Course Of Rituximab Research Articles

Granulomatosis with polyangiitis with severe lung involvement: efficacy of anti-B cell therapy with Rituximab

The present report illustrates efficacy of rituximab (RTX) in granulomatosis with polyangiitis (GPA) with severe lung involvement. Female patient, 45 years old, was ill since March 2016, her disease manifested at the onset with fever, recurrent epistaxis, otitis media, mastoiditis, conjunctivitis and arthritis. Thoracic CT scan showed multiple decaying pulmonary infiltrates. The presence of PR3-ANCA confirmed the diagnosis of GPA. Induction therapy included high doses of glucocorticoids, cyclophosphamide (total dose 4 g), with following azathioprine and mycophenolate mofetil. Lung disease continued to progress with emerging extensive infiltrates and forming a giant cavity with air-fluid level in the right lung. Further treatment included antibiotics followed by surgical draining of lung cavity in December 2018. Fever, necrotic rhinitis and otitis persisted despite treatment, lab findings included red blood cells in the urine, C-reactive protein 90 g/l, thrombocytosis 740×109/l, anemia (Hb 80 g/l). RTX 2 g and intravenous immunoglobulin were initiated in December 2018, a second course of RTX (0.5 g) was administered 4 months later. Patient’s condition was gradually improving, CT scan at 6 months after RTX treatment showed fibrous tissue in the area of former cavity. One year later, total RTX dose was 3.5 g, further regression of changes and GPA remission were achieved. There were no adverse reactions. Anti-B cell therapy with RTX is a safe and highly effective option in GPA patients with severe destructive lung disease, potentially curative even in cases of giant pulmonary cavities.

Noninfectious, Severe Cryoglobulinemic Vasculitis with Renal Involvement – Safety and Efficacy of Long-Term Treatment with Rituximab

BackgroundThe management of nonviral cryoglobulinemic vasculitis (CV) has not been established yet. Randomized control trials are challenging to perform because of the rarity of the disease. The most promising biological therapy is rituximab (RTX), an anti-CD 20 monoclonal antibody. The aim of the study was to assess rituximab treatment’s safety and effectiveness in patients with severe noninfectious cryoglobulinemic vasculitis.Materials and MethodsWe retrospectively reviewed 8 courses of RTX treatment in three patients with severe noninfectious CV. In 2 patients, the indication for the start of RTX therapy was the relapse of the disease despite the maintenance treatment, for the third patient, it was the first-line therapy.ResultsClinical, renal, and immunologic efficacy was observed in all evaluable RTX courses. We found a significant decrease of cryoglobulins in the 3-rd month from RTX treatment. However, 5 clinical relapses occurred and two patients experienced severe adverse events (SAEs) after RTX therapy. Patients with SAEs were relatively older and had a longer duration of disease. Lower levels of hemoglobin, C3 component of complement and eGFR as well as higher rheumatoid factor (RF) concentration were observed before RTX treatments complicated with SAEs.ConclusionData from our observation show the efficacy of rituximab in the refractory, nonviral cryoglobulinemic vasculitis with a severe course of the disease. However, the therapy is associated with the risk of SAEs, especially in elderly patients with kidney failure and significant immunologic alterations.

177 Lu-Lilotomab Satetraxetan, a Novel CD37-Targeted Antibody-Radionuclide Conjugate in Relapsed Non-Hodgkin's Lymphoma (NHL): Updated Results of an Ongoing Phase I/II Study (LYMRIT 37-01)

177 Lu-Lilotomab Satetraxetan, a Novel CD37-Targeted Antibody-Radionuclide Conjugate in Relapsed Non-Hodgkin's Lymphoma (NHL): Updated Results of an Ongoing Phase I/II Study (LYMRIT 37-01)

Circulating myeloid-derived suppressor cells and regulatory T cells as immunological biomarkers in refractory/relapsed diffuse large B-cell lymphoma: translational results from the R2-GDP-GOTEL trial

BackgroundThe search for immunological markers with ability of predicting clinical outcome is a priority in lymphomas, and in cancer in general. It is well known that some immunomodulatory cells, such...

