Patients In Rituximab Group Research Articles

Single-Dose Rituximab Plus Glucocorticoid Versus Cyclophosphamide Plus Glucocorticoid in Patients with Newly Diagnosed Acquired Hemophilia a: A Multicenter, Open-Label, Randomized Clinical Trial

Introduction Cyclophosphamide plus glucocorticoid is a first-line immunosuppressive therapy for acquired hemophilia A (AHA), a serious bleeding disorder, but brings risks of myelosuppression, secondary tumor, and reproductive toxicity. Rituximab plus glucocorticoid therapy shows comparable efficacy but lacks results from randomized controlled trials. We aimed to establish whether the single-dose rituximab regimen was non-inferior to the cyclophosphamide regimen. Methods This study was the first noninferiority, multicenter, open-label, randomized controlled clinical trial comparing these two combination therapies in AHA patients (ClinicalTrails.gov number, NCT03384277). Adult patients (18-80 years) with newly diagnosed AHA from five centers in China were randomly assigned 1:1 to receive glucocorticoid (methylprednisolone 0.8 mg/kg per day for the first 3 weeks and then tapered) plus single-dose rituximab (375 mg/m 2) or plus cyclophosphamide (2 mg/kg per day until inhibitor becomes negative, for a maximum of 5 weeks). The primary outcome was complete remission (CR, defined as FVIII activity ≥ 50 IU/dL, FVIII inhibitor undetectable, immunosuppression tapered and no bleeding for 24 hours without bypassing agents) rate measured within 8 weeks. The noninferiority margin was an absolute difference of 20%. The secondary outcomes included partial remission (PR) rate, time to PR, time to CR, time for inhibitor titer to decrease by 50% of baseline, relapse rate, time to relapse and so on. Safety was assessed in all patients. Results Between December 29, 2017 and June 9, 2022, 67 patients were screened, of whom 63 (33 female and 30 male) were assigned: 31 to single-dose rituximab group and 32 to cyclophosphamide group. The baseline characteristics of these patients were balanced between the single-dose rituximab group and cyclophosphamide group. Twenty-four (77.4%) patients in the rituximab group and twenty-two (68.8%) patients in the cyclophosphamide group achieved CR, which showed the noninferiority of the single-dose rituximab-based regimen (absolute difference=-8.67%, lower limit of the 95% confidence interval=-13.11%; P noninferiority=0.005). PR was observed in 25 (80.6%) of 31 patients in the single-dose rituximab group and 26 (81.3%) of 32 patients in the cyclophosphamide group (P=0.95). The median time to PR was similar between two groups (23.0 days for rituximab group vs. 25.5 days for cyclophosphamide group, P=0.47). The median time to CR was 8 days shorter in the single-dose rituximab group than in the cyclophosphamide group, but with no statistically significant difference (28.0 days vs. 36.0 days, P=0.41). The median time for inhibitor titer to decrease by 50% of baseline also showed a shorter trend in the single-dose rituximab plus glucocorticoid group (8.0 days vs. 11.0 days, P=0.39). Subgroup analysis showed patients with high FVIII inhibitor titer (>20 BU/ml) were less likely and slower to achieve both CR and PR. The percentage of patients who experienced treatment-related adverse events (TRAEs) or grade 3 or 4 TRAEs were comparable between the rituximab and cyclophosphamide groups (58.1% vs. 37.5%, P=0.10 and 12.9% vs. 6.3%, P=0.43 respectively). Conclusion Single-dose rituximab plus glucocorticoid regimen showed similar efficacy and safety in this trial, without a reported risk of secondary malignancies or reproductive toxicity seen in cyclophosphamide, it might be recommended as a first-line therapy for AHA, especially in China where there is a young age trend in AHA patients.

