Second Course Of Rituximab Research Articles

Long-Term Efficacy and Safety of Rituximab Versus Tacrolimus in Children With Steroid Dependent Nephrotic Syndrome

In the Rituximab for Relapse Prevention in Nephrotic Syndrome (RITURNS) trial, we demonstrated superior efficacy of single-course rituximab over maintenance tacrolimus in preventing relapses in children with steroid dependent nephrotic syndrome (SDNS) during a 1-year observation. Here we present the long-term outcomes of all 117 trial completers, who were followed up for another 2 years. Relapsing patients in the rituximab arm received a second course of rituximab, either with (n= 44) or without mycophenolate mofetil (MMF) cotreatment (n= 15). In the tacrolimus arm, second line rituximab monotherapy was initiated after relapses (n= 32) or electively (n= 24). All 12-month relapse-free patients in the rituximab arm relapsed in the second postexposure year, resulting in similar median relapse-free survival times in the 2 trial arms (62 vs. 59 weeks). Second line rituximab in the tacrolimus arm was less effective than first-line therapy in patients switched to rituximab following a relapse (relapse-free survival 55 vs. 63 weeks, P< 0.01). B-cell counts 6 months post-rituximab predicted relapse risk both for first and second line therapy. MMF cotreatment yielded much improved 2-year relapse-free survival as compared to rituximab monotherapy (67% vs. 9%, P< 0.0001). Higher grade 2 adverse event rates were observed post-rituximab versus on tacrolimus (0.87 vs. 0.53 per year). The superior therapeutic effect of rituximab in SDNS vanishes during the second year post-exposure. Rituximab appears to yield longer remission when applied as first line as compared to second line therapy. Maintenance MMF following rituximab induces long-term disease remission.

A case of neuromyelitis optica spectrum disorder (NMOSD) and acute myositis following SARS-CoV-2 infection

Background and aims: Neurological manifestations of COVID-19 have been described. We report a case of seropositive NMOSD and acute myositis following SARS-CoV-2 infection. Methods: A previous healthy 35-years old man was admitted for NORB, a month after paucisymptomatic SARS-CoV-2 infection. Nasopharyngeal tests for SARS-CoV-2 was negative and serological IgG and IgM were positive. The neurological examination showed left eye blindness and myalgia. Blood examination showed elevated CK (>1000 UI/l), positive ANA (1:640) and anti-TPO (>1300 U/ml). Brain MRI showed T2/FLAIR left optic nerve hyperintensity with contrast enhancement. The EMG revealed signs of acute myogenic damage. He received intravenous methylprednisolone with poor recovery on vison but full recovery on muscle symptoms. Four months later he present NORB in contralateral eye;MRI showed optic chiasm hyperintensity, serum anti-AQP-4-antibodies were positive, EMG and CK were normalized. The patient received intravenous steroids and Immunoglobulins and started rituximab. Nevertheless, three months later he developed the area postrema syndrome, he was retreated with intravenous steroids and immunoglobulins and achieved a complete recovery. In March 2021, he underwent the second course of rituximab with clinical and radiological stability. Results: The patient was diagnosed with seropositive NMOSD, presented with recurrent NORB and area postrema syndrome, associated to acute myositis and autoimmune tiroiditis after SARS-CoV-2 infection. Conclusions: We supposed that SARS-CoV-2 may cause a post-infectious autoimmune response directed against AQP4 and other target (the muscle, the tiroid gland). Post-infectious autoimmunity is a potential mechanism in a subset of patients with COVID-19-related neurologic disease. Further research is needed to clarify this association.

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.

Post Allograft Rituximab Responsive Cytopenia (RRC)

