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There is paucity of data on infusion related hypersensitivity reactions (IRHR) pattern of bio-similar rituximab in B-cell lymphoma patients. As bio-similar molecules are independently developed monoclonal antibodies, they are likely to differ in immunogenicity and therefore, the hypersensitivity data of the innovator rituximab may not be directly applicable to patients treated with the biosimilar rituximab molecule. We analysed our data of 256 patients of B cell lymphoid neoplasm who received bio-similar rituximab (Reditux) based chemo-immunotherapy for their treatment. Total 56/256 (21.8%) patients had ≥ grade II IRHR with first dose of rituximab. Grade II reactions were seen in 32/256 (12.5%) cases, grade III and grade IV reactions were seen in 21/256 (8.2%) and 3/256 (1.2%) cases, respectively. Rituximab was withdrawn from all further therapy in only 2 patients due to grade IV IRHR after attempting re-challenge of the drug under intensive monitoring. There was no difference in complete response rates in patients with or without IRHR during their first rituximab infusion. The IRHRs with bio-similar rituximab noted in our study were comparable with the previously published reactions associated with the original rituximab.

Diffuse large B cell lymphoma (DLBCL) is the most common form of non-Hodgkin lymphoma among adults, although it also affects the young and the elderly. DLBCL is treated with a chimeric monoclonal antibody against CD20, a B cell surface protein, named rituximab, in combination with a multidrug chemotherapeutic regimen. However, owing to its high cost, rituximab cannot be afforded by patients in developing or underdeveloped countries. In such cases, biosimilars of rituximab have been used instead of rituximab, with equivalent efficacy. In this single center, retrospective, observational study, we have compared patient outcomes such complete response (CR), partial response (PR), and overall response rate (ORR) in a cohort of 152 patients in an Indian hospital, who were treated either with innovator rituximab or Reditux, a biosimilar. We observed that the ORRs of both groups (88% in innnovator group and 82% in biosimilar group) were comparable. There was no statistically significant difference between the two groups in terms of CR (p = 0.353), PR (p = 0.42), ORR (p = 0.23), unfavorable responses, and stable or progressive disease (p = 0.42). The number of patients who died due to complications were few, and there was no significant difference between the two groups. The differences in the 3-year event-free survival and overall survival were not statistically significant. Biosimilar rituximab can suitably and safely replace the innovator rituximab for treatment of diffuse large B cell lymphoma.

In order to demonstrate physicochemical comparability of a recombinant protein medicament as a drug substance (Active Pharmaceutical Ingredient or API), such as Rituximab, one must first choose suitable orthogonal analytical methods that selectively provide information regarding the identity and heterogeneity of the molecule. The application of these methods in the investigation of process-derived variability of the reference molecule can yield valuable information to establish comparability criteria. This could become the basis to determine the critical physicochemical attributes that should be verified by relevant in-process controls and batch release criteria. In this paper we show the determination and analysis of relevant attributes from two different proposed biosimilars. We show differences in Reditux proposed Rituximab biosimilar, mainly in charge heterogeneity patterns, whereas no major differences were found for Kikuzubam as related to the Mabthera reference batches. The detected differences are...

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Rituximab (MabThera™, Roche) is a chimeric IgG1 monoclonal antibody targeting the CD20 surface antigen on normal and neoplastic B cells. It revolutionized the treatment of non-Hodgkin’s lymphoma with superior progression-free and overall survival. However, its prohibitively high cost makes it inaccessible to majority of patients in developing countries. Reditux™ (Dr. Reddy’s Laboratories, India), a biosimilar, was introduced in India in 2007 at nearly half the price of the innovator. However, there is a dearth of data regarding the pharmacokinetics and efficacy of Reditux™. Twenty-one patients of diffuse large B-cell lymphoma on R-CHOP regimen were enrolled for the study. Reditux™ was administered as a slow intravenous infusion at a dose of 375 mg/m2 on day 1 of a 21-day cycle. Pharmacokinetic sampling was performed at pre-dose, post-infusion, 24, 48 h, 7 and 21 days. Rituximab levels were estimated by ELISA. Population pharmacokinetics was performed using NONMEM. In addition, B-cell count was determined at baseline and days 3 and 21 of the first cycle. Survival analysis was performed using Kaplan–Meier plots. The volume of distribution of central compartment and clearance of Reditux™ were estimated at 0.95 L and 5.98 mL/h, respectively. No covariate effects were seen. B-cell count was completely depleted by day 3 and remained so on day 21. Overall survival was 84.6 % at a median follow-up of 36 months. The pharmacokinetic profile and B-cell response to Reditux™ are comparable with those reported for MabThera™. Thus, MabThera™ can be substituted with Reditux™ for the treatment of B-cell lymphomas.

Rituximab (anti-CD20 monoclonal antibody) has shown to improve symptoms in rheumatoid arthritis (RA) patients with inadequate response to conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs). An anti-CD20 monoclonal antibody (Reditux™) developed by Dr. Reddy’s Laboratories, India, is currently approved for use both in rheumatology and oncology patients. This retrospective report evaluates the efficacy and safety data from the real-world use of Reditux™ over a 6-month period in Indian patients with RA. All consecutive moderate to severe RA patients who failed therapy with at least two DMARDs including methotrexate (MTX) for 6 months, TNFα inhibitor naive, and willing to take Reditux™ were included. They were prescribed two doses of 1 g Reditux™, at least 15 days apart, with continued stable doses of methotrexate. Efficacy and safety after 24 weeks relative to baseline was assessed using various health assessment variables. A total of 39 patients (mean age of 46 years; 67.5 % females) treated with Reditux™ were evaluated. Statistically significant differences were observed in mean changes of DAS28-CRP, DAS28-ESR, SDAI, HAQ and Patient Global Assessment scores from baseline to 24 weeks (p

