Effectiveness Of Rituximab In Patients Research Articles

A Retrospective Evaluation of the Treatment Effects of Rituximab in Patients with Progressive and Symptomatic Fibrosing Mediastinitis.

Fibrosing mediastinitis is an uncommon fibro-inflammatory condition without established or effective medical therapies. Infiltrating B-lymphocytes are commonly present, and progressive fibrosis compromises mediastinal structures including blood vessels and airways resulting in significant morbidity and mortality. To evaluate the benefits and side effects of Rituximab in patients with progressive and symptomatic fibrosing mediastinitis. We treated 22 patients (median age 35 years, range: 15-68 years, 45% female) with metabolically active, progressive fibrosing mediastinitis with off-label rituximab. Additionally, patients were put on pneumocystis and antifungal prophylaxis when immunosuppressed with rituximab. Modeling of longitudinal treatment response based on changes in relative lesion volume from baseline was performed retrospectively using functional data analysis; time-to-event modeling was performed to estimate treatment response rates based on a >30% reduction in pre-treatment volume. The primary end points were lack of disease progression and change in mediastinal lesion volume by CT (evaluated retrospectively). No patient experienced disease progression after rituximab therapy. Median clinical follow-up was 42 months (range: 7 to 94) and imaging follow-up 21 months (range: 7 to 62). 82% of patients had confirmed histoplasmosis-associated fibrosing mediastinitis. After rituximab treatment a 49.6% (95% CI = [17.5%, 64.4%]) mean estimated decrease in pre-treatment lesion volume was observed at 24 months. The estimated objective treatment response rate was 47.9% (95% CI = [26.7%, 70.3%]). This observational study suggests that Rituximab is well tolerated and potentially effective therapy in a cohort of patients with symptomatic and progressive FM.

Pharmacotherapy of autoimmune rheumatic diseases – from monoclonal antibodies to CAR T cells: 20 years later

Autoimmunity is a pathological process associated with a violation of immunological tolerance to normal structural components of the body (autoantigens), associated with the predominance of active (adaptive) immunity and manifested by hyperproduction of autoantibodies. Systemic autoimmune rheumatic diseases (SARDs) are among the most common and severe nosological forms of this pathology associated with autoimmunity. Problems of pharmacotherapy of SARDs are the subject of intensive research. At the beginning of the 21st century, more than 20 biologic agents were developed for the treatment of rheumatoid arthritis – monoclonal antibodies (mAbs) and recombinant proteins that control inflammation associated with the overproduction of “pro-inflammatory” cytokines, the use of which has dramatically improved the results of pharmacotherapy. However, much less research has been devoted to studying the possibilities of pharmacotherapy aimed at selective suppression of the “autoimmune” component of the pathogenesis of SADRs associated with uncontrolled activation of B cells and restoration of immunological tolerance to autoantigens. In the spectrum of drugs whose mechanism of action is associated with the suppression of pathological activation of B cells, the leading place is occupied by rituximab (RTM). It is noteworthy that 20 years ago (2004), a group of researchers led by prof. J.C. Edwards first demonstrated the effectiveness of RTM in patients with RA, which was soon successfully repositioned to treat a wide range of SARDs. A major achievement in the pharmacotherapy of SARDs is associated with the use of CAR (сhimeric antigen receptor) T cell therapy, developed for the treatment of refractory hematological tumors. The main component of CART-cells is a genetically engineered T-cell receptor that recognizes the target antigen without the participation of the major histocompatibility complex. Although limited, extremely impressive data regarding high remission rates have been obtained by adapting CD19 CART-cell therapy to treat patients with severe systemic lupus erythematosus (SLE) and other SARDs refractory to standard immunosuppressive medications. The article discusses the results of the use of CART-cell therapy in SLE and other SARDs and prospects for further research.

Rituximab treatment in resistant lupusnephritis: A single-center prospective study.