AB0243 CONSIDERING THE COMBINATION OF TWO BIOLOGICS IN CASE OF FAILURE OF THE MONOTHERAPY IN JUVENILE ONSET RHEUMATOID ARTHRITIS

Background:The management of rheumatoid arthritis refractory to conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) is currently well codified and includes different types of biologics and even targeted sDMARDs. A rotation of biologic therapies is recommended in order to better control the disease.Methods:We report the case of a 20-year-old patient followed in our hospital for the management of a deforming and erosive seropositive rheumatoid arthritis (FR +, ACPA +) with a juvenile onset at the age of 8 years. The diagnosis of an immunopositive polyarticular form of JIA was retained in 2010 (9 years old); the patient was treated with methotrexate (MTX) at a dose of 10 mg per week and methylprednisolone at doses varying between 4 and 10 mg per day. Following the failure of MTX, etanercept was introduced for 6 months without success, followed by tocilizumab in 2012 at a dose of 8mg/kg/month for a year, without good response. In 2014, a course of rituximab (RTX) at a dose of 2 shots of 500mg, 2 weeks apart was prescribed followed 9 months later by etanercept at a dose of 50 mg a week for 3 years then by adalimumab (40mg/ week) because of the multiple treatment failures.In 2018, the repetition of RTX at a dose of 1g, renewed 15 days later, improved the patient for only 3 months. Then, a combination of two biologics, namely RTX (2 x 1g, 15 days apart) and adalimumab 1 month later (40mg / week) was received by the patient with a good response at 3 months. The latter was maintained for 7 months even after stopping the adalimumab following confinement for COVID-19. In September 2020, flares occurred and the adalimumab (ADA) has been delivered but without success during 3 months, stopped later for a benign form of COVID-19 (15 months after RTX). In January 2021, the association RTX + ADA was given again and we hope that it will be as effective as the first prescription.Results:The clinical and biological severity of our patient’s rheumatoid arthritis led us to give a combination of two biological treatments. Indeed, we do not have other therapeutic classes to deliver to her, that encouraged us to rotate between all the available biological therapies in our country. The combination of a CD20 inhibitor (RTX) with a TNF blocker (ADA) was safe and made possible, for the first time, the achievement of clinical and biological remission during 7 months, even after stopping the TNF blocker. Greenwald et al. reported the safety of the combination of RTX + TNF inhibitors in a randomized clinical trial in 51 patients. Its efficacy, a secondary goal of the study, was suggested at 24 weeks by the percentage of ACR 20 and ACR 50 responses that was greater than in the RTX placebo group.Conclusion:The combination of RTX with a TNF blocker can be a real alternative therapy in rheumatoid arthritis with failure to a biological monotherapy.Disclosure of Interests:None declared

Randomized Clinical Trial to Compare Efficacy and Safety of Maintenance Mycophenolate-Mofetil to Cyclosporine After Repeated Courses of Rituximab in Children With Steroid Resistant Nephrotic Syndrome

Background: Approximately 10% of children with children with idiopathic nephrotic syndrome will not achieve complete remission after 6-8 weeks therapy with corticosteroid and have steroid resistant nephrotic syndrome (SRNS). Rituximab (RTX), a B cell depleting monoclonal antibody followed by maintenance mycophenolate-mofetil (MMF) or cyclosporine (CYC) has been shown to be efficacious in children with SRNS. Controlled trial comparing the efficacy and safety of treatment with CYC to MMF after RTX induction is lacking. Methods: A total of 55 children with SRNS were randomized to receive 12 months MMF 1.0 g/m2/day (n=28) or CYC 5 mg/kg/day (n=27) following RTX infusions (375 mg/m2 intravenously) to maintain persistent B cell depletion. The primary outcome was complete remission rate at 12 months and secondary outcome consisted of incidence of treatment-related adverse events among all intention-to-treat population. Results: RTX/MMF therapy was associated with a significantly higher relapse-free survival (complete remission rate) at 12-month [23(82% vs. [15(56%)]; p<0·01). Among patients who experienced relapse; median time to first relapse was significantly longer for patients treated with RTX/MMF (10·3 months) than patients receiving RTX/CYC (7·1 months) (P<0·01). Only 3 patients in the RTX/MMF group had more than 1 relapse during the study period compared with 8 in the RTX/CYC group (p<0·01). Overall, the response to therapy was greater in patients with the FSGS who were receiving RTX/MMF regimen (p<0·01). Moderate to severe infections were twice as common in the RTX/CYC than in RTX/MMF (P=0·05). Interpretation: The study found a superiority of MMF over CYC after RTX in terms of relapse -free survival and adverse events. The findings suggest that MMF therapy following RTX may be considered first line corticosteroid-sparing therapy in the treatment of SRNS. Trial Registration: The study was registered with the WHO International Clinical Trials Registry Platform (ICTRP) and Iranian Registry of Clinical Trials (IRCT20150421021894N; https://irct.ir), registration date 25 March 2019. Funding Statement: None. Declaration of Interests: The authors declare they have no financial competing interests for the overall trial and the study site. Ethics Approval Statement: The study protocol and consent documents were approved (IR.ZAUMS.REC.1397.491) by the Ethics committee (Institutional Review Board) of Zahedan University of Medical Sciences, Iran following approval of institute scientific committee. All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research where the study was conducted and with the 1964 Helsinki Declaration and its later amendments as revised in 2013 and confirmed to the CONSORT 2010 checklist guidelines for reporting the randomized clinical trial. Informed written parental consent was obtained from all subjects prior to study.