Background: Cytopenia post allograft can be multi-factorial. Known causes include viral infection, septicaemia, graft versus host disease (GVHD), nutritional deficiency, myelotoxic drugs, relapsed malignancy but immune mediated cases are increasingly observed. There remains a group of cases where no obvious cause is identified. The incidence of this complication is small but may be underestimated and treatment options and results are not defined. Aim: This single centre analysis retrospectively evaluated cases of post-transplant cytopenia presumed to be immune mediated or with no obvious cause and response to antiCD20 antibody (Rituximab) therapy. Study period was 2012 to 2019. Data was collected from electronic patient records, case notes and haematology data base. Results: From 2012 to 2019, 988 patients received allograft (n=390) or autograft (n=598) for haematological malignancy or bone marrow failure syndrome. Twenty-four cases received Rituximab for cytopenia post allograft (24/390, 6.2%). Median age was £9yr. (range: 19-68), 19 were males (79.2%) and allograft were done for severe aplastic anaemia (n=4), Ac. Leukaemia (n=6), Hodgkins disease (n=4), non-Hodgkins lymphoma (n=4), MPD/MDS (n=5) and myeloma (n=1). Conditioning was reduced intensity in n22 case, myeloablative in 2 cases and included campath (n=18) or ATG (n=2) in 20 cases (83.3%). Donor was sibling (n=6) or unrelated (n=22) and 23 (96%) patients received PBSC. All allografts were donor/patient CMV matched (NN: 15, PP: 9). Rituximab was used at a median of 171 days post transplant (range: 55-6174). Cytopenia was trilineage in 8, bilineage in 10 and single lineage in 6 cases. Median haematological parameters were as follows: Hb 78gm/L (68-152), WBC: 2x109/L (0-12), Platelets 28x109/L (4-638). DCT was positive in 7 of the 15 cases where results were available. Seventeen of the 22 cases who had bone marrow evaluation showed hypocellular marrow with no malignancy (3 had normocellular marrow) . Seven of the 10 cases where reticulocyte count pre-rituximab was available, showed response above 2% . Cytopenia was not related to infection, viruses, it B12 or folate deficiency. Response to rituximab therapy was defined as CR (normal counts, transfusion independence, no treatment with steroids or G-CSF), Stable (improvement in counts with platelets&gt;50, Hb&gt;100 and ANC&gt;1.0 without support) or no response. Rituximab was delivered weekly in the dose of 375mg/m2 for 4 weeks. Twelve patients achieved complete response (50%), 3 achieved stabilization (12.5%) and 9 did not show any response (37%) for overall response rate of 63%. All patients with positive DCT responded to Rituximab (7/7, 100%) but even in negative DCT group 4 responded (4/8, 50%). Response was 100% in single lineage cytopenia (6/6), 40% in bilineage cytopenia (4/10) and 63% in trilineage cytopenia (5/8) [p=0.052]. Three patients received second course of Rituximab for recurrence of cytopenia and all achieved second complete response (all three had autoimmune haemolysis). Numbers are too small to identify the predictors but there was trend towards better outcome in patients younger than 40 yrs. age (10/12 vs. 5/12, p=0.035) and patients with Hodgkins disease (4/4 vs. 11/20, p=0.09) but there was no effect of gender, intensity of conditioning, use of campath/ATG or CMV status. Treatment was well tolerated and infusion reactions were uncommon. We identify that the main drawback of this analysis is substantial amount of missing data, especially haematological investigations that precludes identification of predictors or trends. Conclusion: Rituximab should be considered as an option for management of post allograft cytopenia with immune aetiology or with no identified cause. Response rate is substantial and the benefit is sustained. It will be useful to have larger cohort of cases to identify the predictors of response. Disclosures Kulkarni: Therakos, Clegene: Honoraria. Murray:Therakos: Honoraria. Castleton:Novartis, Pfizer, Amgen: Consultancy, Honoraria. Cavet:AMGEN, Autolus, Celgene, EUSA, Jansen/J&amp;J, Novartis,: Consultancy, Honoraria, Research Funding, Speakers Bureau. Wiseman:Novartis, Celgene: Consultancy, Honoraria. Somervaille:Novartis: Consultancy. Sommerfeld:Gilead: Other: Educational grant. Bloor:Abvie, Gilead, Novartis, Autolus, Celgene, etc: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Educational grant.

Rituximab for non-responsive idiopathic membranous nephropathy in a Chinese cohort.