Lupus nephritis (LN) is a serious manifestation of systemic lupus erythematosus (SLE) and failure to respond to traditional immunosuppression increases morbidity and mortality. Rituximab has been considered a novel therapeutic option for the management of SLE. We conducted a single-center, prospective, observational study from July 2018 to June 2019 to evaluate the effectiveness of rituximab in patients with resistant LN. Resistant LN was defined as the failure to respond to conventional immunosuppressive therapy including both cyclophosphamide and mycophenolate mofetil. All adult patients (>18 years) with biopsy-proven class III/IV LN were included in the study. Four doses of intravenous rituximab (375 mg/m2) on 0, 1, 2, 3 weeks were administered. Patients were followed for 6months, and the rates of complete renal response (CRR), partial renal response (PRR), or no renal response (NRR) were measured. The change in baseline 24-hour urine protein, mean serum creatinine levels, and mean serum CD-19 levels at 24 weeks were also measured. Six months after rituximab therapy, total sustained renal response (CRR+PRR) was observed in 52% cases of resistant LN (CRR was achieved in 24% of patients and PRR in 28%, respectively). Rituximab was associated with a significant decline in the 24-hour urine protein, even in non-responders. However, the improvement in eGFR and serum creatinine was not statistically significant. The mean absolute CD-19 count was significantly low in responders compared to the non-responder group. Rituximab is a safe and effective therapeutic strategy for patients with resistant LN.

Effect of rituximab in patients with PLA2R-associated membranous nephropathy and malignancy

IntroductionPhospholipase A2 receptor (PLA2R)-associated membranous nephropathy (MN) is a common cause of nephrotic syndrome in nondiabetic adults who are also within the common age group for malignancy. How to treat patients with PLA2R-associated MN and malignancy effectively and safely still requires careful consideration. The aim of our study was to examine the outcomes and safety of rituximab (RTX) in these patients. MethodsRetrospective analysis of clinical data was performed on 15 patients with PLA2R-associated MN and malignancy. Patients were followed every 1–3 months for a minimum of 24 months. Clinical data were collected, including CD19+ B cells, anti-PLA2R antibodies, 24-hour urinary protein, serum albumin, and serum creatinine. The percentage of patients who achieved clinical remission and immunological remission was also measured. ResultsAmong these 15 patients, 14 patients with solid tumors received treatment for malignant diseases with complete resection. One patient received chemotherapy for chronic myeloid leukemia, and achieved complete remission 36 months before the diagnosis of MN. There were 6 (40.00 %) patients who achieved complete remission and 14 (93.33 %) patients who achieved complete or partial remission at the last visit after RTX treatment. At the last visit, patients were clinically improved, as evidenced by significant improvements in anti-PLA2R antibody titer [2.00 (2.00, 2.00) vs 35.25 (11.18, 91.58) RU/ml, P = 0.002], 24-hour urine protein [0.39 (0.11, 2.28) vs 9.22 (4.47, 14.73) g/d, P = 0.001], and serum albumin [38.15 (34.80, 43.20) vs 23.70 (18.70, 25.70) g/L, P = 0.001]. During the follow-up, the renal function of those patients remained stable. Recurrence of malignant tumors or the occurrence of new tumor events were not observed. ConclusionIn this single-center retrospective study with a small sample size, RTX therapy might be an effective and safe treatment in patients with PLA2R-associated MN and malignancy.

Efficacy and safety of rituximab as second-line therapy in immune thrombocytopenic purpura based on ethnicity: A descriptive study among the Arabic population.

Background: Rituximab is used as second-line therapy in patients with immune thrombocytopenic purpura (ITP) who do not respond to first-line management. The response rate for Rituximab is variable in different populations ranging from 30% to 90%. The adverse effects of rituximab in patients with ITP range from infusion site reactions to the reactivation of hepatitis B virus and progressive multifocal leukoencephalopathy and interpopulation variation.Methods: We conducted a single-center, retrospective study in Qatar's National Center for Cancer Care & Research. The study included patients with chronic refractory ITP who received rituximab as second-line therapy. Descriptive and summary statistics were used to describe the sociodemographic parameters of the study cohort.Results: Of the 41 patients with chronic ITP, 26 were Arabs, 12 were Asians, and 3 were of other ethnicities. Rituximab was associated with an overall response rate of 80.4%. Arabic patients had the highest clinical response (84.6%) among the ethnicities with the lowest adverse effects (11.5%). Asians had a response rate of 66.6%, and adverse effects were seen in 16.7% of the patients.Conclusions: In chronic refractory ITP, rituximab appears to have a better clinical response in the Arabic population with minimal toxicity than in other ethnicities.