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.

The results of investigating the efficacy and safety of non-medical switching from the original rituximab to its biosimilar in rheumatoid arthritis patients (AMBIRA study)

Wide usage of biologic disease-modifying anti-rheumatic drugs (DMARDs) biosimilars in clinical practice has greatly increased the availability of biologic therapy for rheumatic patients. Nevertheless, not only economic expediency but efficacy and safety are the key principals of any treatment including biologic DMARDs. Objective . To investigate the efficacy and safety of switching from the original rituximab (MabThera®, “F. Hoffmann-La Roche Ltd.”, Switzerland) to its biosimilar (Acellbia®, “BIOCAD”, Russia) by non-medical reasons in rheumatoid arthritis patients. Subjects and methods . 40 rheumatoid arthritis patients on basic therapy who had taken at least one course of original rituximab (MabThera®) 1000 mg twice in 2 weeks more than 6 months ago were included. They were switched to equal-dose biosimilar (Acellbia®) by non-medical reasons and were observed throughout the year. At 12, 24 weeks and one year after switching dynamics of the next parameters were evaluated: pain level according to visual analogue scale (VAS), tender joint count (TJC), swollen joint count (SJC), acute inflammatory and immunological markers, disease activity score (DAS28) calculated using erythrocyte sedimentation rate (DAS28-ESR) or C-reactive protein (DAS28-CRP), health assessment questionnaire (HAQ) index and safety profile. Results . All the data are presented as median of indicator in the moment of measurement after switching therapy (Meperiod). In 12-week period TJC [(Me]_0=9.50, Me_12=6.0, p&lt; 0.01) and SJC (Me_0=2,0, Me_12=1,0, p&lt;0.01) were decreased with positive dynamics on the 24 and 48 weeks. Also, similar results were observed in the VAS pain level. DAS28 showed significant decreasing during observation: Me0=4.38, Me24=3.55, Meyear=3.49, p&lt;0.01 for DAS28-ESR; and Me0=3.91, Me24=3.15, Meyear=3.03, p&lt;0.01 for DAS28-CRP. Immunological markers were increased or stable during the first months after switching, but then they were significantly decreased: Me0=45.0 U/ml, Meyear=23.0 U/ml, p&lt;0.01 for rheumatoid factor; and Me0=88.0 U/ml, Meyear=50.5 U/ml, p&lt;0.01 for anti-cyclic citrullinated peptide. HAQ index was stabilized during 1 year: Me0=1.00, Meyear=0.75, p&lt;0.01. Severe infusion reactions on Acellbia® were not observed, safety profile was similar to MabThera®. Conclusion . Our investigation revealed that non-medical switching from original rituximab (MabThera®, “F. Hoffmann-La Roche Ltd.”, Switzerland) to its biosimilar (Acellbia®, “BIOCAD”, Russia) has no significant influence on the therapy efficacy and safety.

Practice of Childhood Nephrotic Syndrome Management amongPediatric Nephrologists in the GCC Countries