Rituximab had been shown to be effective in inducing remission of nephrotic syndrome in patients with idiopathic membranous nephropathy (iMN). This study applied rituximab therapy for 36 non-responsive iMN patients to investigate its effects and safety. Thirty-six iMN patients who were non-responsive to prior immunosuppression were enrolled. Rituximab was used for B-cell depletion in patients, with a goal of <5 B cells/mm3 in the circulation. After completing the study, patients were monitored for a median of 12.0 months [interquartile range (IQR) 9.0-19.3]. Fifteen of the 36 (41.7%) patients achieved partial (n = 13) or complete (n = 2) response to the rituximab treatment. The median time for achieving partial response was 4.0 months (IQR 3.0-6.0). The responders had relatively lower levels (118 ± 112 U/mL versus 345 ± 357 U/mL, P = 0.03) of anti-phospholipase 2 receptor (PLA2R) antibodies before the rituximab treatment, and all of them achieved antibody depletion or reduction. B-cell depletion was achieved in all patients. Renal function remained stable in the responders [estimated glomerular filtration rate (eGFR) 53.3 ± 40.5 versus 55.6 ± 33.2 mL/min/1.73m2, P = 0.67] but deteriorated in the non-responders (eGFR 57.5 ± 29.3 versus 45.3 ± 32.8 mL/min/1.73m2, P = 0.02) with two patients reaching end-stage kidney disease. Two of the 15 patients relapsed during the follow-up period with anti-PLA2R antibody reoccurrence and B-cell reconstitution. The second course of rituximab combined with tacrolimus induced a faster partial response again in one patient. Rituximab therapy could induce remission of proteinuria and stabilization of renal function in non-responsive iMN patients, even those with damaged renal function. Anti-PLA2R antibodies may be used as a marker for individualized rituximab dosage and treatment monitoring.

Mycophenolate Mofetil Following Rituximab in Children With Steroid-Resistant Nephrotic Syndrome.

Rituximab is being increasingly used in children with idiopathic nephrotic syndrome resistant to standard treatments. In spite of good initial response, rituximab responders always remain prone to further relapse, necessitating either repeat course of rituximab or addition of another steroid-sparing immunosuppressant. A retrospective analysis of baseline clinico-pathologic presentation and treatment outcome (complete remission, partial remission, or no response) was performed among 24 children with refractory-idiopathic SRNS over a follow-up period of 24 months. Children received 2 to 4 rituximab infusions (375 mg/m(2) weekly) depending on circulating B-cell level. At 3-month follow-up, a second course of rituximab was administered (if >5 B cells/mm(3)) along with MMF (1200 mg/m(2) per day) maintenance therapy. Of 24 patients, 54% (13/24) and 46% (11/24) had minimal change disease and focal segmental glomerulosclerosis, respectively, on renal histopathology. After the first course of rituximab, 21% (5/24) of children achieved complete remission; however, most (4/5) of them relapsed again at a median interval of 53 (interquartile range 46-72) days. Depending on response to the first course of rituximab, MMF was started on 15 children at 3 months. After 6 months, 67% (10/15) of children on MMF achieved complete remission and 33% (5/15) remained at partial remission. At 24 months overall, 25% (6/24) and 42% (10/24) of children were in complete remission and partial remission, respectively; 33% (5/15) of children continued sustained complete remission after postrituximab-MMF maintenance therapy in comparison with no sustained complete remission with rituximab alone at 24 months (P < .001). MMF may be an effective and safe maintenance therapy to consider as an additive immunosuppressant after induction with rituximab in maintaining remission among children with refractory SRNS.

What is a reflex? A guide for understanding disorders of consciousness.

Uncertainty in diagnosing disorders of consciousness, and specifically in determining whether consciousness has been lost or retained, poses challenging scientific and ethical questions. Recent neuroimaging-based tests for consciousness have cast doubt on the reliability of behavioral criteria in assessing states of consciousness and generate new questions about the assumptions used in formulating coherent diagnostic criteria. The reflex, a foundational diagnostic tool, offers unique insight into these disorders; behaviors produced by unconscious patients are thought to be purely reflexive, whereas those produced by conscious patients can be volitional. Further investigation, however, reveals that reflexes cannot be reliably distinguished from conscious behaviors on the basis of any generalizable empirical characteristics. Ambiguity between reflexive and conscious behaviors undermines the capacity of the reflex to distinguish between disorders of consciousness and has implications for how these disorders should be conceptualized in future diagnostic criteria.

