Autoimmune blistering disorders are a group of chronic potentially life threatening disorders characterized by blisters in the skin and or mucous membrane [1]. The incidence among the dermatology outpatient attendees varies between 0.09 to 1.8% [2]. Its prevalence varies from 0.18 to 6.96 cases per 1,00,000 population worldwide [3]. Though corticosteroids are the mainstay of treatment, other modalities like Immunoadsorption techniques, intravenous immunoglobulin’s and monoclonal antibodies have been tried.

Longer and larger doses of steroids are needed to treat these disorders which may lead to a host of adverse effects and even fatality. The commonly practiced Dexamethasone Cyclophosphamide (DCP) Pulse therapy is administered monthly, for more than 3 years. However, the newer drugs (biologicals) have been claimed to be comparatively safer, have shorter duration of therapy, provide faster remission and improved quality of life but at much higher costs.

Aims of the study

To assess the cost of Dexamethasone Cyclophosphamide Pulse therapy.

To assess the cost of low dose Rituximab therapy.

To compare the cost of Dexamethasone Cyclophosphamide Pulse therapy against low dose Rituximab therapy in pemphigus.

We analysed and calculated the cost of DCP for all 3 phases and cost of the low dose Rituximab therapy in the treatment of pemphigus. The prices were considered in the setting of a government tertiary hospital, where most drugs (except Rituximab and cyclophosphamide) and usables are available for free to the patients. However, we need to keep in mind that these drugs or usables were procured by payment from the government (Tables 1-4).

Table 1: List of prices under government setup.

Table 2: List of prices (Drugs and Usables).

Table 3: Comparison of DIRECT COSTS, investigations, medicines in DCP and low dose Rituximab.

Table 4: Comparison of expenditure in full phase of DCP therapy and full course of Rituximab injection in pemphigus.

The parameters taken into account for calculating the cost of therapy were divided as direct costs and indirect costs. They are as follows:

DCP therapy comprises of IV phases of which first, usually is an arbitrary period of 9 pulses followed by II phase of 9 pulses DCP, III phase consists of only oral Cyclophosphamide for 9 months and phase IV is observation for 10 years.

Number of days of hospitalization during each pulse in DCP is 3 days. Total duration of hospital stay: 3 days per pulse × 18pulses=54 days III phase is oral medication, no hospitalization.

DIF is done 3 times in DCP therapy; once for confirmation of diagnosis, 2^nd time during the completion of phase one, and 3^rd time after the completion of phase 2.

DIF is done twice in Rituximab therapy. Initially, for confirmation of the diagnosis and 2^nd time after completion of the 2^nd dose.

A patient needs complete work up of blood parameters before every DCP pulse therapy and at least once in 3 months during phase III. These investigations along with DIF add up to a whopping INR 87,800 for 3 phases of DCP over 27 months.

The indirect cost of DCP therapy is also to be taken into account. These include:

Loss of income of the patient

Loss of income of the attendant

Travelling expenditure of the patient and attendant.

Travel: In this city, the minimum cost of travel by public transport is INR 5. Hence if the patient has at least 1 attender by his side continuously and another shuffling between the house and hospital, that would make 4 trips in a day for 3 days which comes to INR 50. The same in case of Rituximab therapy is INR 30 because of shorter duration of hospital stay.

Usables: For each DCP there is usage of an average of 7 pairs of gloves and one IV cannula and 3 IV drip sets. So it costs about INR 650 for each DCP therapy whereas it costs only INR 300 for Rituximab therapy. Evaluating CD4 counts costs INR 900 and it’s not free for HIV negative patients in our hospital.

Drugs: Though the cost of 1 vial of 500 mg of Rituximab is approximately INR 39,000, the same is provided at a subsidized cost of INR 21,000 for our institution. We have considered the subsidized price in calculating the cost of therapy.

Pulse therapy means administering a drug at supra-pharmacological doses over a short period and then withdrawing it completely till next dose. DCP was introduced in the management of pemphigus vulgaris in the Department of Dermatology, All India Institute of Medical Sciences, New Delhi by Pasricha in 1982. The main objective of using DCP therapy was to achieve faster control of disease activity, reduction in total cumulative dose and to reduce the morbidity due to corticosteroid induced side effects. In the Indian scenario, it is the most commonly used treatment modality for pemphigus unlike in developed countries where it is uncommon [4].

Rituximab is an IgG type chimeric human mouse monoclonal antibody against transmembrane antigen CD20 expressed on B lymphocytes. It induces apoptosis of both circulating as well as tissue based B cells by complement dependent and antibody dependent cellular cytotoxicity. Both lymphoma regimen (four, weekly infusions of 375 mg/m²) and rheumatologic dose (two infusions of one gram each separated by two weeks) have been successfully used to treat autoimmune blistering diseases including pemphigus [5]. Studies have shown that antibody producing B cells in the Pemphigus are not malignant and a single dose as low as 100 mg/m² can deplete B cells [6]. A recent prospective open case series reported that a low dose rituximab regimen consisting of two 500 mg infusions separated by two weeks was effective in pemphigus. This is just 39% of the hematological dose and yet more than 73% of the patients achieved complete remission [6].

Total duration of hospital stay is only two days in Rituximab therapy unlike 54 days in DCP (3 days per pulse × 18pulses=54 days) which is spread over 18 months. In Rituximab group follow up period is 2 years unlike the DCP group where it is about ten years [6-11].

From above analysis it is clear that the total expenditure for a patient to receive 3 phases of DCP over 27 months is about INR 87,800; whereas the total expenditure for two doses of Rituximab therapy is approximately INR 49,594.

The burden of the disease on the family members and medical fraternity is also more in case of DCP therapy when compared to Rituximab therapy.

Low dose Rituximab therapy is more cost effective when compared to 4 phases of DCP. The quality of life is obviously better in low dose Rituximab therapy because of early sustained remission, short duration of hospital stay and no complications of long term steroids. The above advantages also ease the burden of the disease on the family and medical fraternity. If the efficacy and safety profile of Rituximab can be clearly established, then it may be considered as a first line therapy for pemphigus.

We have not compared the efficacy of the drugs nor their adverse effects. We have not compared the change in quality of life of patients treated with DCP and Rituximab therapy.

We have considered the minimum travel charge in our state, but patients may be spending more than what we have calculated while travelling, which will be an additional burden.

In our institution we are getting Rituximab injection 500 mg at a subsidized cost of INR 21,000 while the retail price is approximately INR 40,000.

Larger studies and randomized controlled trials would be valuable to determine the long term safety and efficacy of Rituximab in Indian scenario.

Usables and steroids are free for the patients in a government hospital. Hence, DCP therapy may still remain the poor man’s choice. Since the expenses in DCP are spread over 2 years they provide for a financial cushion, unlike low dose rituximab where patient has to spend entire amount in just 2 weeks.