A multicenter study of recombinant interferon-alpha2b in the treatment of multibacillary leprosy

International Journal of Leprosy and Other Mycobacterial Diseases, Dec 1997 by Ganapati, R, Pai, V V, Banerji, Udai, Thomas, Jaykar, Saha, B

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A Multicenter Study of Recombinant Interferon-Alpha2b in the Treatment of Multibacillary Leprosy

TO THE EDITOR:

Lepromatous leprosy has well-documented deficiencies in the macrophage regulation system (9). The role of cytokines, such as gamma-interferon (IFN-gamma, interleukin 2, tumor necrosis factor in macrophage stimulation (8), natural killer (NK) cell activity and antibody-dependent cellmediated cytotoxicity (ADCC) (3), have been described. Combination chemotherapy utilizing drugs like dapsone, rifampin, and clofazimine (6) and newer groups of drugs such as macrolides (7) and quinolones (Il) have been shown to be effective. The rate of fall of the bacterial index (BI) is about 1 log per year. The search is now on to try to achieve a higher cell kill and to clear the dead bacilli faster.

The treatment of patients having lepromatous leprosy with local IFN-gamama has been tried before (2, 5,12). They are shown to have rapid bacillary clearance and increased H^sub 2^0^sub 2^ release by macrophages when IFN-gamma was injected locally (13). IFN-gammahas a poor muscle and skin absorption along with a short half-life of 25-30 min (4).

Alpha-interferon (IFN-alpha) has been used extensively to treat malignancies (') and viral infections (10). The role of IFN-alpha on NK cell activity and ADCC has been documented in vitro (3). The clinical efficacy of IFN-alpha in leprosy has not been evaluated before.

MATERIALS AND METHODS

Forty patients with lepromatous leprosy were randomized to the multidrug therapy (MDT) arm or MDT-interferon (MDTI) arm of our study. The treatment on the MDT arm consisted of dapsone 100 mg and clofazimine 50 mg daily along with rifampin 600 mg and clofazimine 300 mg monthly, the duration of treatment being 24 months. The MDTI arm consisted of the above treatment along with alpha-interferon 2b (IFN-alpha2b) at a dose of 3 million units subcutaneously twice a week for 6 weeks. The clinical features, BI, histology and lepromin reactivity were documented at baseline and at 3 months. The clinical features will be followed up monthly for 24 months and yearly thereafter. While the BI was read as it normally is, the histology was scored according to a predetermined histological scoring system.

Statistical methods. The Mann-Whitney U test for unpaired ordinal variables and an unpaired t test for continuous variables were used.

RESULTS

We were able to evaluate the histology for 30 patients (20 on the MDTI arm and 10 on the MDT arm). There were 37 patients for whom we were able to evaluate the BI (19 on the MDTI arm and 18 on the MDT arm). The baseline median histopathological score was 3 for both the MDTI and the MDT arms. The mean BIs also were similar, 3 and 3.1 for the MDTI and MDT arms, respectively. The mean fall in the BI was 1.526 and 0.547 for the MDTI and MDT arms, respectively, the difference of 0.98 (95%CI 0.45-1.50) being significant (p = 0.001) (The Table, The Figure). The mean fall in the histopathology score was 0.85 and 0.2 in the MDTI and MDT arms, respectively, this too being significant (p = 0.029).

Lepromin reactivity was negative in all patients at baseline and continued to be so after 3 months.

Clinical features studied included infiltration and erythema, the differences in preand post-treatment scores were significant, p = 0.0009 and p = 0.0001, respectively.

There was one type 1 reaction on the MDT arm and one type 2 reaction on the MDTI arm. Apart from malaise and mild fever following the injections there was no major side effect attributable to IFN-alpha.

DISCUSSION

The bacterial cell kill after chemotherapy is probably effective, but dead bacilli remaining in the soft tissue often contribute to disease morbidity. The fall in the BI is one of the modes of following up the load of dead bacteria. Cytokines play a role in the activation of macrophages which is important in the removal of bacteria and cells from the dermis. The addition of a short course of IFN-alpha to the MDT seems to have significantly enhanced the fall in the BI at an early stage of the treatment itself.

The baseline histology in all of the patients revealed a clear subepidermal layer and foam cells. The patients who were given IFN-alpha along with the MDT had a more rapid clearance of foam cells which could, again, signify an enhanced cell-mediated clearing of the dead cells.

Lepromin testing is a measure of the cellmediated activity manifested by the body; this did not seem to be altered by the addition of IFN-alpha to the MDT during the period of the study.