Use of rituximab maintenance infusions in relapsing responders with ITP and AIHA

Background: Rituximab is an often effective treatment of ITP (Immune thrombocytopenia). However treated patients who respond often relapse. While they may have an almost identical response to retreatment, this includes relapsing again in the same time frame (Hasan, AmJHem, 2009). To evaluate the efficacy of rituximab maintenance in ITP patients responding to but relapsing after Rituximab. Methods: Sixteen relapsed patients were infused with 6 single infusions of 4monthly or other additional rituximab over 2 years following a 2nd 4-infusion course of rituximab. The duration of their response was compared to their response to their first course of rituximab. Results: Of 16 eligible patients, 9 had AHA, 7 ITP. All patients responded to their second 4-infusion course of rituximab. 7 patients finished the 6 maintenance infusions; 5/7 are still maintaining their remission for a median of 44 months following the 2 cycle of rituximab. One patient received 4 courses of 4-infusions of rituximab and is maintaining remission at 35 months. Two others are either too early to assess (1) or lost to f/u (1). Two patients are receiving maintenance and in remission currently. Three received 6 infusions but are in long-term remission. One (and one of the two who relapsed after 6 maintenance infusions) no longer responds to rituximab. No important toxicity was seen. JC virus cultures were negative in several of the patients. Three patients developed hypogammaglobulinemia and needed IVIG prophylaxis against infections; one patient had bacteremia and one, pneumonia. Conclusion: Rituximab maintenance infusion achieves a much longer lasting remission than only a second course of rituximab: 9 patients are in lasting remissions many months after their last rituximab infusion. Rituximab maintenance is an effective and seemingly safe addition to standard rituximab as a therapeutic option to treat refractory ITP.

Hypersensitivity reactions to biologic disease modifying antirheumatic drugs: experience from the TTSH Singapore biologics registry

Results There were 217 patients of Asian ethnicity who had ever received a bDMARD, of whom 30 (13.8%) had received more than 1 bDMARD. These comprised rituximab (78, 35.9%), infliximab (59, 27.2%), etanercept (51, 23.5%), adalimumab (41, 18.9%), golimumab (8, 3.7%), anakinra (4, 1.8%), abatacept and tocilizumab (3, 1.4% each). HSR occurred in 4 female patients following previous exposure to an anti-tumour necrosis factor inhibitor (TNFi) (2) and rituximab (2) respectively. A 67-year-old Chinese female with rheumatoid arthritis developed fever and hypotension without rash or other organ-specific involvement, within 1 hour of the second dose of infliximab 200 mg 2 weeks later. She switched to adalimumab without adverse reaction. Another 34-year-old Malay female with psoriatic arthritis developed optic neuritis following the third dose of adalimumab 40 mg every other week. She recovered and switched to abatacept without adverse reaction. A 28-year-old female with systemic lupus erythematosus (SLE) developed acute urticaria following the second dose of the third course of rituximab 500 mg given 2 weeks apart. Another 27-year old female with SLE developed anaphylaxis with flushing, facial angioedema, dyspnoea and wheeze, following the second dose of the second course of rituximab 500 mg 5 years later. None of the patients with immediate reactions to infliximab/ rituximab agreed to have diagnostic skin testing in view of costs. The patient with anaphylaxis declined desensitization to rituximab. There were no HSR to any of the other bDMARDs. Exposure to more than 1 bDMARD within/across different classes did not increase the risk of HSR. There were no deaths from HSR.

Rituximab for minimal-change nephrotic syndrome in adulthood: predictive factors for response, long-term outcomes and tolerance.

Minimal-change nephrotic syndrome (MCNS) is a common cause of steroid sensitive nephrotic syndrome (NS) with frequent relapse. Although steroids and calcineurin inhibitors (CNIs) are the cornerstone treatments, the use of rituximab (RTX), a monoclonal antibody targeting B cells, is an efficient and safe alternative in childhood. Because data from adults remain sparse, we conducted a large retrospective and multicentric study that included 41 adults with MCNS and receiving RTX. Complete (NS remission and withdrawal of all immunosuppressants) and partial (NS remission and withdrawal of at least one immunosuppressants) clinical responses were obtained for 25 and 7 patients, respectively (overall response 78%), including 3 patients that only received RTX and had a complete clinical response. After a follow-up time of 39 months (6-71), relapses occurred in 18 responder patients [56%, median time 18 months (3-36)]. Seventeen of these received a second course of RTX and then had a complete (n = 13) or partial (n = 4) clinical response. From multivariate analysis, on-going mycophenolate mofetil (MMF) therapy at the time of RTX was the only predictive factor for RTX failure [HR = 0.07 95% CI (0.01-0.04), P = 0.003]. Interestingly, nine patients were still in remission at 14 months (3-36) after B-cell recovery. No significant early or late adverse event occurred after RTX therapy. RTX is safe and effective in adult patients with MCNS and could be an alternative to steroids or CNIs in patients with a long history of relapsing MCNS.

Alemtuzumab plus cyclosporine treatment of the autoimmune hemolytic anemia in an adult bowel transplant.