Rituximab in myasthenia gravis: efficacy, associated infections and risk of induced hypogammaglobulinemia

The aim of this study is to evaluate the long-term efficacy, safety, and impact on immunoglobulin G (IgG) levels of rituximab in patients with myasthenia gravis (MG). A retrospective, observational study of drug-refractory MG patients treated with rituximab was done. The MG Foundation of America postintervention status (MGFA-PIS) was used to evaluate clinical response. Serum IgG levels were determined at baseline and post-treatment. Hypogammaglobulinemia was defined as IgG<7g/L. Thirty patients were included, 12 with anti-MuSK and 18 with anti-AChR antibodies. Mean (SD) follow-up was 85.5 (48) months. All 12 MuSK+ patients but only six (33%) AChR+ patients achieved minimal manifestations or remission (p<0.01). Nine severe infections were observed in five patients (17%). One patient was diagnosed with progressive multifocal leukoencephalopathy. At baseline, two patients (2/24; 8%) had hypogammaglobulinemia. During follow-up, hypogammaglobulinemia was observed in 60% (3/5) of patients who developed an infection and in 33% (7/21) who did not. Two of these patients died of infection-related complications. This study supports the effectiveness of rituximab in patients with MG, especially those with anti-MuSK antibodies. Severe infections may appear after rituximab treatment and hypogammaglobulinemia might play a role on it. A standard protocol would be needed to closely monitor IgG levels in MG patients treated with rituximab.

Efficacy and safety of an anti-CD20 monoclonal antibody, rituximab, for lupus nephritis: A meta-analysis.

The efficacy and safety of rituximab (RTX) for lupus nephritis are still a controversial issue. We systematically searched MEDLINE, EMBASE, and the Cochrane Library databases for all clinical controlled studies. Six studies with 588 patients were included in our meta-analysis. RTX increased total renal remission rates (TR, odds ratio [OR] 2.16, 95% CI 1.31 to 3.55, P=.003) and complete renal remission rate (CR, OR 2.42, 95% CI 1.18 to 4.94, P=.02) compared with the control group. Subgroup analyses showed that rituximab was more effective at increasing the rate of TR and CR for lupus nephritis patients compared with mycophenolate mofetil (TR, OR 4.6, 95% CI 1.29 to 16.47, P=.02; CR, OR 2.56, 95% CI 1.19 to 5.47, P=.02) and cyclophosphamide (TR, OR 2.89, 95% CI 1.31 to 6.40, P=.009; CR, OR 2.75, 95% CI 1.19 to 6.4, P=.02). Rituximab also had advantage in reducing Systemic Lupus Erythematosus Disease Activity Index score (-2.49, 95% CI -3.77 to -1.22, P=.0001). There were no significant differences between the RTX group and control group on the change of proteinuria (-0.36g/d, 95% CI -0.71 to -0.00g/d, P=.05) and serum creatinine (0.13mg/dL, 95% CI -0.15 to 0.42mg/dL, P=.36). RTX treatment did not increase the risk of adverse events compared to the control group. This study provides clear beneficial effects of RTX in patients with lupus nephritis. In addition, RTX therapy did not increase the risk of adverse events compared to the control group.

O17 Effectiveness of rituximab in the treatment of neuro-psychiatric SLE: results from the British Isles Lupus Assessment Group Biologics Register

Abstract Background/Aims Neuro-psychiatric (NP) involvement in systemic lupus erythematosus (SLE) can occur in 56.3% cases. Rituximab (RTX) has been demonstrated to be safe and efficacious in the treatment of refractory SLE although there is limited evidence for its use in NP-SLE. We aim to describe the baseline characteristics and short-term effectiveness of RTX in patients treated for NP-SLE within the British Isles Lupus Assessment Group Biologics Register (BILAG-BR). Methods Patients with active NP involvement; scoring BILAG A or B and/or on SLEDAI-2K were included. Baseline characteristics, disease activity and oral steroid dose pre and 5 - 9 months post-treatment were analysed. Paired Wilcoxon-Signed-Ranked Test was used to determine changes in disease activity scores and steroid dose. Results We identified 74 patients of whom 61 (82%) were female and 48 (74%) Caucasian. Median age [interquartile range (IQR)] was 45.5 years [37 - 58] and disease duration 11.5 years [7 - 18.8]. 68 patients had active disease on BILAG (A = 34, B = 34) with 6 scoring on SLEDAI-2K only. The majority (n = 71/74, 96%) had at least one other organ involved. Central nervous system (CNS) disease occurred in 45/65 (69%) cases, 12/65 (18%) had peripheral nervous system (PNS) disease and 8/65 (12%) CNS/PNS overlap. Anti-Ro was the commonest identified antibody (n = 26/57, 46%) and 42 of 59 (71%) patients had a raised anti-dsDNA and/or low complement. The majority (n = 64/74, 86%) were taking glucocorticoids and median prednisolone dose was 15mg [IQR 10 - 20]. Pre and post-RTX BILAG, total SLEDAI-2K and oral steroid dose were available in 50, 57 and 27 patients respectively. Following RTX, patients with NP BILAG A or B reduced from 50 to 11 (p &amp;lt; 0.0001). 4 of the 6 patients with NP-SLE on SLEDAI-2K alone, improved. Total median SLEDAI-2K score reduced from 12 [IQR 14 - 18] to 2 [IQR 0 - 4] (p &amp;lt; 0.0001). Median steroid dose reduced from 15mg [IQR 11.3 - 25] to 10mg [IQR 6.9 - 18.8] (p = 0.009). For 53 patients, active CNS, PNS and overlap disease reduced from 37 (70%) to 6 (11%), 10 (19%) to 3 (6%) and 6 (11%) to 4 (8%) respectively. In 9 patients treated with concomitant CYC, none had persistent NP disease. In contrast, 11 of 41 patients who had RTX alone had persistent NP disease. Conclusion RTX use is associated with improvement in NP-SLE with reduction in oral steroid dose. Concomitant CYC may enhance the level of improvement seen with RTX. Large scale studies are therefore warranted to establish the effectiveness of RTX alone or in combination with CYC in the treatment of NP-SLE. Disclosure T. David: None. R. Hum: None. E. Sutton: None. B. Parker: None. E. McCarthy: None. I. Bruce: None.