Background: Rituximab (Mabthera™) have been in use in India since 2000. A biosimilar molecule of rituximab (Reditux™) was approved in India in 2007. This retrospective audit was done to compare the efficacy and safety of Mabthera™ with Reditux™. Materials and Methods: We reviewed the charts of 223 adult diffuse large B-cell lymphoma patients who had received cyclophosphamide, doxorubicin, vincristine and prednisolone with rituximab chemotherapy. Tumor recurrence, survival and toxicities experienced during chemotherapy were obtained from the patient charts. The survival analysis was restricted to patients who received at least 4 cycles of the same brand. Results: Of the 223 patients evaluated, 101 received Mabthera™, 72 received Reditux™. There were no differences in the infusional reaction rates, grades 3 and 4 neutropenia and oral mucositis between the two brands. Complete-remission (CR) rates were similar with Mabthera™ and Reditux™ (75% and 82%, respectively; P = 0.294). The progression free survival (PFS) rate at 5 years were 72% in Mabthera™ and 81% in Reditux™ (P = 0.382). The overall survival (OS) at 5 years were comparable in the two groups (66% in Mabthera™ and 76% in Reditux™; P = 0.264). Conclusion: We observed no significant differences in the toxicity, tumor response rates, PFS and OS between the two available brands of rituximab.

Background: Rituximab is a chimeric IgG1 monoclonal antibody targeting the CD20 surface antigen on normal and neoplastic B cells. Its use in combination with chemotherapy in CD20 positive B cell lymphomas has translated into better progression free and disease free survival making its incorporation, a standard of care in treatment of these lymphomas. However, the benefits of this important molecule may not have been available to a majority of patient in the developing countries but for the emergence of biosimilars in the market. The lack of defined regulatory norms in approving biosimilars for patient care has left some doubts regarding their true efficacy in comparison to the innovator MabThera® (Roche). Although our clinical experience suggests comparable efficacy and safety for the biosimilar, we embarked on a formal pharmacokinetic study of the biosimilar, Reditux®, used in combination with standard CHOP or CHOP like regimen in patients with diffuse large B cell lymphoma planned for chemo-immunotherapy. We present our data on twenty-one prospectively treated patients and compared it with the published data on MabThera®. Methods: This was a prospective, single centre pharmacokinetic study conducted between Nov 2011 and June 2013. Patients diagnosed with DLBCL, and treated with Reditux® in combination with chemotherapy, were enrolled into the study. All patients received six cycles of R-CHOP, wherein they received 375mg/m2 Reditux as a graded infusion of 50mg, 100mg and maximum 200mg during the first, second and third hour respectively on day 1 of first cycle. The chemotherapy consisted of standard CHOP including cyclophosphamide 750 mg/m2, doxorubicin 50 mg/m2 and vincristine 1.4 mg/m2 (for a maximum single dose of 2 mg), administered intravenously on day 1 after Rituximab infusion, along with 100 mg oral prednisone for 5 days from first day. Serial blood sampling was done during the first cycle of R-CHOP at pre-dose, immediately post infusion and thereafter at 24, 48, 144 hours post infusion with a last sample collected on day 21. The plasma level of rituximab was determined by ELISA (Life Technologies, USA) with a sensitivity of 50 ng/mL. Rituximab AUC and other pharmacokinetic parameters were calculated from the observed concentrations at each time point using WinNonlin® version 6.3. The peripheral blood B-cell count was done on day 3 and day 21 of chemoimmunotherapy. The absolute B cell percentage was calculated by flow-cytometry using CD45, CD19 and CD20. Influence of covariates on AUC of Reditux was analyzed by linear regression. Results : A total of 21 patients were enrolled into the study including 18 males and 3 females. The median age was 50 years in the Reditux® group (range 24-70). Four patients were above 60. Majority (n=12) had Stage 4 disease. The pharmacokinetic parameters described in the table were comparable with the pharmacokinetic profile of MabThera® from published literature. High inter patient variability in pharmacokinetics was observed (CV=88%). Age and gender did not influence pharmacokinetics of the biosimilar though the numbers are few to derive firm conclusions. The median B cell count on day 3 and day 21 of first cycle was 1.75 ± 0.27 and 5.56 ± 1.24 cells/µl respectively. Of the 21 patients, four were lost to follow up while 2 patients had progressive disease and died. At a median follow of 19 months 70.3% of patients from the Reditux® group were progression free. There was no untoward immediate or late toxicity attributable to Reditux® on follow up. Conclusions: Reditux® has similar pharmacokinetic profile as MabThera®. The B-cell kinetics following Reditux® administration are similar to that reported for MabThera®. This study gives further credence to Reditux® as a suitable alternative to MabThera®in the treatment of CD20 positive B cell lymphomas. | PK parameter (mean ± SD) | Reditux® (N=21) | MabThera® (published literature) | | ------------------------ | ---------------------- | ---------------------------------------- | | AUC (0-t) hr* µg / mL | 54,236 ± 47,555 | - | | C max (µg / mL ) | 555.74 ± 141.46 | 408 | | Vd ( L) | 1.3 ± 0.64 | 2.7 | | CL (l/day) | 0.15 ± 0.16 | 0.14 | | Half life (days ) | 10.9 ± 8.6 | 22 | | MRT last (days) | 2.78 ± 3.08 | - | Table: Pharmacokinetic parameters of Reditux® and Mabthera® Vd=Volume of distribution, CL=Clearance, MRT=Mean Residence Time Disclosures No relevant conflicts of interest to declare.