Single Infusion Of Rituximab Research Articles

Rituximab as Initial Therapy in Adult Patients With Minimal Change Disease

Rituximab as Initial Therapy in Adult Patients With Minimal Change Disease

The Efficacy and Safety of Rituximab in ANCA-Associated Vasculitis: A Systematic Review.

Background and aim: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a rare multisystem autoimmune disease developed by autoantibody production against human neutrophilic granulocytes, including proteinase-3 (PR3) and myeloperoxidase (MPO). The management of AAV patients is difficult due to the multiorgan involvement, high rate of relapse, and complications of immunosuppressive agents that make it challenging. This study aims to investigate the efficacy and safety of rituximab (RTX) therapy in patients with granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA) subtypes. Method: The PubMed/Medline database was searched for any studies related to RTX therapy in ANCA-associated vasculitis (GPA and MPA subtypes), from inception to 1 August 2022, and proceeded in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Results: Our search resulted in 1082 initial records. After the elimination of review papers, irrelevant studies, and non-English records, 223 articles were included, and the data related to the efficacy and safety of RTX therapy were extracted. Several randomized and non-randomized studies showed that RTX is an effective treatment option for patients with AAV. Most of the studies showed the very effective effect of RTX in controlling disease in AAV patients, including pediatrics, adults, and elderlies, although RTX cannot completely prevent relapse. However, maintenance therapy helps delay the disease's relapse and causes sustained remission. Not only the licensed dose (375 mg/m2 intravenous per week for 4 weeks) could induce disease remission, but studies also showed that a single infusion of RTX could be effective. Although RTX could resolve many rare manifestations in AAV patients, there are few reports showing treatment failure. Additionally, few sudies have reported the unexpeted worsening of the disease after RTX administration. Generally, RTX is relatively safe compared to conventional therapies, but some serious adverse effects, mainly infections, cytopenia, hypogammaglobinemia, malignancy, and hypersensitivity have been reported. Conclusions: RTX is an effective and relatively safe therapeutic option for AAV. Studies on the evaluation of the safety profiles of RTX and the prevention of severe RTX-related side effects in AAV patients are required.

Efficacy and Safety of Desensitization Therapy in Pediatric Heart Transplant Candidates

<h3>Purpose</h3> Allosensitization to human leukocyte antigen (HLA) in pediatric heart transplant candidates is associated with higher waitlist, post-transplantation mortality and antibody mediated rejection. As limited safety/efficacy data exist on pre-transplant desensitization regimen, we reviewed our institution's experience. <h3>Methods</h3> We reviewed the medical records of 12 highly sensitized (average cPRA = 68%) pediatric heart transplant candidates who underwent desensitization therapy at the University of Virginia Hospital between 2014 and 2020. The following data were collected: individual immunosuppression regimen, pre and post desensitization levels of antibody burden, documented side effects, and incidence of antibody mediated rejection. <h3>Results</h3> The majority of patients received an oral immunosuppressive regimen of Prednisone (0.3 mg/kg/day to max dose of 12.5 mg) and an antimetabolite (Cellcept 60 mg/kg/dose q12 up to 1,000 mg q12 or Imuran 1-2 mg/kg/day) followed by a single infusion of Rituximab (375 mg/m2) and monthly intravenous immunoglobulin (IVIG 2 g/kg) infusions; plasmapheresis was used in one patient and Bortezomib was used in two. cPRA decreased by an average of nearly 20% after an average of 17.5 weeks (Table 1). HLA I antibodies were more susceptible to desensitization than HLA II antibodies (60% vs 36% average antibody reduction, respectively). Immunosuppression medications were well tolerated with only one patient requiring Rituximab discontinuation due to hypotension, tachycardia and respiratory distress. There were no cases of antibody mediated rejection in those patients who underwent transplantation. <h3>Conclusion</h3> In our cohort, B-cell/ antibody targeted therapies were safe and effective in improving allosensitization and allowing for successful transplantation, though HLA II antibodies were more resistant to therapy. Larger scale studies are needed.

Successful Eradication of De Novo C1q-Binding Donor-Specific Antibodies with Rituximab Monotherapy

<h3>Introduction</h3> Antibody-mediated rejection (AMR) is an increasingly recognized cause of lung transplant allograft failure. Treatment of AMR involves combination therapy that is often poorly tolerated or unsuccessful with regimens involving the combination of intravenous immunoglobulins, plasmapheresis, and proteasome inhibitors, complement, or CD20 therapy. The development of DSAs alone, specifically complement activating C1q-binding DSAs, has been identified as an independent risk factor for solid organ transplant allograft dysfunction. Previous studies have examined the efficacy of combination therapy involving the anti-CD20 antibody rituximab to preemptively eliminate DSAs. Here we report on a case of successful eradication of de novo C1q-binding DSAs in a lung transplant recipient using rituximab. <h3>Case Report</h3> Our patient underwent double-lung transplantation for idiopathic pulmonary fibrosis in August 2019. His post-transplant course was notable for multiple episodes of acute cellular rejection (ACR) requiring burst-dose corticosteroids. DSA titers were monitored every three months post-transplant. At six months, de novo DSAs were detected (DQ7 with DQA1*05) at a mean fluorescence intensity (MFI) of 3623 (low-moderate) (Figure 1). These subsequently rose to an MFI of 11281 (strong) with development of C1q positivity that peaked at an MFI of 15038. Given his frequent episodes of ACR, the strong C1q positivity, and concerns regarding his ability to tolerate therapy for potential future AMR, he was preemptively treated with a single infusion of rituximab (375 mg per meter-squared body surface area). Follow-up DSA titers demonstrated near-total elimination of the C1q component (MFI 403). The patient tolerated the treatment without issue and continues to demonstrate improvement in his allograft function. <h3>Summary</h3> Rituximab monotherapy can be considered preemptively in patients with C1q-binding DSAs that may not tolerate traditional treatment of antibody-mediated rejection.

