Indian Journal of Dermatology
: 2021  |  Volume : 66  |  Issue : 2  |  Page : 223-

A comparative study to evaluate the efficacy and cost of rituximab versus dexamethasone cyclophosphamide pulse in patients of pemphigus vulgaris

Sudip Das, Komal Agarwal, Sonal Singh, Deepika Halder, Sujata Sinha, Abhishek De 
 Dermatology, Calcutta National Medical College, Kolkata, India

Correspondence Address:
Komal Agarwal
Dermatology, Calcutta National Medical College


Introduction: Rituximab is slowly getting recognized as a promising steroid-sparing agent in the treatment of moderate to severe cases of pemphigus vulgaris (PV). We evaluated and compared the effectiveness, safety, and cost of therapy of rituximab versus dexamethasone cyclophosphamide pulse (DCP) in Indian patients with PV. Materials and Methods: It is a retrospective data analysis, from the Immunobullous disease clinic in a tertiary centre of eastern India, of management of PV. In our institute we use either rituximab or DCP for the management of moderate to severe cases of PV, depending on that we retrospectively divided the treated cases of PV in two groups. Patients who were treated with rheumatoid arthritis (RA) protocol of rituximab were considered to be group 1. Patients who were treated with DCP were included in group 2. Response was assessed by pemphigus area, and activity score (PAAS), Dermatology life quality index (DLQI); photographic documentation, and blood parameters were monitored. Results: Both groups showed significant improvement in PAAS and DLQI, the improvement was faster and well sustained in the rituximab group. In terms of safety and development of new vesicles, rituximab had a better profile with only 1 patient having adverse effects and none with new vesicles as compared to DCP (3 had adverse effects and 2 developed new vesicles). Conclusions: Rituximab offers the advantage of early and prolonged remission, lesser adverse effects, better effectiveness, less risk of relapses, faster improvement of PAAS, and DLQI. Though rituximab is an expensive drug, but on evaluating the cost of whole therapy, it was seen that rituximab infusions are actually cheaper compared to DCP pulse. We suggest, rituximab can be used as the first-line of therapy for pemphigus vulgaris in the Indian context.

How to cite this article:
Das S, Agarwal K, Singh S, Halder D, Sinha S, De A. A comparative study to evaluate the efficacy and cost of rituximab versus dexamethasone cyclophosphamide pulse in patients of pemphigus vulgaris.Indian J Dermatol 2021;66:223-223

How to cite this URL:
Das S, Agarwal K, Singh S, Halder D, Sinha S, De A. A comparative study to evaluate the efficacy and cost of rituximab versus dexamethasone cyclophosphamide pulse in patients of pemphigus vulgaris. Indian J Dermatol [serial online] 2021 [cited 2021 Dec 7 ];66:223-223
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Pemphigus vulgaris is an immunobullous disorder that affects the skin and mucosa. It is mediated by circulating antibodies against desmogleins. The treatment of pemphigus vulgaris is quite challenging, systemic corticosteroids in combination with other immunosuppressants has been the mainstay of therapy since time immemorial. The use of long-term corticosteroids in the form of dexamethasone pulse and immunosuppressive therapy may lead to a host of adverse effects and some patients only partially respond to this standard treatment.

To avoid the above adverse effects and achieve better effectiveness and lasting remission, newer treatments are being investigated for pemphigus. The use of biologicals like rituximab has come into the picture. The discovery of rituximab for pemphigus was serendipitous when it was used for non-Hodgkin's lymphoma and lead to the improvement of mucocutaneous lesions of paraneoplastic pemphigus.[1] Rituximab is a chimeric anti-CD20 monoclonal antibody directed against pre-B lymphocytes and mature B lymphocytes. In the Indian scenario, rituximab was first used by Kanwar and colleagues in 2010.[2] In 2018, the US food and drug administration (FDA) approved rituximab for use in adults with pemphigus group of disorders.[3]

Biologicals like rituximab have been claimed to be relatively safer, requiring a shorter duration of therapy, better compliance, faster remission, and improved quality of life but at a much higher cost. At present, Rituximab is being used not only in patients refractory to conventional treatment but also in treatment naïve patients as a first line of drug.[4]

In our institute we use both rituximab and DCP for the management of moderate to severe cases of PV. In this study we have tried to compare the effectiveness, side-effects, and the cost of dexamethasone cyclophosphamide pulse (DCP) therapy with rituximab in PV.

