteoporosis after using prednisolone for a prolonged period.	Side effects: Sleepiness, constipation, neuropathy, thromboembolism, and toxic effects of congenital birth defects.
Treatment period: A few months to several years in some cases.	Treatment period: A few months to several years in some cases.

Dovramilast has been trialled in both tuberculosis and lupus erythematosus. However, the first trial for the treatment of Type 2 Reaction in leprosy was conducted at The Leprosy Mission Nepal's Anandaban Hospital. This pilot trial at Anandaban Hospital started in 2019 and enrolled 10 male patients. All 10 participants experienced a significant reduction of symptoms within the first 8-10 days, and all 10 cases were resolved within 28 days of treatment. There were minimal side effects and no serious adverse events.

TLM Nepal is currently undertaking a larger trial, which aims to enrol 40 male and female patients to determine whether 12 weeks of dovramilast treatment is safe and effective for the treatment of Type 2 Reaction. The team would also like to explore whether dovramilast could be an effective solution for neuritis in both Type 1 and Type 2 Reactions.

With potentially better outcomes, fewer side effects, and shorter treatment duration, it is hoped that dovramilast will be transformative for reaction patients. Researchers hope these trials will be completed by the early 2030s.