A prospective observational study on efficacy of serial low dose infusion of rituximab (500 mg) on patients of pemphigus

&lt;p class="abstract"&gt;&lt;strong&gt;Background:&lt;/strong&gt; Rituximab (RTX) is a chimeric anti-CD20 monoclonal antibody being increasingly used in management of pemphigus. Various studies show a lack of any uniform treatment protocol. The objective of the study was to assess the effectiveness of RTX in patients of pemphigus receiving serial low doses of RTX (500 mg; maximum of 4 doses; 2 weeks apart).&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Methods: &lt;/strong&gt;It was a prospective observational review of 40 pemphigus patients to assess the proportion of patients achieving complete remission after serially receiving low dose RTX, time and number of doses required to achieve complete remission (CR), proportion of patients who responded partially or didn’t respond or relapsed after achieving CR. Additionally, the study was done to find whether a correlation existed between age, gender, and site of lesion and RTX administration.&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Results: &lt;/strong&gt;40 pemphigus patients followed up for a mean duration (MD) of 174.15±95.67 days received 4 doses of RTX (500 mg) irrespective of the disease activity 0.30 (75%) attained CR on therapy with ≥3 doses of RTX 500 mg (MD= 76.39±34.45 days) and azathioprine 100 mg/day. No patients relapsed after 4 doses while 3 (7.5%) patients didn’t respond. Oral lesions and pemphigus vulgaris took more time for achieving CR.&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;While we reinforce the idea of using more than 3 doses of RTX 500 mg in a view to achieve prolonged remission we promote considering usage of a more cost-effective drug like azathioprine for maintaining remission especially in a poor remote tertiary center in India with limited resources. Immunological assays were not performed limiting the study.&lt;/p&gt;

THU0143 EFFECT OF RITUXIMAB OR TUMOUR NECROSIS FACTOR INHIBITORS ON LUNG INFECTION AND 5-YEAR SURVIVAL IN RHEUMATOID ARTHRITIS-ASSOCIATED BRONCHIECTASIS

