Indian Journal of Dermatology
  Publication of IADVL, WB
  Official organ of AADV
Indexed with Science Citation Index (E) , Web of Science and PubMed
Users online: 654  
Home About  Editorial Board  Current Issue Archives Online Early Coming Soon Guidelines Subscriptions  e-Alerts    Login  
    Small font sizeDefault font sizeIncrease font size Print this page Email this page

Table of Contents 
Year : 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

Dermatology, Calcutta National Medical College, Kolkata, India

Date of Web Publication16-Apr-2021

Correspondence Address:
Komal Agarwal
Dermatology, Calcutta National Medical College
Login to access the Email id

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ijd.IJD_306_20

Rights and Permissions


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.

Keywords: DCP, dexamethasone cyclophosphamide pulse, pemphigus, rituximab

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

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 2022 Jan 19];66:223. Available from:

   Introduction Top

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 Top

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.

   Results Top

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: Comparative data of patients in both groups

Click here to view

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: Comparison of mean PAAS (cutaneous and mucosal) score and DLQI in the 2 study groups over a period of 9 months

Click here to view

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: (a) Before initiation of Rituximab therapy (b) 3 months After completion of Rituximab therapy

Click here to view
Figure 2: (a) Before initiation of Rituximab therapy (b) 3 months After completion of Rituximab therapy

Click here to view
Figure 3: (a) Before initiation of DCP (b) 9 months After initiation of DCP therapy

Click here to view
Figure 4: (a) Before initiation of DCP (b) 6 months After initiation of DCP therapy (c) 9 months After initiation of DCP therapy

Click here to view

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: Cost breakup of rituximab infusion (RA protocol) and DCP pulse therapy (in INR)

Click here to view

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.

   Discussion Top

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: Improvement of PAAS cutneous and mucosal with DCP and Rituximab

Click here to view

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.

   Conclusions Top

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.