Childhood nephrotic syndrome (NS) management is greatly variable among pediatric nephrologists worldwide. We aimed to evaluate if this variability exists among pediatric nephrologists in the gulf countries and whether certain training programs influence this variability. A web-based multiple-choice survey of 35 NS management questions distributed to certified pediatric nephrologists working in the Gulf countries. Amongst 92 invitees, the response rate was 67%. The majority (73%) were older than 50 years and male (58%). Sixty percent trained in North America and 41% had >10 years of experience. Sixty-three percent use a 12- week corticosteroids regimen for the initial treatment of childhood NS and only 10% never consider long-term small alternate dose corticosteroids therapy to sustain remission before commencing a corticosteroids-sparing agent for frequently relapsing or corticosteroids-dependent NS. Mycophenolate mofetil was the drug of choice for frequently relapsing and corticosteroids dependent NS in 51% and 58% of the participants, respectively, whereas calcineurin inhibitors were preferred by the vast majority (95%) of the participants for corticosteroids-resistant childhood NS. Regarding rituximab treatment, almost half of the participants (48%) give two doses of rituximab one to two weeks apart and 61% do not give another course of rituximab until the child relapse. Fellowship training site and the duration of the clinical experience did not seem to influence certain management of childhood NS. As shown in North American studies, great variability in the management of childhood NS does exist in the Gulf countries. The country of fellowship training and the experience did not seem to contribute to this variability.

Randomized clinical trial to compare efficacy and safety of repeated courses of rituximab to single-course rituximab followed by maintenance mycophenolate-mofetil in children with steroid dependent nephrotic syndrome

BackgroundApproximately 30% of children with idiopathic nephrotic syndrome develop a complicated course with frequent relapses or steroid dependency. Rituximab, a B cell depleting monoclonal antibody, is a safe and effective alternative to steroids or other immunosuppressants for achieving and maintaining remission in this population at short term. Despite the good initial response relapses inevitably occur after regeneration of B lymphocytes, necessitating either repeat courses of rituximab or addition of another steroid-sparing immunosuppressant.MethodsThis is a prospective, single-center, open-label, two-parallel-arm randomized controlled phase III study among children with steroid dependent nephrotic syndrome who are maintained in remission with oral steroids. One hundred children will be randomized to either Rituximab and maintenance Mycophenolate mofetil (A) or repeated courses of prophylactic Rituximab only (B). In arm A, mycophenolate mofetil (1200 mg/m2 per day) will be started 3 months after Rituximab administration. In arm B, Rituximab infusions will be administered at 0, 8 and 16 months if B cell count normalize at the given time points. Prednisolone will be discontinued in both groups 2 weeks following first course of rituximab. Primary aim is to evaluate the difference in 24-month relapse-free survival. Main secondary endpoints are cumulative prednisolone dose, frequency of relapses and changes in anthropometry. Circulating B lymphocyte populations will be studied as biomarkers or predictors of rituximab responsiveness and adverse events will be analysed.DiscussionThe study will provide evidence as to the comparative safety and efficacy of two alternative steroid-sparing therapeutic options in children suffering from steroid dependent nephrotic syndrome. The two-year study design will address the long-term results obtained with the alternative treatment protocols.Trial registrationThis trial was prospectively registered to the Clinicaltrial.gov (NCT03899103 dated 02/04/2019; https://clinicaltrials.gov/) and Clinical Trials Registry of India (CTRI/2019/04/018517 dated 09/04/2019).

Long-term maintenance rituximab for ANCA-associated vasculitis:relapse and infection prediction models.

ObjectivesFollowing a maintenance course of rituximab (RTX) for ANCA-associated vasculitis (AAV), relapses occur on cessation of therapy, and further dosing is considered. This study aimed to develop relapse and infection risk prediction models to help guide decision making regarding extended RTX maintenance therapy.MethodsPatients with a diagnosis of AAV who received 4–8 grams of RTX as maintenance treatment between 2002 and 2018 were included. Both induction and maintenance doses were included; most patients received standard departmental protocol consisting of 2× 1000 mg 2 weeks apart, followed by 1000 mg every 6 months for 2 years. Patients who continued on repeat RTX dosing long-term were excluded. Separate risk prediction models were derived for the outcomes of relapse and infection.ResultsA total of 147 patients were included in this study with a median follow-up of 63 months [interquartile range (IQR): 34–93]. Relapse: At time of last RTX, the model comprised seven predictors, with a corresponding C-index of 0.54. Discrimination between individuals using this model was not possible; however, discrimination could be achieved by grouping patients into low- and high-risk groups. When the model was applied 12 months post last RTX, the ability to discriminate relapse risk between individuals improved (C-index 0.65), and once again, clear discrimination was observed between patients from low- and high-risk groups. Infection: At time of last RTX, five predictors were retained in the model. The C-index was 0.64 allowing discrimination between low and high risk of infection groups. At 12 months post RTX, the C-index for the model was 0.63. Again, clear separation of patients from two risk groups was observed.ConclusionWhile our models had insufficient power to discriminate risk between individual patients they were able to assign patients into risk groups for both relapse and infection. The ability to identify risk groups may help in decisions regarding the potential benefit of ongoing RTX treatment. However, we caution the use of these prediction models until prospective multi-centre validation studies have been performed.