Clinical Efficiency of Rituximab Combined with Autologous Hematopoietic Blood Stem Cell Transplantation for Treatment of CD20+ B non.Hodgkin Lymphoma

From January 2005 to December 2013, 83 patients with refractory/recurrent CD20+ B.NHL who were treated with auto.HSCT in our department were enrolled. The patients were divided into 2 groups: 57 patients in Rituximab group, and 26 patients in control group(without Rituximab). All the patients received chemotherapy and auto.HSCT. For the patients in treatment group, Tituximab was used before transplantation of the stem cells, and for some patients Rituximab was used after transplantation. For the patients in control group, the induction, enhancement and transplantation were the same as those in treatment group. The clinical efficiency of the patients in treatment group according to the time and frequency of R was analyzed in subgroups and compared with the control group. The deadline of follow.up was April 30 2014. All the patient achieved complete response. The median follow.up time was 39 months. Both the two groups collected peripheral blood stem cells successfully, and had no difference in hematopoietic reconstitution time. Three patients in treatment group and six patients in control group relapsed and the three year overall survival and EFS in treatment group was significantly higher than that in control group, that is（93.0% vs 73.1%, P=0.037） and （89.5% vs 65.4%, P=0.034）, respectively. Subgroup analysis showed that: compared with the treatment group in which using R in the whole courses(before and after transplantation, and collection of stem cells) was superior to the control group in both OS and EFS, with the OS 97% vs 87.5% (P>0.05) and EFS 97% vs 76.2% (P=0.05) respectively. While stratified by the different courses of rituximab, the OS was 88.9% (1-2 courses, 9 cases), 93.1% (3-4 courses, 29 cases), 94.7%(more than 5 courses,19 cases), and EFS was 77.8%, 89.7% and 94.7%, respectively. For the patients with refractory/recurrent CD20+ B.NHL, the combination of R and inducing chemotheraphy, purify in body before transplantation, as well as continue with R after auto.HSCT could obviously improve the OS and EFS of patients. For the patients who with R before and after transplantation, their EFS is better than the patients with R before transplantation only.

Clinical features and prognosis of pneumocystis pneumonia in patients treated with rituximab for autoimmune diseases

Objective: To determine the clinical features and outcomes of pneumocystic pneumonia (PCP) in patients treated with rituximab for autoimmune diseases. Methods: PCP patients with autoimmune diseases as underlying diseases from January 2009 to April 2019 in Peking University First Hospital (male 67 cases, female 35 cases, age 17-79) were retrospectively reviewed. Patients were grouped as rituximab group and non-rituximab group based on the fact if they were treated with rituximab before the onset of PCP. Demographic data, clinical features, and outcomes of the two groups were analyzed. Results: There were 102 cases altogether, and 7 patients were treated with rituximab before the onset of PCP. Patients in rituximab group were relatively younger than that in non-rituximab group [(32.0±18.7) vs (52.4±14.9) years, P=0.010]. Patients in rituximab group had more CD3(+), CD4(+), CD8(+)T lymphocytes in peripheral blood samples than that in non-rituximab group [(1 306±596) vs (546±439)/μl, (674±401) vs (243±232)/μl, (616±249) vs (282±256)/μl, respectively, all P<0.01]. However, the B lymphocyte count and plasma level of IgG and IgM were significantly lower in rituximab group than that in non-rituximab group [0 (0, 0.2) vs 72 (50.0, 124.4)/μl, 4.0 (2.6, 5.8) vs 9.4 (5.3, 12.0) g/L, 0.3 (0.2, 1.0) vs 1.1 (0.6, 1.8) g/L, respectively, all P<0.05]. The incidence of Cytomegalovirus (CMV) pneumonia was significantly lower in rituximab group (0/7 and 57/95, P=0.007). Other demographic data, the use of corticosteroids, the incidence of severe PCP, mechanical ventilation, intubation, pneumothorax and mediastinal emphysema complications, as well as hospital mortality and length of stay in hospital in the two groups were comparable. Conclusions: In patients treated with rituximab for autoimmune diseases, the number of B lymphocytes in peripheral blood and the plasma level of immunoglobulins but not CD3(+), CD4(+), and CD8(+)T lymphocyte counts may play an important role in the pathogenesis of PCP. These patients are not vulnerable to be complicated with CMV pneumonia.