An adult male underwent a bowel transplant for tufting enteropathy, receiving alemtuzumab, tacrolimus, and steroids as immunosuppressants. Five years later, he developed an autoimmune hemolytic anemia (AIHA), anti-IgG positive, with reduced reticulocyte count, leukopenia, and thrombocytopenia with antiplatelet antibodies. After an unsuccessful initial treatment with high dose steroids, reduction in tacrolimus dose, and intravenous immunoglobulin (IVIG), a bone marrow biopsy revealed absence of erythroid maturation with precursor hyperplasia. The patient was switched to sirolimus and received four doses of rituximab plus two courses of plasmapheresis, which decreased his transfusion requirements. After a febrile episode one month later, the AIHA relapsed with corresponding decreases in platelet and leukocyte count: cyclosporine A (CsA) was started with a second course of rituximab and IVIG without response, even though repeat bone marrow biopsy did not reveal morphology correlated to an acquired pure red cell aplasia (APRCA). Considering the similarity in his clinical and laboratory findings to APRCA, alemtuzumab was added (three doses over a week) with CsA followed by steroids. The patient was eventually discharged transfusion-independent, with increasing hemoglobin (Hb) levels and normal platelet and leukocyte count. One year later he is still disease-free with functioning graft.

AB0626 Dynamic study of B-cells using highly sensitive flow cytometry (HSFC) in systemic lupus erythematosus patients’ receiving anti-B-cell therapy

ObjectivesDynamic study of B-cell using HSFC in systemic lupus erythematosus (SLE) patients’(pts) receiving anti-B-cell therapy with Rituximab (RTM) and definition of correlation with clinical and laboratory disease activity on the...

THU0324 Rituximab for severe disease flares in childhood ANCA vasculitides

BackgroundChildren with ANCA vasculitides frequently present with life-threatening organ manifestations including alveolar hemorrhage, critical subglottic stenosis and renal failure due to rapidly progressive glomerulonephritis (GN). The current initial management for...

Safety of Rituximab in Combination with Other Biologic Disease-modifying Antirheumatic Drugs in Rheumatoid Arthritis: An Open-label Study

To characterize the safety of rituximab (RTX) in combination with biologic disease-modifying antirheumatic drugs (DMARD) in patients with rheumatoid arthritis (RA). We did an open-label study of the safety and efficacy of RTX in adult patients with active RA and an inadequate response to ≥ 1 biologic for ≥ 12 weeks (stable dose ≥ 4 weeks). RTX (2 × 500 mg) was added to patients' current biologic and nonbiologic DMARD treatment. After 24 weeks, patients with 28-joint Disease Activity Score ≥ 2.6 were eligible for RTX retreatment. The primary endpoint was the proportion of patients developing a serious adverse event (SAE) within 24 weeks of initiating RTX. Patients (n = 176) received RTX with 18 different biologic/DMARD combinations. Adalimumab alone (n = 46; 26.1%) or etanercept alone (n = 37; 21.0%) plus RTX were the most common combinations. Overall, 90.9% and 76.1% of patients completed 24 and 48 weeks, respectively; 147 patients (83.5%) received a second course of RTX. Over 24 weeks, 9.1% of patients reported SAE (24.3 events/100 patient-yrs, 95% CI 15.5-38.1). The SAE rate was similar over 48 weeks (22.4 events/100 patient-yrs, 95% CI 15.9-31.5). Four serious infections were reported over 48 weeks (2.7 events/100 patient-yrs, 95% CI 1.0-7.2). No SAE occurred within 24 h of any RTX infusion. Efficacy responses improved numerically at Week 48 compared with Week 24. The overall safety profile of RTX in combination with 1 other biologic was consistent with that previously reported for RTX plus methotrexate or other nonbiologic DMARD. (Clinicaltrials.gov NCT00443651).

Induced psoriasis after rituximab therapy for rheumatoid arthritis: a case report and review of the literature

Rituximab is a human/murine monoclonal antibody targeting the CD20 antigen on B-lymphocytes surface. Although it has been licensed for treatment of non-Hodgkin's lymphoma, nowadays it is also a novel therapy for autoimmune diseases, such as rheumatoid arthritis and systemic lupus erythematosus. Despite the increasing evidence regarding the safety and efficacy of rituximab in these conditions, many cutaneous adverse events have been reported. Here, we describe the case of a 69-year-old patient, affected by rheumatoid arthritis, who developed psoriatic lesions on her trunk and arms, three months after the second course of rituximab. Similar cases appearing in the literature will also be briefly mentioned.

