A Study to Evaluate the Efficacy and Safety of Apremilast in Patients of Chronic and Recurrent Erythema Nodosum Leprosum

• Status: Completed
• Trial end date: 2020-06-30
• Target enrollment: 0
• Participant gender: All

Summary

Leprosy is a chronic infectious disease caused by Mycobacterium leprae. The disease manifests with a varied spectrum, ranging from localized tuberculoid leprosy (TT) to generalized lepromatous leprosy (LL) types. The normal course of leprosy is interrupted by troublesome immune reactions, namely lepra reactions. ENL (a type 2 lepra reaction) is an immune-mediated hypersensitivity reaction, presenting as erythematous, tender, papulo-nodules and associated with constitutional symptoms (fever, arthralgias etc). Pro-inflammatory mediators are elevated, especially tumour necrosis factor α (TNF-α), interferon-γ (IFN- γ) and interleukins (IL-2, IL-6, IL-12). LL type and high bacteriological index are considered to be risk factors for ENL. Lesions usually appear after starting MDT, although it may also be presenting feature. Diagnosis is made by characteristic lesions associated with constitutional symptoms and painful nerve thickening. Mild episodes of ENL respond to adequate rest and oral aspirin. Severe episodes necessitate anti-inflammatory drugs like corticosteroids (e.g. Prednisolone) and/or thalidomide. Use of high-dose prednisolone increases risk of steroid toxicity. Thalidomide is category X drug (unsafe in pregnancy), not freely available and has cost-limitations. Clofazimine requires higher doses, takes 4 to 6 weeks to be effective and produces gastrointestinal side-effects and skin discoloration. Minocycline has been tried as an alternative; however the drug itself has been reported to precipitate ENL in some patients. Thus, a safe and effective steroid-sparing agent for ENL remains elusive.

Cyclic adenosine monophosphate (cAMP) is an intracellular signal molecule. Phosphodiesterases (PDEs) catalyse degradation of cAMP leading to its inactivation. Inhibition of PDEs leads to increased intracellular cAMP, which has anti-inflammatory actions. PDE-4 isoenzymes are the predominant cAMP degrading enzymes in most immune cells. Apremilast is an oral phosphodiesterase-4 (PDE-4) inhibitor currently used clinically for the treatment of psoriasis and other chronic inflammatory diseases. The anti-inflammatory effects of apremilast shown in-vitro includes downregulating TNF-α, IFN-γ, IL-2, IL-12 and IL-23. Although apremilast is not yet clinically indicated in ENL, its anti-inflammatory spectrum targeting the same molecules as those implicated in ENL and efficacy seen in other inflammatory conditions warrants its trial in chronic, recurrent ENL patients.

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Postgraduate Institute of Medical Education and Research
• Treatments: Apremilast; Thalidomide

Criteria

Inclusion Criteria:

1. Chronic and recurrent ENL cases of leprosy regardless of age, sex and treatment status with MDT

2. Patients not responded with paracetamol, clofazimine, pentoxifylline, colchicine, methotrexate, azathioprine, TNF inhibitors etc.,

3. Patients who can give valid consent.

4. Willing for monthly follow-up visits for at least 3 months.

Exclusion Criteria:

1. Pregnant and lactating mothers

2. Severe renal dysfunction

3. Patients with HIV, Hepatitis B and Hepatitis C

4. Inability to come for monthly follow up visits for 6 months

5. Those who cannot provide consent for the study

6. Known case of psychiatric disease