A Phase Two Randomised Controlled Double Blind Trial of High Dose Intravenous Methylprednisolone and Oral Prednisolone versus Intravenous Normal Saline and Oral Prednisolone in Individuals with Leprosy Type 1 Reactions and/or Nerve Function Impairment

Abstract

BackgroundLeprosy Type 1 reactions are a major cause of nerve damage and the preventable disability that results. Type 1 reactions are treated with oral corticosteroids and there are few data to support the optimal dose and duration of treatment. Type 1 reactions have a Th1 immune profile: cells in cutaneous and neural lesions expressing interferon-γ and interleukin-12. Methylprednisolone has been used in other Th1 mediated diseases such as rheumatoid arthritis in an attempt to switch off the immune response and so we investigated the efficacy of three days of high dose (1 g) intravenous methylprednisolone at the start of prednisolone therapy in leprosy Type 1 reactions and nerve function impairment.ResultsForty-two individuals were randomised to receive methylprednisolone followed by oral prednisolone (n = 20) or oral prednisolone alone (n = 22). There were no significant differences in the rate of adverse events or clinical improvement at the completion of the study. However individuals treated with methylprednisolone were less likely than those treated with prednisolone alone to experience deterioration in sensory function between day 29 and day 113 of the study. The study also demonstrated that 50% of individuals with Type 1 reactions and/or nerve function impairment required additional prednisolone despite treatment with 16 weeks of corticosteroids.ConclusionsThe study lends further support to the use of more prolonged courses of corticosteroid to treat Type 1 reactions and the investigation of risk factors for the recurrence of Type 1 reaction and nerve function impairment during and after a corticosteroid treatment.Trial RegistrationControlled-Trials.comISRCTN31894035

Clofazimine Modulates the Expression of Lipid Metabolism Proteins in Mycobacterium leprae-Infected Macrophages

“…Given the extreme lipophilicity of clofazimine and its activity against many Gram-positive bacteria, clofazimine may interact with the mycolic acid in the M. leprae cell wall that facilitates the exposure of PGN, which in turn activates TLR2-mediated signaling cascades, subsequently decreasing ADRP and increasing HSL [8], [16], [21]. Furthermore, since most lepra reactions, a cell-mediated, delayed-type hypersensitivity immune response, occur during or after MDT [38], [39], the prospect that clofazimine rescues shielded PGN activities, promoting lysosomal fusion and antigen processing, would be a plausible explanation for the trigger of lepra reactions.…”

The effect of systemic corticosteroid therapy on the expression of toll-like receptor 2 and toll-like receptor 4 in the cutaneous lesions of leprosy Type 1 reactions

“…Individuals were randomized to receive intravenous methylprednisolone followed by oral prednisolone or oral prednisolone alone for a total of 112 days. The methods and participants have been described previously 10 …”

Considerations in the design of clinical trials for multibacillary leprosy treatment

“…One of the possible treatments used for ENL is clofazimine, which is bacteriostatic, and may contribute to the smaller reincidence rate observed in some studies [59,60]. Other clinical trials focus on corticosteroid treatment of neuritis or decompressive surgery with impairment the main outcome [61][62][63][64].…”