 Materials and Methods

It is a retrospective data analysis conducted in the Dermatology department of a tertiary hospital after obtaining clearance from the institutional ethics committee. Our institute, a tertiary institute of eastern India, the Immunobullous disease clinic maintains the holistic records of patient demography and management. This study was done by retrospective chart analysis of the data of our Immunobullous disease clinic.

The diagnosis of PV is confirmed in our institution with both histopathological examination (HPE) and direct immunofluorescence (DIF). We retrospectively included HPE and DIF confirmed adult (more than 18 years of age) patients of pemphigus who were treated with either DCP or Rituximab in our institute. Patients of pemphigus less than 18 years of age, with preexisting comorbidities like hypertension, diabetes mellitus, heart/kidney/liver dysfunction were excluded from the study.

A complete demographic profile of the patients was noted from medical records including age, sex, occupation, marital status (especially if the family has been completed) as also a family history of pemphigus, menstrual history (in case of females), and duration of illness.

In our institute we use either rituximab or DCP for the management of moderate to severe cases of PV, depending on that we retrospectively divided the treated cases of PV in two groups.

Patients who were treated with rheumatoid arthritis (RA) protocol of rituximab were considered to be group 1 (infusion of 1 gram, 2 doses at a gap of 15 days). Patients who were treated with DCP were included in group 2 (100 mg of dexamethasone in 500 ml 5% dextrose each day for 3 days plus 500 mg of cyclophosphamide on day 2 to be repeated every 28th day along with oral cyclophosphamide 50 mg daily during the pulse-free interval). Remission was taken as the development of no new lesions with healing of all existing lesions with the withdrawal of intermittent steroids, this marked the end of phase 1 of DCP pulse.

Apart from the definitive managements patients were also given Condy's baths, sterile Vaseline gauze dressings, chlorhexidine gargles, antibiotics, and antifungal in individual case basis.

For each patient pemphigus area activity score (PAAS) and Dermatology life quality index (DLQI) at admission were noted.

Follow up examinations were done every 2 weeks during the first month and every month thereafter. It included assessment of skin and mucous membrane, calculation of pemphigus area, and activity score (PAAS), Dermatology life quality index (DLQI), photographic documentation, and blood parameters were monitored.

All patients were routinely administered daily calcium and vitamin D supplements. The patients were followed up for a total of 9 months since the induction of treatment. The number of treatment dropouts and mortality if any were noted. The percentage decrease in score indices at the end of 9 months was calculated from baseline for both the groups. The percentage decrease in both groups was then compared and the P value calculated. P value of less than 0.05 was considered significant.

Along with the above, we analyzed and calculated the cost of DCP for 9 months and the cost of Rituximab therapy (RA protocol) in the treatment of pemphigus.


Twelve treated patients of pemphigus vulgaris were retrospectively enrolled in the study. Out of 12, 8 were males and 4 females (male:female ratio 2:1), all of them had HPE and DIF proven pemphigus vulgaris. The mean age of the patients in the group receiving rituximab infusion was 36 years and the ones in the DCP pulse group were 35.66 years (P-value 0.951). The maximum age of the patient was 55 years and the minimum age being 29 years. The mean duration of illness was 8 months for the rituximab group and 8.3 months for the DCP pulse group [Table 1]. All the patients had cutaneous as well as mucosal involvement. None of the patients had any co-morbidities. The mean PAAS score, both for cutaneous and mucosal involvement were comparable at baseline for both the Rituximab (P = 0.936) and DCP (P = 0.196) group. DLQI at baseline between groups was compared and found to be statistically similar (P = 0.258).{Table 1}

Friedman's ANOVA showed that there was a significant decline of PAAS cutaneous score in both rituximab (P < 0.001) and DCP (P < 0.001) group from baseline at all follow-up visits. When compared to baseline, the PAAS score improved from 1st month onwards, this decrease was consistent over the rest of the visits in both the groups. The reduction in PAAS in the first group beyond 3 months can be attributed to rituximab alone. While assessing mucosal lesions, PAAS-mucosal decreased significantly both in rituximab (P < 0.001) and DCP group (P = 0.003) from baseline till study end. The decrease in mucosal score was faster in the group receiving rituximab compared to DCP pulse. Post-hoc Dunn's test showed that the decrease was significant from 3 months onwards until the study end in both the arms. DLQI also improved after administration of both the agents, significantly from baseline in all follow-up visits [Table 2].{Table 2}