Benefits of Prophylactic Short-Course Immune Tolerance Induction in Patients With Infantile Pompe Disease: Demonstration of Long-Term Safety and Efficacy in an Expanded Cohort.

Immune tolerance induction (ITI) with a short-course of rituximab, methotrexate, and/or IVIG in the enzyme replacement therapy (ERT)-naïve setting has prolonged survival and improved clinical outcomes in patients with infantile Pompe disease (IPD) lacking endogenous acid-alpha glucosidase (GAA), known as cross-reactive immunologic material (CRIM)-negative. In the context of cancer therapy, rituximab administration results in sustained B-cell depletion in 83% of patients for up to 26–39 weeks with B-cell reconstitution beginning at approximately 26 weeks post-treatment. The impact of rituximab on serum immunoglobulin levels is not well studied, available data suggest that rituximab can cause persistently low immunoglobulin levels and adversely impact vaccine responses. Data on a cohort of IPD patients who received a short-course of ITI with rituximab, methotrexate, and IVIG in the ERT-naïve setting and had ≥6 months of follow-up were retrospectively studied. B-cell quantitation, ANC, AST, ALT, immunization history, and vaccine titers after B-cell reconstitution were reviewed. Data were collected for 34 IPD patients (25 CRIM-negative and 9 CRIM-positive) with a median age at ERT initiation of 3.5 months (0.1–11.0 months). B-cell reconstitution, as measured by normalization of CD19%, was seen in all patients (n = 33) at a median time of 17 weeks range (11–55 weeks) post-rituximab. All maintained normal CD19% with the longest follow-up being 248 weeks post-rituximab. 30/34 (88%) maintained negative/low anti-rhGAA antibody titers, even with complete B-cell reconstitution. Infections during immunosuppression were reported in five CRIM-negative IPD patients, all resolved satisfactorily on antibiotics. There were no serious sequelae or deaths. Of the 31 evaluable patients, 27 were up to date on age-appropriate immunizations. Vaccine titers were available for 12 patients after B-cell reconstitution and adequate humoral response was observed in all except an inadequate response to the Pneumococcal vaccine (n = 2). These data show the benefits of short-course prophylactic ITI in IPD both in terms of safety and efficacy. Data presented here are from the youngest cohort of patients treated with rituximab and expands the evidence of its safety in the pediatric population.

Rituximab and immune thrombocytopenia in adults: The state of knowledge 20 years later

Rituximab has been used for immune thrombocytopenia (ITP) for almost 20 years and is now considered a valid off-label second-line treatment. About 60% to 70% of patients with ITP show initial response to rituximab, but in half of these patients, the disease will eventually relapse. Therefore, in 30% of patients with persistent or chronic ITP, one course of rituximab at 375 mg/m2/week for 4 weeks or 2 fixed 1000-mg rituximab infusions allows for a sustained response rate at 5 years. Unfortunately, to date, no robust predictor of long-term sustained response has been found to assist the physician in deciding to treat with rituximab on an individual basis, and the choice of rituximab or another second-line treatment must be individualized and shared with the patient. Retreatment with rituximab has been found efficient, with a similar or higher magnitude and duration of response in most patients. Rituximab is usually well tolerated, with mainly mild and easily manageable infusion-related adverse events. Severe infections are uncommon, including in the long-term, and occur in patients with at least another contributing factor in more than two thirds. Several issues remain to be resolved. Indeed, head-to-head comparisons with other and new treatments in ITP and robust predictors of long-term response are urgently needed to better determine the position of rituximab in the therapeutic armamentarium for adult ITP. Additionally, the place of combination therapies, maintenance therapy with rituximab and rituximab in newly-diagnosed ITP deserve additional studies.

Long-term outcomes of rituximab therapy in pemphigus.