Similar Efficacy and Safety of CT-P10 and Reference Rituximab in Patients with Advanced Stage Follicular Lymphoma: Updated Phase III Study Results

Background: CT-P10 is an approved biosimilar to the innovator rituximab (RTX) from many countries including European Union based in part on the pharmacokinetics (PK) equivalence and comparable efficacy in patients with previously untreated advanced follicular lymphoma (FL) when treated with rituximab plus cyclophosphamide, vincristine and prednisone (R-CVP) as an induction therapy (Coiffier B et al. ASH 2016; Kim WS et al. ASCO 2017).Objective: We report here the updated efficacy outcomes including progression free survival (PFS), duration of response, overall survival (OS), as well as updated safety profile of CT-P10 compared to RTX in advanced FL patients with median follow-up duration of 23 months including the Maintenance Period with rituximab monotherapy.Methods: These results were derived from an ongoing randomized and double-blind study in patients with previously untreated advanced FL (NCT02162771). A total of 140 patients were randomized in a 1:1 ratio and 124 patients completed 8 cycles of R-CVP induction therapy. One-hundred twenty two patients (62 patients in CT-P10 group and 60 patients in RTX group), who showed response during the Induction Period, entered the Maintenance Period where a total of 12 cycles of rituximab monotherapy was to be administered every 2 months. The study was planned to continue until death or up to 3 years from the randomized date of the last patient. Kaplan Meier (KM) method was used to estimate PFS, duration of response, and OS.Results: Both groups had similar baseline characteristics; overall median age of 58 years, 55% female, 57% with FLIPI score ≥3, 100% with Stage III/IV, 18% with bulky disease (≥7cm) and 26% with B-Symptom.As of the cut-off date for investigator-assessed PFS, duration of response and OS, median follow-up was 23 months (range, 0.5-34) in the CT-P10 group and 22 months (range, 0.2-33) in the RTX group. The proportion of patients who had experienced relapse, disease progression or death from any cause was 22.9% (16/70) and 24.3% (17/70) for the CT-P10 and RTX groups, respectively. There was no significant difference between CT-P10 and RTX groups in PFS (log rank, p-value: 0.806) with 2-year PFS of 75.2% and 73.5%, respectively (Figure 1). In terms of sustained response, the proportions of patient who showed relapse or disease progression after achieving overall response (Complete Response, unconfirmed Complete Response, or Partial Response) were 19.4% (13/67) in CT-P10 group and 21.3% (13/61) in RTX group, and the KM curves showed no statistically significant difference between CT-P10 and RTX (log rank, p-value: 0.997) (Figure 2). Death from any cause were 5.7% (4/70) and 2.9% (2/70) in the CT-P10 and RTX groups, respectively. There was no statistically significant difference in OS (log rank, p-value: 0.464) between the CT-P10 and RTX groups with 2-year OS of 93.2% and 95.3%, respectively.Overall safety profile of CT-P10 was consistent with that of RTX (Table 1). A similar number of patients in each treatment group experienced at least 1 Treatment Emergent Adverse Events (TEAE) considered to be related to the study drug, infusion-related reaction, and infection. The proportion of patients with positive anti-drug antibody was also similar in both groups (4.3% [3/70] vs 5.7% [4/70] in the CT-P10 and RTX groups). Neither progressive multifocal leukoencephalopathy nor Hepatitis B virus reactivation was reported in either group.Conclusion: At the median follow-up duration of 23 months, the updated efficacy data in advanced FL patients demonstrated comparable PFS, sustained response and OS between CT-P10 and RTX. CT-P10 was also well tolerated and its safety profile was similar to that of RTX. The updated safety results did not reveal any trends or new signals noted in the patients treated with CT-P10. [Display omitted] DisclosuresKim:Mundipharma: Research Funding; Novartis: Research Funding; Kyowa-Kirin: Research Funding; Celltrion: Research Funding; Roche: Research Funding; J&J: Research Funding; Takeda: Research Funding. Buske:Roche: Honoraria, Research Funding; Bayer: Research Funding; Janssen: Honoraria, Research Funding. Ogura:MeijiSeika Pharma: Consultancy; Celltrion: Consultancy, Research Funding; Mundi Pharma: Consultancy; SymBio: Research Funding; Takeda: Honoraria; Cellgene: Honoraria. Coiffier:CELGENE: Consultancy, Membership on an entity's Board of Directors or advisory committees; MUNDIPHARMA: Membership on an entity's Board of Directors or advisory committees; CELLTRION: Membership on an entity's Board of Directors or advisory committees; MORPHOSYS: Membership on an entity's Board of Directors or advisory committees; NOVARTIS: Membership on an entity's Board of Directors or advisory committees. Lee:Celltrion, Inc: Employment. Kim:Celltrion, Inc: Employment.