A case of ITP that'll make you go blue in the face

Immune Thrombocytopenia Purpura (ITP) is a relatively common paediatric presentation (3-8 cases per 100,000). It is usually a benign condition with spontaneous resolution occurring in 80% of cases within 6 months. Chronic ITP is only rarely associated with severe symptoms and the mainstay of treatment remains supportive care. We describe an unusual case of chronic relapsing symptomatic ITP whose refractory nature challenged conventional treatment options and triggered reflection on ITP management. 3 year old AS presented acutely with fever and extensive petechiae, following a 6 month history of easy bruising. She was initially treated for meningococcaemia but a diagnosis of ITP was subsequently made based on the findings of an isolated thrombocytopenia (with an otherwise normal blood film) in the absence of hepatospenomegaly or lymphadenopathy. Initial management was conservative. However, symptomatic cutaneous and mucosal bleeding continued associated with thrombocytopenia (&lt;20−×10 9/L). Active management was therefore considered at this stage. Lymphoproliferative, autoimmune and post-viral causes were excluded and empirical treatments were given for symptom relief. Prednisolone was ineffective and intravenous immunoglobulin provided only short-lived improvement. As symptoms persisted, a second line agent rituximab was given, achieving 10 months of remission. Following further relapse, a second course of rituximab achieved remission prior to performing a laparoscopic splenectomy. Despite this she relapsed again 6 months later. Treatment options were again reviewed and oral dapsone was started. This was ineffective and stopped due to symptomatic methaemoglobinaemia (22.6%). It was subsequently restarted at a lower dose but she again developed methaemoglobinaemia and therefore dapsone was discontinued and a yellow card was completed to highlight this dramatic reaction. Following national discussions, she was enrolled for a trial of a TPO-receptor agonist. However, whilst awaiting entry into this trial, she developed spontaneous remission – 2.5 years following initial diagnosis. Chronic ITP is rarely associated with significant thrombocytopenia and symptomatology. Medical and surgical treatments can effect remission but therapeutic cure is unusual. It is therefore essential to weigh up the risk balance when considering treatment. This case clearly highlights this point and prompts consideration of the indications for medical treatment in chronic ITP and of where the risk-benefit balance lies in complex cases such as this.

Inhibitory human antichimeric antibodies to rituximab in a patient with pemphigus

Inhibitory human antichimeric antibodies to rituximab in a patient with pemphigus

A randomized controlled trial of rituximab for the treatment of severe cryoglobulinemic vasculitis

To conduct a long-term, prospective, randomized controlled trial evaluating rituximab (RTX) therapy for severe mixed cryoglobulinemia or cryoglobulinemic vasculitis (CV). Fifty-nine patients with CV and related skin ulcers, active glomerulonephritis, or refractory peripheral neuropathy were enrolled. In CV patients who also had hepatitis C virus (HCV) infection, treatment of the HCV infection with antiviral agents had previously failed or was not indicated. Patients were randomized to the non-RTX group (to receive conventional treatment, consisting of 1 of the following 3: glucocorticoids; azathioprine or cyclophosphamide; or plasmapheresis) or the RTX group (to receive 2 infusions of 1 gm each, with a lowering of the glucocorticoid dosage when possible, and with a second course of RTX at relapse). Patients in the non-RTX group who did not respond to treatment could be switched to the RTX group. Study duration was 24 months. Survival of treatment at 12 months (i.e., the proportion of patients who continued taking their initial therapy), the primary end point, was statistically higher in the RTX group (64.3% versus 3.5% [P < 0.0001]), as well as at 3 months (92.9% versus 13.8% [P < 0.0001]), 6 months (71.4% versus 3.5% [P < 0.0001]), and 24 months (60.7% versus 3.5% [P < 0.0001]). The Birmingham Vasculitis Activity Score decreased only after treatment with RTX (from a mean ± SD of 11.9 ± 5.4 at baseline to 7.1 ± 5.7 at month 2; P < 0.001) up to month 24 (4.4 ± 4.6; P < 0.0001). RTX appeared to be superior therapy for all 3 target organ manifestations, and it was as effective as conventional therapy. The median duration of response to RTX was 18 months. Overall, RTX treatment was well tolerated. RTX monotherapy represents a very good option for severe CV and can be maintained over the long term in most patients.