During infusion or pulse therapy and follow up of 9 months, patients were monitored for any adverse effects. The group receiving rituximab infusion did not show any major side effects except infusion reaction in 1 patient which was successfully managed by administering hydrocortisone and restarting infusion after 30 minutes. 3 out of 6 patients receiving DCP pulse reported adverse effects like generalized weakness and cushingoid facies. These side effects were adequately managed [Figure 1],[Figure 2],[Figure 3],[Figure 4].{Figure 1}{Figure 2}{Figure 3}{Figure 4}

None of the patients receiving rituximab infusions relapsed or showed any new lesions during the follow-up period whereas 2 out of 6 patients receiving DCP pulse developed new vesicles during the follow-up period.

During discharge after rituximab infusion or DCP pulse, the patients were started on oral prednisolone 0.5 mg/kg/day which was gradually tapered off according to the response. The group receiving DCP pulse additionally received oral cyclophosphamide 50 mg daily. The oral prednisolone was tapered off and stopped in all 6 patients receiving rituximab by the end of 3 months whereas it had to be continued till 6 months in the DCP pulse group.

The cost of treatment was calculated for rituximab infusion (RA protocol) and DCP pulse for the first 9 months. The cost breakup and the comparison has been shown in [Table 3].{Table 3}

On the calculation of average cost, the total cost of therapy for rituximab infusion was Rs. 77,000 and for the first 9 months of DCP pulse was Rs. 92,700. The difference was approximately Rs. 15,700.


The management of the pemphigus group of disorders is quite challenging because of the relapsing and remitting course, long duration, and the grave effects on the quality of life of the individual. Systemic corticosteroids have been used in the management for years, but long-term use of systemic corticosteroids has its own set of side effects, also they cannot be used in patients with associated comorbidities like diabetes mellitus, hypertension, metabolic syndrome, etc. Biologicals like rituximab offer a good alternative in such scenarios. Rituximab works not only in recalcitrant cases but is also being used as a first-line agent in moderate to severe pemphigus.[4]

There is a dearth of Indian studies that compare the effectiveness of rituximab in pemphigus with conventional dexamethasone cyclophosphamide pulse therapy. The mean age of patients in our study was 35.8 years with male predominance which correlates with few other studies.[5],[6],[7] Mascarenhas MF et al., and Kanwar AJ et al., had reported a female predominance,[5],[8] while Kanwar A in another study found no sex preponderance in pemphigus.[9]

Rituximab has a significant effect in lowering the PAAS from baseline to that at one and three months. The improvement in PAAS and DLQI scores after 3 months of rituximab infusion when oral corticosteroids were tapered off and stopped can be attributed to the effects of rituximab alone in prolonging remission. Rituximab helps to shorten the consolidation phase and the need for oral steroids or other immunomodulators. This long-term remission and rapid response of rituximab has been attributed to various mechanisms like the destruction of autoreactive B and T cells, decrease in anti-desmoglein antibody level, delay in maturation of B cells and the naïve and immature repopulating B cells.[10],[11] no such advantage was seen in the group receiving DCP pulse.

The mucosal lesions responded well to both rituximab infusions as well as DCP pulse, but there was a faster improvement in the case of rituximab [Figure 5].{Figure 5}

There was no effect of age, sex, disease extent, or PAAS on the endpoints of the study and there were no differences in these parameters between the patients of the two groups, thus, making these variables insignificant. Similar observations had been made in previous studies by other authors.[11]

The duration of disease did have a significant impact on the end-point and the chance of relapse. Relapse in pemphigus is defined as the appearance of 3 or more new lesions that do not heal spontaneously within 1 week, or by the extension of established lesions, in a patient who has achieved disease control.[12] Leshem YA et al., had reported a remission rate of 91% after 2nd infusion of rituximab according to RA protocol.[13] None of the patients in the rituximab group relapsed but 2 out of 6 (33.33%) patients in the DCP pulse group relapsed during the follow-up period. Most of the relapses in the pemphigus patients treated with DCP therapy are known to occur during the first 2 years of post-treatment follow-up period.[12]