Rituximab for rheumatoid arthrits treatment: a systematic review

IntroductionRheumatoid arthritis (RA) is a chronic autoimmune disease characterized by systemic joint inflammation that often leads to significant disability. Several effective anti-TNF agents have been used, but some patients have shown an inadequate response. Rituximab is a therapeutic monoclonal antibody indicated in such cases. MethodsWe conducted a systematic review to access efficacy and safety of rituximab in patients with active RA which have or have not been treated with anti-TNF agents before, and to relate outcome with RF and anti-CCP serology. We searched major electronics databases, grey literature and searched for references manually. We used Review Manager®5.1 for meta-analysis. ResultsWe included six RCTs comparing rituximab 1000mg with placebo. Methotrexate was used by both groups. Treatment with rituximab was more effective in naïve and in anti-TNF treatment failure patients - ACR20/50/70 and EULAR response. We observed lower changes in Total Genant-modified Sharp score, erosion score and joint narrowing scores in the rituximab group, and SF-36, FACIT-T and HAQ-DI scores were also better in this group. There were no differences between groups regarding safety outcomes, with exception of acute injection reactions, which were more common on rituximab group. More RF/anti-CCP seropositive patients achieved ACR20 than RF/anti-CP negative patients in rituximab group. ConclusionAvailable data support the use of rituximab for the treatment of RA, as it is an effective and safe option for naïve and anti-TNF treatment failure patients. RF and anti-CCP seam to influence treatment results, but this inference needs further research.

Rituximabe para o tratamento da artrite reumatoide: Revisão sistemática

IntroductionRheumatoid arthritis (RA) is a chronic autoimmune disease characterized by systemic joint inflammation that often leads to significant disability. Several effective anti–TNF agents have been used, but some patients have shown an inadequate response. Rituximab is a therapeutic monoclonal antibody indicated in such cases. MethodsWe conducted a systematic review to access efficacy and safety of rituximab in patients with active RA which have or have not been treated with anti–TNF agents before, and to relate outcome with RF and anti–CCP serology. We searched major electronics databases, grey literature and searched for references manually. We used Review Manager®5.1 for meta–analysis. ResultsWe included six RCTs comparing rituximab 1000mg with placebo. Methotrexate was used by both groups. Treatment with rituximab was more effective in naïve and in anti–TNF treatment failure patients ACR20/50/70 and EULAR response. We observed lower changes in Total Genant–modified Sharp score, erosion score and joint narrowing scores in the rituximab group, and SF–36, FACIT–T and HAQ–DI scores were also better in this group. There were no differences between groups regarding safety outcomes, with exception of acute injection reactions, which were more common on rituximab group. More RF/anti–CCP seropositive patients achieved ACR20 than RF/anti–CP negative patients in rituximab group. ConclusionAvailable data support the use of rituximab for the treatment of RA, as it is an effective and safe option for naïve and anti–TNF treatment failure patients. RF and anti–CCP seam to influence treatment results, but this inference needs further research.