Background: Bronchiectasis (BR) is a significant pulmonary morbidity common in people with rheumatoid arthritis (RA). Patients with RA and bronchiectasis (RA-BR) often have severe arthritis but the use of biologics may be difficult in this group of patient due to concerns over safety. There is no data comparing the use of rituximab (RTX) and tumour necrosis factor inhibitors (TNFi) in RA-BR. Objectives: To evaluate the effect of RTX in patients with RA-BR and compare 5-year respiratory survival between those treated with RTX and TNFi. Methods: A retrospective observational cohort study of RA-BR was conducted in RTX or TNFi-treated RA patients from two UK centres over 10 years. BR was assessed using number of infective exacerbations/year. Respiratory survival was defined as time from therapy initiation to discontinuation either due to lung exacerbation or lung-related deaths. Results: Of 800 RTX-treated RA patients, 68 had RA-BR (prevalence 8.5%). Post-RTX, new BR was diagnosed in 3/735 patients (incidence 0.4%). At 12 months post-Cycle 1 RTX, 21/68 (31%) patients had fewer exacerbations than the year pre-RTX, 36/68 (53%) remained stable and 11/68 (16%) had increased exacerbations. In multivariable analysis, a factor associated with increased risk of this initial exacerbation was pseudomonas colonisation [OR 7.23 (95% CI 1.28-40.80)] while older age reduced risk [OR 0.44 (95% CI 0.21-0.90) per 10 years of age]. The rates of exacerbation improved after Cycle 2 RTX and stabilised up to 5 cycles. Of patients who received ≥2 RTX cycles (n=60), increased exacerbations occurred in 7/60 (12%) and were associated with low IgG, aspergillosis and concurrent alpha-1-antitrypsin deficiency. Respiratory survival was compared between RA-BR patients treated with RTX (N=68) or TNFi (N=46). Most characteristics were matched but median (IQR) number of infective exacerbations/year in the previous 12 months pre-bDMARDs was higher in those treated with RTX than TNFi; 3.0 (1-4) and 0 (0-2) respectively. Overall, 8/68 (11.8%) patients discontinued RTX while 15/46 (32.6%) discontinued TNFi due to respiratory causes. The adjusted 5-year respiratory survival was better in RTX-treated compared to TNFi-treated RA-BR patients; HR 0.40 (95% CI 0.17–0.96); p=0.041. Conclusion: The majority RA-BR patients had stable or improved pulmonary symptoms during RTX therapy over a prolonged follow-up period. In isolated cases, worsening of exacerbation after RTX therapy had definable causes. Despite a higher rate of exacerbations pre-biologic, rates of discontinuation due to adverse lung outcomes were better for RTX than a matched TNFi cohort. RTX appears to be an acceptable therapeutic choice for RA-BR if a biologic is needed. Disclosure of Interests: Md Yuzaiful Md Yusof: None declared, Kundan Iqbal: None declared, Michael Darby: None declared, Giovanni Lettieri: None declared, Edward Vital Grant/research support from: AstraZeneca, Roche/Genentech, and Sandoz, Consultant of: AstraZeneca, GSK, Roche/Genentech, and Sandoz, Speakers bureau: Becton Dickinson and GSK, Paul Beirne: None declared, Shouvik Dass Grant/research support from: Roche and GSK, Paul Emery Grant/research support from: AbbVie, Bristol-Myers Squibb, Merck Sharp & Dohme, Pfizer, Roche (all paid to employer), Consultant of: AbbVie (consultant, clinical trials, advisor), Bristol-Myers Squibb (consultant, clinical trials, advisor), Lilly (clinical trials, advisor), Merck Sharp & Dohme (consultant, clinical trials, advisor), Novartis (consultant, clinical trials, advisor), Pfizer (consultant, clinical trials, advisor), Roche (consultant, clinical trials, advisor), Samsung (clinical trials, advisor), Sandoz (clinical trials, advisor), UCB (consultant, clinical trials, advisor), Clive Kelly Consultant of: Boehringer Ingelheim, Speakers bureau: Boehringer Ingelheim

Efficacy and Safety of Rituximab in Refractory CIDP With or Without IgG4 Autoantibodies (RECIPE): Protocol for a Double-Blind, Randomized, Placebo-Controlled Clinical Trial.

BackgroundChronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an immune-mediated peripheral neuropathy that is currently classified into several clinical subtypes, which are presumed to have different pathogenic mechanisms. Recently, studies identified a subgroup of patients with CIDP who were positive for IgG4 autoantibodies against paranodal proteins, such as neurofascin-155 and contactin-1, who respond poorly to first-line therapies for typical CIDP, including intravenous immunoglobulin therapy.ObjectiveThis study aims to evaluate the efficacy and safety of intravenous rituximab according to IgG4 autoantibody status in patients with refractory CIDP.MethodsThe Evaluation of the Efficacy and Safety of Rituximab in Refractory CIDP Patients with IgG4 Autoantibodies in the Exploratory Clinical (RECIPE) trial consists of 2 cohorts: a multicenter, placebo-controlled, randomized study cohort of 15 patients with IgG4 autoantibody-positive CIDP (rituximab:placebo = 2:1) and an open-label trial cohort of 10 patients with antibody-negative CIDP. The primary endpoint is improvement in functional outcome assessed using the adjusted Inflammatory Neuropathy Cause and Treatment Disability Scale score at 26, 38, or 52 weeks after the start of treatment with rituximab in patients with CIDP and anti-paranodal protein antibodies. Secondary outcome measures include grip strength, manual muscle testing sum scores, results of nerve conduction studies, and other functional scales.ResultsWe plan to enroll 25 cases for the full analysis set. Recruitment is ongoing, with 14 patients enrolled as of January 2020. Enrollment will close in September 2020, and the study is planned to end in December 2021.ConclusionsThis randomized controlled trial will determine if rituximab is safe and effective in patients with anti-paranodal antibodies. An open-label study will provide additional data on the effects of rituximab in patients with antibody-negative CIDP. The results of the RECIPE trial are expected to provide evidence for the positioning of rituximab as a pathogenesis-based therapeutic for refractory CIDP.Trial RegistrationClinicalTrials.gov NCT03864185, https://clinicaltrials.gov/ct2/show/NCT03864185 ; The Japan Registry of Clinical Trials jRCT2041180037, https://jrct.niph.go.jp/en-latest-detail/jRCT2041180037International Registered Report Identifier (IRRID)DERR1-10.2196/17117