Rituximab induces a rapid remission in most patients with pemphigus. Our aim was to assess the long-term efficacy of rituximab in this disease. We conducted a retrospective study of 59 patients with pemphigus treated with rituximab and observed over a median period of 104months. The rate of complete remission off therapy (CRoff) after the first rituximab cycle was 39%, increasing to 61% with additional rituximab courses. Long-term CRoff was achieved in 27% of patients. The recurrence rate after the first rituximab cycle was 63%, decreasing to approximately 40% with subsequent rituximab cycles. Median time to relapse after the first and subsequent rituximab cycles was 25months. Renewed rituximab therapy reinduced complete remission in 94% of cases. Baseline anti-desmoglein antibody levels of ≤250U/mL were significantly associated with the outcome of CRoff. In paired serum samples obtained before the first and six months after the last rituximab therapy, significant reductions of desmoglein-specific autoantibodies were observed. Patients relapsing after a complete remission induced by the first rituximab cycle were more likely to achieve CRoff than patients relapsing after a less favourable outcome and non-responders. There was no significant difference in age, sex, pemphigus subtype, rituximab dosing and disease duration between patients achieving CRoff and those not meeting this end point. Lower desmoglein-specific antibody levels at baseline were predictive of CRoff. In patients receiving multiple rituximab cycles, complete remission after the first cycle was associated with a favourable long-term outcome. Repeated rituximab courses were highly effective for relapsed disease and improved the overall outcome.

Treatment of fibrillary glomerulonephritis with rituximab: a 12-month pilot study.

Fibrillary glomerulonephritis (FGN) is a rare type of glomerulonephritis with poor prognosis, with no known effective therapies available for treatment. The objective of the study was to evaluate the efficacy and safety of rituximab in treatment of patients with FGN and to investigate the effect of rituximab on DNAJB9 levels. This was a pilot prospective clinical trial in which patients with idiopathic FGN were treated with two courses of rituximab (1 g each) 2 weeks apart at the beginning and then again at 6 months. Primary outcome was defined as preservation of kidney function at 12 months with stable or increased creatinine clearance. Secondary outcome was defined as achieving complete remission (CR) defined as proteinuria <300 mg/24 h or partial remission (PR) with proteinuria <3 g/24 h and at least 50% reduction in the proteinuria. DNAJB9 levels were also measured in the serum at baseline, 6 and 12 months. The creatinine clearance did not change significantly during this time, from 47.7 mL/min/1.73 m2 at baseline to 43.7 mL/min/1.73 m2 during follow-up (P = 0.15). Proteinuria declined from 4.43 (1.6-5.53) g/24 h at baseline to 1.9 (0.46-5.26) g/24 h at 12 months but did not reach significance (P = 0.06). None of the patients reached CR, and 3 of the 11 achieved PR. There was no change in the DNAJB9 levels following treatment with rituximab. The most common adverse event was nasal congestion, fatigue and muscle cramps. Treatment of patients with two courses of rituximab over a span of 6 months was associated with stabilization of renal function but did not result in a significant change in proteinuria and with no change in the DNAJB9 levels.

Development of diffuse large B-cell lymphoma after sofosbuvir-ledipasvir treatment for chronic hepatitis C: A case report and literature review.

Recently, treatments for chronic hepatitis C virus (HCV) infection have significantly improved by the development of direct-acting antiviral agents (DAAs) and almost all patients with HCV can complete antiviral treatment without apparent adverse events. Malignant lymphoma, particularly B-cell non-Hodgkin's lymphoma, is one of the extrahepatic manifestations associated with chronic HCV infection. The effectiveness of anti-HCV therapy with DAAs for B-cell non-Hodgkin's lymphoma has been demonstrated in recent reports, whereas late-onset B-cell non-Hodgkin's lymphoma after HCV eradication with DAAs has occasionally been reported. In the present study, a 77-year-old man with chronic hepatitis C and intermediate liver cancer risk received sofosbuvir-ledipasvir treatment for 12 weeks. Two months following the end of antiviral therapy, he had achieved sustained virologic response for 8 weeks. However, the patient occasionally found swelling of the right cervical lymph nodes without any subjective symptoms. Lymph node biopsy revealed diffuse large B-cell lymphoma and whole-body 18F-fluorodeoxyglucose (FDG) positron emission tomography with computed tomography showed increased FDG uptake in the right cervical, right submandibular, mediastinal and mesenteric lymph nodes. The patient received six courses of rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone chemotherapy and achieved complete response at 8 months after chemotherapy initiation. Thus, the development of lymphoid malignancies may arise, even after HCV eradication with DAAs. Therefore, clinicians should be aware of such risks during and after antiviral treatment with DAAs.