Long Term Follow up of Patients with Immune Thrombocytopenia Receiving Rituximab

Abstract 4675 Introduction:Rituximab has been used in the management of chronic immune thrombocytopenia (ITP) with promising results. The risk of losing response, however, is yet to be determined with long term follow up. Method:We retrospectively analyzed 32 consecutive patients (20 females, 12 males) with ITP (including 6 patients with secondary ITP) treated with rituximab in two tertiary care hospitals in Oman between May 2006 and May 2011. Response criteria were based on the International Consensus report (Rodeghiero F et al. Blood 2009). Result:The median age at diagnosis was 25 years (range, 4 – 58). Clinical presentation ranged from mild echymosis to more severe central nervous system bleeding. Patients received a median of one line of therapy before rituximab (range, 1–4), including 3 patients who failed splenectomy. Patients received intravenous rituximab using 375 mg/m2 once weekly for 4 weeks. The median time from diagnosis to receiving rituximab was 21 months (range, 1– 177). Only one patient was positive for Hepatitis C virus, but no hepatitis B or HIV positive in this cohort. Anti nuclear antibody was positive in 34% (10/29) of patients. The median hemoglobin and platelet counts at diagnosis were 12 g/dl (range, 5–16) and 11×109/L (range, 1–60) respectively. The median follow up time after rituximab was 26 months (95% confidence interval: 11–40). The overall cumulative response rate was 59% (partial response of 15% and complete response of 44%). The median time to respond was 30 days (Standard error [SE] 49) with a response rate of 44% at 4 weeks (95% Confidence interval: 29–62%). The multivariable Cox model analysis (variables include: age at diagnosis, gender, number of previous therapies and primary vs. secondary) revealed none of the variables included to be statistically significant. The cumulative rate of loss of response was 32% (6/19) with a median time to lose response of 54 months (SE, 0.03). In patients who lost response, the median time to lose response was 17 months (SE, 14). Of the 6 patients who lost response, 4 received a second course of rituximab and all 4 achieved a full response. No major side effects to rituximab were reported during the follow up. Conclusion:Rituximab is an effective and a well tolerated second line therapy for ITP. The response to rituximab can be maintained for a long duration with a high rate of response after retreatment. None of the pretreatment variables studied carried a significant predictive value for response. The study was limited by the small sample size and further larger prospective studies are recommended. Disclosures:Off Label Use: Rituximab was used in our study as a second line for the management of chronic immune thrombocytopenia.

Multicentre Retrospective Analysis of Rituximab Use in the Treatment of Steroid Resistant Autoimmune Haemolytic Anaemia in Ireland,

Abstract 3171▪▪This icon denotes a clinically relevant abstractAutoimmune haemolytic anaemia (AIHA) is characterised by severe haemolysis due to development of auto antibodies directed against patient's own red cells. Rituximab is a chimeric monoclonal antibody that specifically depletes B cells by targeting CD20 on both immature and mature B lymphocytes We evaluated the use of Rituximab in patients with AIHA who are refractory to conventional Immunosupression in 5 centres in ireland. Methods:24 cases of AIHA from five centres in the Republic of Ireland were identified who were treated with Rituximab at the standard dose of 375mg/m2 weekly for four weeks. All patients had received prior therapy with steroids and 50% of patients received two or more courses of Immunosupression. One patient had splenectomy prior to Rituximab. Five patients had an underlying lymphoproliferative disorder and two had a myeloproliferative neoplasm. Response was assessed at 1,3,6,12,36, 48 and 60 months. Medium duration of follow up was 34 months. Response was defined as normalisation of Haemoglobin concentration and haemolytic parameters reticulocyte count, bilirubin and lactate dehydrogenase (LDH).Overall response to Rituximab was 83.3% at 28 days post treatment. Four patients responded to Rituximab in combination with other Immunosupression such as Azathioprine or low dose steroids. Medium response duration was 11.5 months. Sustained response at 1 year, 2 years and 4 years post treatment were 60%, 55% and 30% respectively. Rituximab was well tolerated without significant complications in the majority of patients. One patient developed neutropenic sepsis. One patient received second course of Rituximab after relapse within a year and had sustained response of over two years after the second course. Conclusion:Rituximab is a safe and effective treatment for patients with AIHA who are resistant to steroids.The majority of patients will initially respond but a significant number will gradually relapse over time. Re-treatment with rituximab maybe considered on relapse. Disclosures:No relevant conflicts of interest to declare.