Rituximab effect in severe progressive connective tissue disease-related lung disease: preliminary data.

Progressive connective tissue disease (CTD)-related lung disease is a challenging condition that requires lung transplantation in some patients. Treatment with rituximab may improve lung function. To evaluate the effect of rituximab in patients with progressive CTD-related lung disease who met criteria for inclusion in waiting list for a lung transplant. Retrospective study of patients with progressive CTD-related lung disease with criteria for lung transplant (FVC < 60% and/or DLCO < 40%) that started treatment with rituximab because of disease progression. Clinical variables, pulmonary function tests and chest computed tomography were used to monitor the effect of rituximab. The cohort included 18 patients; systemic sclerosis (7), rheumatoid arthritis (5), systemic lupus erythematosus (4), Sjögren syndrome (1) and antisynthetase syndrome (1). The radiologic patterns observed were: usual interstitial pneumonia (1), non-specific interstitial pneumonia (9), lymphoid interstitial pneumonia (1), emphysema-usual interstitial pneumonia (1), shrinking lung syndrome (3) and undetermined pattern (3). Over the previous year to rituximab initiation a decline in FVC (- 3.8%, p = 0.095) and DLCO (- 8.4%, p = 0.004) was observed. After 2years of treatment, DLCO significantly improved (+ 12.4%, p < 0.001 at 1year and + 15.3%, p = 0.001 at 2years). Six patients (33.3%) presented adverse events related to rituximab. No patient required lung transplant or died during the study period. Rituximab is an effective treatment for patients with severe and progressive CTD-related lung disease, which allows to delay lung transplantation in some cases.

Experience of application of rituximab with resistant focal-segmental glomerulosclerosis in adults: a series of observations and a brief review of literature

Steroid-resistant focal-segmental glomerulosclerosis (FSGS) with nephrotic syndrome (NS) is a progressive kidney disease with the rapid development of end-stage renal failure (ESRD). In recent years, attempts have been made to treat steroidresistant FSHS with anti-CD20 monoclonal antibodies, rituximab. Currently, only a few clinical case reports and series with contradictory results have been published. THE AIM of our study was to evaluate the effect of rituximab in patients with resistant to the therapy focal segmental glomerulosclerosis. MATERIALS AND METHODS : The study included 6 patients with confirmed diagnosis of FSGS. The inclusion criteria were the presence of steroid-resistant NS or to the other treatment regimens, including cyclosporin A, tacrolimus, mycophenolate mofetil, cyclophosphamide, and exclusion criteria were the secondary form of the disease. Patients were treated with one course of rituximab – 2 to 4 infusions (the total dose was 1.0–2.0 g). Laboratory parameters (daily proteinuria, albumin and eGFR CKD-EPI) were analyzed before rituximab, as well as 6 and 12 months after treatment. RESULTS : A partial remission of FSGS was achieved in one patient, stable renal function was maintained for 12 months follow-up. In 4 out of 6 patients, progression of the disease was observed with the development of ESRD in the period from 1 to 3 years, despite a decrease in the severity of NS. In one patient, the NS of the same severity persisted for 6 months after the treatment; no positive dynamics in proteinuria or serum proteins were observed. CONCLUSION : Thus, we did not show a significant effect of rituximab in patients with steroid-resistant FSGS. However, according to the literature the effect of rituximab has been achieved in approximately half of steroid-resistant FSGS cases, therefore further prospective clinical trials are needed.

Rituximab in primary central nervous system lymphoma-A systematic review and meta-analysis.