Implication of baseline levels and early changes of C-reactive protein for subsequent clinical outcomes of patients with rheumatoid arthritis treated with tocilizumab

BackgroundRheumatoid arthritis (RA) is characterised by clinical joint swelling and elevation of acute phase reactant levels, typically measured by the C-reactive protein (CRP). Clinical and inflammatory responses are usually concordant,...

P0374TREATMENT EFFICACY OF BIOSIMILAR RITUXIMAB (TRUXIMA) COMPARED TO THE ORIGINATOR (MABTHERA) IN PATIENTS WITH ANCA ASSOCIATED VASCULITIS

Abstract Background and Aims Truxima is a biosimilar version of rituximab. It was licensed &amp; launched in the United Kingdom in April 2017. A biosimilar medicine is made to be highly similar in quality, safety and efficacy to existing licensed “reference” biological medicine and the cost is often significantly lower. A recent systematic review showed comparable long-term efficacy and safety of biosimilar rituximab to the originator drug in treatment of rheumatoid arthritis and non-hodgkin’s lymphoma. Fewer data are available in regards to the efficacy of biosimilar rituximab in treatment of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). A retrospective study was thus conducted in our centre to examine the efficacy of Truxima when compared to the reference rituximab (MabThera) in the treatment of patients with AAV. Method All patients with new or relapsing AAV who received first ever rituximab therapy between 1/1/2016 and 31/12/2018 were identified via hospital dispensing database. Patients were stratified into Truxima or MabThera treatment group depending on the version of rituximab administered. Primary outcomes that were assessed include: time to B cell depletion (defined as absolute B cell count (ABC) ≤10) and repletion (i.e ABC &amp;gt;10 and &amp;gt;20); time to antimyeloperoxidase(MPO)/antiproteinase 3(PR3)-ANCA negativity; Secondary outcomes assessed include: overall survival, time to major relapse (defined as relapse requiring further course of rituximab for remission induction); adverse events including episodes of neutropenia, hypogammaglobulinemia and major infusion reactions. Subgroup analysis in patients who received concomitant cyclophosphamide and rituximab or other induction therapy was performed to examine if it impacts on the treatment efficacy. Results 59 and 60 patients received Truxima and MabThera respectively for treatment of new or relapsing AAV. The baseline characteristic (age, gender, entry estimated Glomerular Filtration Rate, proportion of patients received concomitant cyclophosphamide, ANCA serology and organ involvement) of both group were comparable. All patients achieved clinical remission following induction treatment. Using Kaplan Meier analysis and log rank test, no difference was identified in time to B cell depletion or repletion (Figure 1&amp;2), MPO/PR3-ANCA negativity (Figure 3), overall survival or major relapses requiring further rituximab as induction therapy. Treatment efficacy of Truxima and MabThera did not differ in subgroup analysis. However we observed that patients who received concurrent cyclophosphamide during induction therapy achieved MPO/PR3-ANCA negativity more rapidly compared to those who did not irrespective of the version of rituximab received. No difference in adverse events such as major infusion reactions was seen in either group upon first rituximab exposure. Two patients in each group developed reactions following repeated dosing of rituximab. Conclusion Biosimilar rituximab Truxima appears to have comparable treatment efficacy compared to the reference drug in our cohort of patients with AAV.