In our study 1 out of 6 patients (16.6%) receiving rituximab reported immediate adverse effects in the form of fever and urticarial reaction which was adequately managed. No life-threatening side effects were seen. The overall incidence of adverse effects with rituximab as reported in other studies is 1-16% with infusion reactions and reactivation of infections being quite common.[14],[15],[16] The most frequent infusion-related side effects include fever and rigor.[17] Others being flu-like symptoms, nausea, vomiting, abdominal pain, and hypotension. Treatment-related side effects occur most frequently at the first antibody infusion (65%) and less often during the second (15%), third (5%), and fourth (5%) infusions.[18] Many of these reactions are mild and only require a reduction in the infusion rate. Infections are the major cause of death and are mainly bacterial, opportunistic infections are infrequent.[17] Bacterial sepsis, bacterial pneumonia, pyelonephritis, Pneumocystis carinii pneumonia, bacterial arthritis, cytomegalovirus gastritis, Listeria monocytogenes sepsis, varicella-zoster infection, and cutaneous Mycobacterium chelonae infection are some of the serious infections reported in pemphigus patients receiving rituximab.[19] Rare side effects like progressive multifocal leukoencephalopathy (PML), a JC virus infection of the brain has been reported in patients receiving rituximab, but such reactivation has not been reported in any patient of pemphigus receiving rituximab.[20] In spite of all the above side effects listed, they are extremely rare in patients of pemphigus receiving rituximab infusion as compared to the adverse effects of long-term corticosteroids which are frequently seen.

On the contrary, 3 out of 6 patients (50%) receiving DCP pulse reported side effects like generalized weakness, oligomenorrhoea, and cushingoid facies. Most of the side effects of DCP pulse are seen in phase I of pulse therapy.[12] High incidence of generalized weakness especially within 7 days of DCP infusion was reported by Varala et al.[12] Gonadal toxicity is a well-known side effect of cyclophosphamide.[21] Pasricha noted amenorrhoea in 50% women who received DCP for pemphigus.[22] Similar observations were made by Kandan et al. and Mahajan et al.[23],[24]

Rituximab, in spite of having advantages like better compliance, fewer infusions, better effectiveness, faster remission, lesser side effects has still not been able to replace DCP pulse therapy completely because of the assumed high cost of rituximab. We analyzed and compared the total cost of rituximab therapy (RA protocol) with 9 months of DCP pulse therapy. The cost of DCP pulse therapy was approximately 17,000 INR more than rituximab therapy. Even though rituximab as a drug is expensive, but from the above analysis it is clear that if other costs like investigations, hospital charges, wages lost, etc., are considered the total cost of DCP therapy is much higher than that of rituximab. The only pitfall being, the major chunk of the expenditure in case of rituximab has to be borne at a time.

Thus, above factors contribute to better compliance, less expenditure on hospital admissions, traveling expenses, and loss of daily wages while using rituximab. The long-term DCP therapy does have an additional psychological burden on the patient and family member. On comparing the risk-benefit ratio and the cost, rituximab does weigh above DCP pulse therapy for pemphigus.


In our analysis rituximab was more efficacious than DCP pulse therapy for cutaneous lesions of pemphigus vulgaris. Even though the improvement in mucosal lesions was the same with rituximab and DCP at the end of the study period, rituximab did induce faster remission. Rituximab offers the advantage of early and prolonged remission, lesser adverse effects, better effectiveness, less risk of relapses, lower fatality, faster improvement of PAAS, and DLQI. It is effective as a first-line drug as well as for cases recalcitrant to standard DCP pulse therapy. It offers better patient compliance in terms of lesser days of hospital stay, less loss of daily wages, fewer infusions, low risk of side effects, and shorter duration of follow up. Its only limitation in a developing country like India was its cost.

Even though rituximab is an expensive drug as it demands a one-time payment to procure the drug, but if the cost of whole therapy is taken into account, it was seen that rituximab infusions are actually cheaper compared to DCP pulse. On the basis of the above analysis, rituximab can be considered as the first-line of therapy for pemphigus vulgaris in the Indian context.


The limitation of our study was that the analysis was retrospective and the sample size was small. Indirect immunofluorescence could not be done because of a lack of set-up for the same at our hospital. Further large-scale prospective study with serological tests may provide better insights.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.


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