The CD-20 antibody rituximab is a standard component of treatment of non-Hodgkin B-cell lymphomas, including diffuse large B-cell lymphoma (DLBCL). Primary DLBCL of the central nervous system, also called primary central nervous system lymphoma (PCNSL), is a DLBCL confined to the central nervous system. There has been debate whether intravenous rituximab accumulates sufficiently in the central nervous system to exert an effect. In this systematic review, we assess the benefits and harms of rituximab in the treatment of immunocompetent patients with PCNSL. By searching MEDLINE, CENTRAL, and ClincialTrials.gov up to March 2019, we identified randomized controlled trials (RCTs) investigating the effect of rituximab in patients with PCNSL. We extracted study characteristics and results, assessed risk of bias, performed trial-level random-effects meta-analyses, and graded the certainty of evidence. The protocol was registered with PROSPERO (CRD42019121965). Main outcomes were overall survival (time to death), progression-free survival (time to progression or death), quality of life, grades 3 and 4 toxicity, and treatment-related mortality. We included two RCTs with a total of 343 participants. Overall survival was not statistically significantly improved (HR 0.76; 95% CI, 0.52-1.12; low certainty), with 187 fewer to 39 more deaths after 2 years in 1000 treated patients. Low certainty of evidence indicated that rituximab improved progression-free survival (HR 0.65; 95% CI, 0.45-0.95), which translated into 137 fewer progressions or deaths after 2 years in 1000 treated patients (231 to 18 fewer). None of the RCTs provided data on quality of life. We found no evidence that rituximab increased grades 3 and 4 toxicity or treatment-related mortality (RR 0.53; 95% CI, 0.20-1.37; low certainty). Overall, the available evidence suggests with low certainty that rituximab in combination with methotrexate-based chemotherapy may improve progression-free survival in immunocompetent patients with newly diagnosed PCNSL, the pooled effect estimates did not show evidence for improvement of overall survival.

Rituximab maintenance therapy for patients with diffuse large B-cell lymphoma: A meta-analysis.

PurposeThe addition of rituximab to standard chemotherapy has significantly improved survival in patients with lymphoma. Recently, maintenance therapy with rituximab has been shown to prevent relapse and provide survival benefits for patients with follicular or mantle cell lymphoma. However, the effects of rituximab in patients with diffuse large B-cell lymphoma (DLBCL) remain unclear. Two new studies involving rituximab in the treatment of DLBCL were performed this past year. We performed a meta analysis to evaluate the effects of rituximab maintenance treatment of patients with DLBCL.MethodsSeveral databases (PubMed, MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials) databases were reviewed for relevant randomized controlled trials published prior to May, 2016. Two reviewers assessed the quality of the included studies and extracted data independently. The hazard ratios (HRs) for time-to-event data and relative risks (RRs) for the other data were pooled and estimated.ResultsTotally 5 studies including 1740 patients were eligible for the meta-analysis. Compared to the observation group, patients who received rituximab maintenance therapy had significantly improved event-free survival (EFS) (HR = 0.80, 95% CI: 0.65–0.98) and progression-free survival (PFS) (HR = 0.72, 95% CI: 0.54–0.94). However, there was no statistically significant difference in overall survival (OS) (HR = 0.66, 95% CI: 0.27–1.29). A subgroup analysis suggested that male patients may benefit from rituximab maintenance therapy with a better EFS (HR = 0.53, 95% CI: 0.34–0.82-), while this advantage was not observed in female patients (HR = 0.99, 95% CI: 0.64–1.52).ConclusionsRituximab maintenance may provide survival benefits beyond that afforded by first- and second-line chemotherapy alone, especially in male patients. However, maintenance rituximab treatment may cause more adverse events. It is recommended that both survival benefits and adverse events should be taken into consideration when making treatment decisions.

Lymphoma Secondary to Congenital and Acquired Immunodeficiency Syndromes at a Turkish Pediatric Oncology Center

