Biosimilars in pemphigus vulgaris.

Sir,

Pemphigus is a chronic autoimmune blistering disease affecting both the skin and mucous membranes. Until recently, steroids were the mainstay of therapy. Although undoubtedly effective, the side-effects of this drug made a search for alternative or supplementary therapies mandatory. Pulse therapy with steroids,[1] antimetabolites and intravenous immune globulins[2] were some of the therapeutic alternatives introduced in recent years.

Rituximab, a biological, was also given to certain refractory patients with good results. It is a chimeric monoclonal antibody against the protein CD20, a B-cell specific antigen and is given in a dose of 375 mg/m2. Various treatment protocols are advised.[3] However, the cost of the original rituximab formulation has made it unaffordable to the vast majority of Indian patients. The advent of the concept of “biosimilars” has alleviated this problem to a certain extent.[4]

“A biosimilar is a biological product that is highly similar to a US-licensed reference biological product with no clinically meaningful differences between the biological product and the reference product”.[5] They are similar but not identical unlike generic molecules. Hence they can be used without concern to patent issues. With time, as patency of original product will expire, cheaper biosimilars will be increasingly used and this will obviously decrease the costs for the patient.

We gave rituximab cycles to five female patients with an average age 37.8 years and average duration of the disease 34.8 months. All these patients were shifted from conventional therapy to rituximab either due to failure of conventional therapy or side effects.

Therapy was given in an intensive care setup with proper monitoring. Patients were evaluated periodically by a hemato oncologist for serious side-effects.

Two patients received one cycle of rituximab according to lymphoma protocol (4 doses of 375 mg/m2 at weekly intervals for 4 weeks) and other three patients received low dose rituximab[6] (2 doses of 375 mg/m2 at 2-weekly intervals), as they were not affording. After rituximab, two of these patients were maintained on oral cyclophosphamide 50 mg, while the other three were started on oral mycophenolate mofetil for a period of 6 months to 1 year. The details of the individual patients are shown in the accompanying table [Table 1].

Table 1

Details of the patients recieving Rituximab

It can be seen that all patients who received 4 doses showed complete resolution as defined by the criteria of the International Pemphigus committee.[7] Anti-desmoglein levels were done in one patient, which thus showed decreased levels over a period of 8 months. The skin lesions started healing after the first cycle itself and systemic problems such as pain, malaise and fever also disappeared. All the lesions healed at the end of therapy and have not relapsed. The longest follow-up has been of 2 years. All the patients have achieved complete remission and time to disease control was three to 5 months. This has been associated with a significant improvement of the quality-of-life in these patients. In fact, patient number 2 is now pregnant (7 MA) and the pregnancy is proceeding uneventfully with no relapse of skin lesions.

As far as side-effects are concerned, several have mentioned in the literature,[7] including infusion reactions, opportunistic infections and possible induction of malignancy. In our patients, however, except for mild transfusion associated reactions, the treatment was well-tolerated. These did not necessitate cessation of the drug.

Our study had a few limitations. Our sample size was small. We had no control group where patients were given standard therapy. We did not standardize the dose. Moreover, our patients were only those who could afford the cost of therapy (each cycle of the biosimilar costs Rs. 65,000/). Our follow-up period is not adequate enough to conclude with confidence that rituximab can induce long-term remissions.

We would like to conclude that biosimilars of rituximab could be the future in pemphigus vulgaris, especially in a country like India, instead of biologicals. The latter cannot be given to the overwhelming majority of patients because of financial constraints.