ENL reactions are extreme inflammatory episodes that occur in some leprosy patients with the highest bacterial loads. They can happen before, during, and after MDT treatment and they leave patients feeling extremely unwell, frequently requiring hospital treatment and sometimes leaving them with permanent disability.
Sadly, patients often experience multiple episodes of ENL over an extended period of time. In TLM’s first Research Magazine, Dr Deanna Hagge spoke about the horrors of ENL reactions. She told us,
“When ENL develops, the whole body develops symptoms. Patients have a fever and incredibly inflamed skin lesions all over their body. They can experience severe pain in their skin, nerves, bones, muscles, eyes and/or testicles… At times I have heard men sobbing in pain because their skin is so inflamed that even taking a blood sample is agony.” There is not much research available on this topic, but current estimates suggest that around half of patients who experience an ENL reaction will go on to experience at least one more.
These painful episodes can take months, if not years to subside, which is very hard for a person as they recover in hospital or at home. They can create long-term disability (damage to eyes or nerves) and the current treatments can cause serious side effects, in rare occasions even leading to death. You can read more about that in our first Research Magazine.
If we can find a way to prevent more episodes of ENL, we will have achieved a serious victory. Research that is taking place in Bangladesh could be about to do just that.
Clofazimine is one of the medications used within Multi-Drug Therapy (the treatment for leprosy). As a part of MDT, Clofazimine at a low dose has an anti-bacterial effect, but it can also have an anti-inflammatory effect if given at higher doses. For decades, some clinicians have been using Clofazimine to reduce the seriousness of ENL reactions because it is known to reduce the inflammation.
Although there are many anti-inflammatory medications available, Clofazimine is the only one that has shown any indication of being effective against ENL Many other anti-inflammatory medications are also impractical because using them in combination with prednisolone, the most common treatment for ENL, leads to a serious risk of developing stomach ulcers.
However, there is too little research evidence currently available to support including this use of Clofazimine as a part of global guidelines and, because of this a lack of published evidence, many clinicians believe it would not work.
Our team in Bangladesh are using Leprosy Research Initiative (LRI) and Turing Foundation funding to work with the Bombay Leprosy Project on a research project that could provide the evidence base needed to make this standard practice across the world.
Our team is being led by Principal Investigator, Dr Vivek Pai of the Bombay Leprosy Project. Their current hypothesis is that giving a high dose of Clofazimine for six months to a person who is experiencing their first ENL reaction will lead to less chance of a second episode and, if there is a second episode, it will be less severe. This course of Clofazimine would be provided alongside the existing treatments for ENL.
If their hypothesis proves correct, this treatment would cut both suffering and the rates of disability amongst ENL patients and have a significant impact on the livelihoods and household incomes of patients.
To test the hypothesis, the team will enrol 200 patients who have already experienced ENL across Bombay, Dhaka, and Chittagong for a randomised control trial. This means 100 patients will receive the increased Clofazimine dose and 100 patients will have standard care.
Unfortunately, it is not possible to conduct a double blind trial, where one group receives a placebo, because the increased Clofazimine dosage leads to a discolouration of a patient’s skin, which cannot be replicated by anything else.
The team will start patients with 100mg of Clofazimine three times a day and reduce that over the six-month treatment period. Within MDT treatment, the standard Clofazimine dose is 50mg once a day, so this will be a significant increase in dosage.
The team will monitor the patients through the trial to look for statistically significant differences between the groups in terms of quality of life, increased disability, the amount of steroids they require for treatment, and the time interval before the next episode of ENL, as well as the severity of that episode.
Results from the study will be available from 2025 The project was due to start at the beginning of 2020, but has been delayed by a combination of Covid-19 and supply issues with Clofazimine.
Once the team has a sufficient supply of Clofazimine and once the Covid-19 situation allows, they will be able to commence enrolling patients into the research immediately. The project will require two years for enrolment and two years to follow up the patients, which means results will be available from 2025.
From 2025, the team could have an evidence base that is significant enough to change global guidelines for treating ENL. If that were to happen, it would prevent thousands of avoidable episodes of ENL and transform the lives of the people and families that would have been so painfully affected.
Cover photo credit: Ricardo Franco