P0346THE EFFECTS OF RITUXIMAB MAINTENANCE THERAPY ON LUPUS NEPHRITIS

Abstract Background and Aims Lupus Nephritis (LN) is the organ manifestation with the most severe prognosis in Systemic Lupus Erythematosus (SLE). Treatment options are limited due to partial efficacy, intolerance or side effects; moreover 10% of patients reach ESRD despite treatments. Rituximab (RTX) in LN is recommended as second line drug for induction of the remission after failure of Cyclophosphimide or Mycophenolate Mofetil. We have shown a role for RTX as maintenance therapy (RMT) in SLE however the effects of such approach on LN are still unclear. Aim of this study was a sub-analyses of a cohort of SLE patients treated with RTX focusing on the ones with active LN at the moment of the first RTX administration. Methods Patients with active LN at the time of the first RTX administration within a cohort of 147 patients with SLE were identified. Patients with SLE and a flare of LN were classified as treated with a “Single RTX course” (any RTX regimen administered within a single month) (SRC) or with RMT. Patients receiving at least three SRCs with the aim of relapse prevention and within 4 to 8 months between consecutive treatments, were classified as receiving RMT. LN activity was determined according to creatinine, proteinuria and haematuria; complete response (CR) was defined as a decrease of proteinuria to &amp;lt;0.5 g/day, normal creatinine and negative urinary sediment; partial response (PR) was defined as ≥50% improvement in creatinine and proteinuria, treatment failure (TF) was any other condition. A renal flare (RF) was defined as an increase of creatinine and/or proteinuria &amp;gt;30% or the detection of an active urinary sediment due, according to the treating physician, to active disease. Results 33 patients were identified; a renal biopsy had been performed in 76% with prevalence of class IV lupus nephritis in 16/33 (48%). Six months after RTX the rate of CR, PR and TF was respectively 36%, 27% and 36%; proteinuria and the prednisolone dose reduced significantly compared to baseline (respectively from a median of 2200 mg/day (IQR 499-5400) to 850 mg/day (IQR 400-1700) (p=0.005)) and from 25 mg (IQR 11-25) to 10 mg (IQR 6.125-15) (p&amp;lt;0.0001)). At univariate analyses the only factor associate to the risk of TF was a high number of immunosuppressive drugs employed before RTX (p=0.0077). Of the 33 patients, 11 received RMT with a median duration of 18 months (IQR 12,6-23,4) and a median RTX dose of 5 g (IQR 4-6). During the RMT 3 patients experienced a renal flare. The median follow-up after the last RTX administration within the SRC and the RMT groups was respectively 15 months (IQR 13,5-18,4) and 16 months (IQR 3,5-23). Comparing the RF free-survival of the two subgroups after the last RTX infusion, there was a trend towards a longer relapse free survival after the RMT (p=0.057) (figure, left panel). Of interest, the renal relapse free-survival of the 11 patients treated with RMT after the last RTX infusion was significantly longer compared to the one of the same group after the first RTX (p=0.0271) (figure, right panel). The incidence of SAEs per 100 patient years was 0.31 in the SRC group and 0.74 in the RMT group. Conclusion RTX is confirmed as an effective option for patients with LN. A RMT may have a role in improving LN disease control compared to a single RTX administration.

Evaluation of efficacy and safety of rituximab in combination with mycophenolate mofetil in patients with nonspecific interstitial pneumonia non-responding to a first-line immunosuppressive treatment (EVER-ILD): A double-blind placebo-controlled randomized trial

IntroductionNonspecific interstitial pneumonia (NSIP) are rare but severe diseases, with high mortality and morbidity, with no effective pharmacological treatment allowing for long-term remission, and therefore no clear therapeutic recommendations. Classic immunosuppressants are used as first-line treatment, with only one third of patients being responders and no clear recommendations exist for the choice of the second-line therapy. The EvER-ILD study is the first one to prospectively evaluate the efficacy and safety of rituximab and mycophenolate mofetil (MMF) versus placebo and MMF in a broad range of NSIP patients that did not respond to a first-line therapy. A pharmacokinetic-pharmacodynamic analysis based on rituximab serum concentrations will allow identification of potential factors associated with therapeutic response and/or adverse effects. MethodsEvER-ILD study is a French multicenter, prospective, randomized, double blind, placebo-controlled, superiority trial. Patients with severe and progressive NSIP non-responding to a first line immunosuppressive treatment will be randomized in 2 groups of treatment: one course of rituximab plus 6 months MMF (RTX-MMF group) and one course of placebo plus 6 months MMF (Placebo-MMF group). The primary outcome is the change in Forced Vital Capacity (FVC, % of predicted) from baseline to 6 months. Several clinical, biological, and quality of life secondary outcomes will be measured at 3, 6 and 12 months. A sample size of 122 patients (61 patients per group) would allow to show a point difference between groups in the change of FVC at 6 months, based on a common standard deviation for FVC change of 8% with a power of 90%, alpha 5% two-sided, and anticipating an extreme 10% drop-out rate. Ethics and disseminationThe protocol was approved by the French Research Ethics Committee (CPP Tours Ouest 1 2016-R28) on November 10, 2016, and by the French competent authority (ANSM, reference 160771A-22) on December 1st, 2016. This article refers to protocol V2, dated November 18, 2016. An independent data safety monitoring board will review safety and tolerability data for the duration of the trial. Results will be disseminated via peer reviewed publication and presentation at international conferences. Trial registration numberNCT02990286 (clinicaltrials.gov), EudraCT 2016-003026-16 (European Medicines agency).