The prevalence of lymphoma in primary immunodeficiency cases and autoimmune diseases, as well as on a background of immunodeficiency following organ transplants, is increasing. The lymphoma treatment success rate is known to be a low prognosis. Our study aimed to emphasize the low survival rates in immunodeficient vs. immunocompetent lymphoma patients and also to investigate the effect of rituximab in patients with ataxia telangiectasia and other immunodeficiencies. We summarized the clinical characteristics and treatment results of 17 cases with primary immunodeficiency that developed non-Hodgkin lymphoma (NHL) and Hodgkin lymphoma (HL) retrospectively. Seven patients were diagnosed with ataxia-telangiectasia, two with common variable immunodeficiency, two with selective IgA deficiency, one with X-related lymphoproliferative syndrome, one with Wiskott-Aldrich syndrome, one with Epstein-Barr virus-related lymphoproliferative syndrome, one with interleukin-2-inducible T-cell kinase (ITK) deficiency, and one with lymphoma developing after autoimmune lymphoproliferative syndrome (ALPS). One patient underwent a renal transplant. Of the nine males and eight females (aged 3-12years, median = 7) that developed lymphoma, seven were diagnosed with HL and ten with NHL (seven B-cell, three T-cell). The NHL patients were started on the Berlin-Frankfurt-Münster, POG9317, LMB-96, or R-CHOP treatment protocols with reduced chemotherapy dosages. HL cases were started on the doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) and/or cyclophosphamide, vincristine, procarbazine, and prednisone (COPP) protocol, also with modified dosages. Importantly, all seven cases of HL are alive and in remission, while six of the ten NHL patients have died. Primary immunodeficiency is a strong predisposing factor for developing lymphoma. Low treatment success rates relative to other lymphomas and difficulties encountered during treatment indicate that new treatment agents are needed. While some success has been achieved by combining rituximab with lymphoma treatment protocols in B-NHL cases with primary immunodeficiency, the need for new treatment approaches for these patients remains critical.

OP0046 Effect of Rituximab in Patients with Lupus Nephritis during Long-Term Follow-Up

ObjectivesThe aim of this study was to evaluate the long-term clinical, serological and histopathological effects of the therapy with Rituximab (RTM) in patients with lupus nephritis (LN) refractory to conventional...

Impact of rituximab trials on the treatment of ANCA-associated vasculitis

ANCA-associated vasculitis (AAV) is a subgrouping of autoimmune disorders characterized by a chronic relapsing course. Induction therapy is usually effective, but 70% of patients will relapse and 20% develop refractory disease. In the relapsing and refractory subgroups, treatment is complicated by the cumulative exposure to toxic drugs that contribute to poor long-term outcomes. The anti-CD20 monoclonal antibody rituximab (RTX) depletes B cells, and the success of this targeted therapy has contributed to the evidence supporting a central role for B cells in AAV pathogenesis. Initial proof of RTX effectiveness originated from small, prospective trials and retrospective surveys conducted in AAV patients with relapsing and refractory disease; high remission rates permitted the reduction of glucocorticoids (GCS) doses and withdrawal of immunosuppressives. There has been controversy over the effectiveness of RTX in patients with predominantly granulomatous manifestations, where response rates have varied between studies, in part due to different RTX dosing regimens. These studies were followed by comparison of RTX against cyclophosphamide (CYC) for remission induction of new or relapsing AAV in two randomized trials, which led to the licensing of RTX for this indication. Subsequent attention has been turned to the use of RTX as a relapse prevention agent, to the potential for GCS sparing and to RTX-associated toxicity. We will discuss the impact that the results of RTX clinical trials have had on the management of AAV patients.

Effect of Rituximab in Patients with Cyclophosphamide-non-responsive Connective Tissue Disease-Related Interstitial Lung Disease: A Case Series Study

Objective: To report our experience of intravenous cyclophosphamide pulse therapy and the effect of rituximab (RTX) therapy in patients with cyclophosphamide-non-responsive connective tissue disease associated interstitial lung disease (CTD-ILD).Methods: We retrospectively evaluated the medical records of patients with CTD-ILD. All patients received intravenous cyclophosphamide pulse (IVCYC) therapy. The patients who received IVCYC+RTX were non-responsive to IVCYC treatment. At 0 to 6 months prior to the treatment, these patients underwent a pulmonary function test (PFT). High resolution computed tomography was performed before the initiation of treatment.Results: Ten patients were enrolled in this study. A significant percentage of patients showed stabilization or improvement of pulmonary function after treatment. The response rates of the IVCYC and IVCYC+RTX groups were 50% (5/10) and 60% (3/5), respectively.Conclusions: Patients with CTD-ILD who received IVCYC with or without RTX therapy showed a significant improvement in lung function. RTX therapy could be employed as a salvage therapy and combined with IVCYC early for refractory CTD-ILD.

Beneficial effects of Rituximab in patients with anti-MAG (myelin-associated glycoprotein) neuropathy: case reports

Anti-myelin-associated glycoprotein (MAG) neuropathy is a primary demyelinating sensorimotor polyneuropathy that can be very debilitating and is known to be resistant to treatment. There are only a few conflicting reports on the effect of Rituximab in anti-MAG neuropathy. We present three patients who improved remarkably with Rituximab infusions. Until the safety and efficacy of this drug are determined in larger controlled studies, use of Rituximab should be limited to patients with significant neurologic deficits.