   References Top

Heizmann M, Itin P, Wernli M, Borradori L, Bargetzi MJ. Successful treatment of paraneoplastic pemphigus in follicular NHL with rituximab: Report of a case and review of treatment for paraneoplastic pemphigus in NHL and CLL. Am J Hematol 2001;66:142-4.  Back to cited text no. 1
Kanwar AJ, Tsuruta D, Vinay K, Koga H, Ishii N, Dainichi T, et al. Efficacy and safety of rituximab treatment in Indian pemphigus patients. J Eur Acad Dermatol Venereol 2013;27:1-7.  Back to cited text no. 2
Vinay K, Dogra S. Rituximab in pemphigus: Road covered and challenges ahead. Indian Dermatol Online J 2018;9:367-72.  Back to cited text no. 3
[PUBMED]  [Full text]  
Craythorne EE, Mufti G, DuVivier AW. Rituximab used as a first-line single agent in the treatment of pemphigus vulgaris. J Am Acad Dermatol 2011;65:1064-5.  Back to cited text no. 4
Mascarenhas MF, Hede RV, Shukla P, Nadkarni NS, Rege VL. Pemphigus in Goa. J Indian Med Assoc 1994;92:342–3.  Back to cited text no. 5
Singh R, Pandhi RK. A clinicopathological study of Pemphigus. Indian J Dermatol Venereol Leprol 1973;39:126.  Back to cited text no. 6
[PUBMED]  [Full text]  
Sehgal VN. Pemphigus in India. A note. Indian J Dermatol 1972;18:5–7.  Back to cited text no. 7
Kanwar AJ, Ajith AC, Narang T. Pemphigus in North India. J Cutan Med Surg 2006;10:21-5.  Back to cited text no. 8
Kanwar A, De D. Pemphigus in India. Indian J Dermatol Venereol Leprol 2011;77:439-49.  Back to cited text no. 9
[PUBMED]  [Full text]  
Zambruno G, Borradori L. Rituximab immunotherapy in pemphigus: Therapeutic effects beyond B-cell depletion. J Invest Dermatol 2008;128:2745–7.  Back to cited text no. 10
Anandan V, Jameela WA, Sowmiya R, Kumar MMS, Lavanya P. Rituximab: A magic bullet for pemphigus. J Clin Diagn Res 2017;11:WC01-6.  Back to cited text no. 11
Varala S, Malkud S, Arakkal GK, Siddavaram D. Outcome of pulse therapy in pemphigus: A 10 year study. Clin Dermatol Rev 2018;2:69-73.  Back to cited text no. 12
  [Full text]  
Leshem YA, Hodak E, David M, Anhalt GJ, Mimouni D. Successful treatment of pemphigus with biweekly 1-g infusions of rituximab: A retrospective study of 47 patients. J Am Acad Dermatol 2013;68:404-11.  Back to cited text no. 13
Balighi K, Kamran B, Daneshpazhooh M, Maryam D, Khezri S, Somayeh K, et al. Adjuvant rituximab in the treatment of pemphigus vulgaris: A phase II clinical trial. Int J Dermatol 2013;52:862–7.  Back to cited text no. 14
Heelan K, Al-Mohammedi F, Smith MJ, Knowles S, Lansang P, Walsh S, et al. Durable remission of pemphigus with a fixed-dose rituximab protocol. JAMA Dermatol 2014;150:703–8.  Back to cited text no. 15
Ahmed AR, Shetty S. A comprehensive analysis of treatment outcomes in patients with pemphigus vulgaris treated with rituximab. Autoimmun Rev 2015;14:323–31.  Back to cited text no. 16
Feuring-Buske M, Kneba M, Unterhalt M, Engert A, Gramatzki M, Hiller E, et al. IDEC-C2B8 (Rituximab) anti-CD20 antibody treatment in relapsed advanced-stage follicular lymphomas: Results of a phase-II study of the German Low-Grade Lymphoma Study Group. Ann Hematol 2000;79:493-500.  Back to cited text no. 17
Tony HP, Burmester G, Schulze-Koops H, Grunke M, Henes J, Kotter I, et al. Safety and clinical outcomes of rituximab therapy in patients with different autoimmune diseases: Experience from a national registry (GRAID). Arthritis Res Ther 2011;13:R75.  Back to cited text no. 18
Schmidt E, Goebeler M, Zillikens D. Rituximab in severe pemphigus. Ann N Y Acad Sci 2009;1173:683-91.  Back to cited text no. 19
Herold T, Seiler T, Egensperger R, Trumm C, Bergmann M, Franke D, et al. Progressive multifocal leukoencephalopathy after treatment with rituximab, fludarabine and cyclophosphamide in a patient with chronic lymphocytic leukemia. Leuk Lymphoma 2012;53:169-72.  Back to cited text no. 20
Saoji VA. Premature ovarian failure due to cyclophosphamide: A report of four cases in dermatology practice. Indian J Dermatol Venereol Leprol 2008;74:128-32.  Back to cited text no. 21
[PUBMED]  [Full text]  
Pasricha JS. AIIMS experience. In: Pasricha JS, editor. Pulse Therapy in Pemphigus and Other Diseases 1998. 2nd ed. New Delhi: Pulse Therapy and Pemphigus Foundation; 2000. p. 52-90.  Back to cited text no. 22
Kandan S, Thappa DM. Outcome of dexamethasone-cyclophosphamide pulse therapy in pemphigus: A case series. Indian J Dermatol Venereol Leprol 2009;75:373-8.  Back to cited text no. 23
[PUBMED]  [Full text]  
Mahajan VK, Sharma NL, Sharma RC, Garg G. Twelve-year clinico-therapeutic experience in pemphigus: A retrospective study of 54 cases. Int J Dermatol 2005;44:821-7.  Back to cited text no. 24


  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]

  [Table 1], [Table 2], [Table 3]


Print this article  Email this article
    Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
    Article in PDF (1,764 KB)
    Citation Manager
    Access Statistics
    Reader Comments
    Email Alert *
    Add to My List *
* Registration required (free)  

    Materials and Me...
    Article Figures
    Article Tables

 Article Access Statistics
    PDF Downloaded54    
    Comments [Add]    

Recommend this journal