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:
Participant gender:
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
Details
Lead Sponsor:
Postgraduate Institute of Medical Education and Research