Efficacy and safety of rituximab in peripheral ulcerative keratitis associated with rheumatoid arthritis

ObjectivePeripheral ulcerative keratitis (PUK) is a rare but severe ocular complication of rheumatoid arthritis (RA). It can be considered as an ocular manifestation of rheumatoid vasculitis (RV). Our case series...

Rituximab for very low dose steroid-dependent nephrotic syndrome in children: a randomized controlled study.

Steroid-dependent nephrotic syndrome (SDNS) carries a high risk of toxicity from steroids or steroid-sparing agents. This open-label, randomized controlled trial was designed to test whether the monoclonal antibody rituximab is non-inferior to steroids in maintaining remission in juvenile forms of SDNS and how long remission may last (EudraCT:2008-004486-26). We enrolled 30 children 4-15years who had developed SDNS 6-12months before and were maintained in remission with low prednisone doses (0.1-0.4mg/Kg/day). Participants were randomized following a non-inferiority design to continue prednisone alone (n 15, controls) or to add a single intravenous infusion of rituximab (375mg/m2, n 15 intervention). Prednisone was tapered in both arms after 1month. Children assigned to the control arm were allowed to receive rituximab to treat disease relapse. Proteinuria increased at 3months in the prednisone group (from 0.14 to 1.5g/day) (p < 0.001) and remained unchanged in the rituximab group (0.14g/day). Fourteen children in the control arm relapsed within 6months. Thirteen children assigned to rituximab (87%) were still in remission at 1year and 8 (53%) at 4years. Responses were similar in children of the control group who received rituximab to treat disease relapse. We did not record significant adverse events. Rituximab was non-inferior to steroids for the treatment of juvenile SDNS. One in two children remains in remission at 4years following a single infusion of rituximab, without significant adverse events. Further studies are needed to clarify the superiority of rituximab over low-dose corticosteroid as a treatment of SDNS.

Treatment of IgG4-related pachymeningitis in a patient with steroid intolerance: The role of early use of rituximab

IgG4-related pachymeningitis is a serious inflammatory condition that can present with symptoms of mass effect and focal deficits. The first-line therapy is steroids and second-line is chemotherapy (methotrexate, azathioprine, etc.). We describe a patient with IgG4-related pachymeningitis in whom steroid use was contraindicated and methotrexate was ineffective. During the course of treatment, the patient presented to the emergency department with receptive and expressive aphasia, slurred speech, right-sided neglect, and loss of sensation. After a single infusion of rituximab and anticonvulsants, her symptoms resolved. Our unique case suggests that patients with IgG4-related pachymeningitis might benefit from early initiation of rituximab.

Treatment Outcomes With Rituximab in 100 Patients With Neuromyelitis Optica: Influence of FCGR3A Polymorphisms on the Therapeutic Response to Rituximab.

Despite the increased use of rituximab therapy in neuromyelitis optica spectrum disorder (NMOSD), the overall efficacy and safety of long-term rituximab treatment in a large group of patients is uncertain. Furthermore, the identification of a predictor of rituximab response is an important issue for assessing the individual risk-benefit of therapy and making treatment decisions. To assess the long-term clinical efficacy and safety of rituximab treatment in patients with NMOSD and the influence of fragment c gamma receptor 3A (FCGR3A) polymorphisms on rituximab response. A retrospective review of 100 patients with relapsing NMOSD treated with rituximab for at least 6 months, from February 1, 2006, to January 31, 2015, at the institutional referral center. After induction therapy, a single infusion of rituximab (375 mg/m2) as maintenance therapy was administered whenever a reemergence of CD27+ memory B cells among peripheral blood mononuclear cells occurred. Using an allele-specific polymerase chain reaction-based method, the gene polymorphisms FCGR3A-V158F were assessed. The primary end point was annualized relapse rate; disability (Expanded Disability Status Scale score), safety of rituximab treatment, event of insufficient memory B-cell depletion following rituximab, and time to retreatment of rituximab were secondary end points. By January 31, 2015, a total of 100 patients received repeated rituximab treatment during a median of 67 months. Of these patients, 41 had more than 5 years' follow-up and 24 had more than 7 years' follow-up. The annualized relapse rate was reduced significantly by 96% (mean [SD] annualized relapse rate of prerituximab vs postrituximab, 2.4 [2.0] vs 0.1 [0.6]) and disability improved or stabilized in 96% of patients. Rates of adverse events were generally stable. The FCGR3A-F allele was associated with a risk of relapse while receiving rituximab treatment (additive model, P < .05; recessive model, P = .04; maximum, P = .03) and insufficient memory B-cell depletion (additive model, P = .03; recessive model, P = .03; maximum, P = .03). Repeated rituximab treatment for NMOSD was observed in an increasing number of patients and increasing duration of exposure and maintained good efficacy and a safety profile consistent with previous reports. The finding of a relationship between FCGR3A genetic polymorphisms and rituximab response suggests the importance of individualized rituximab treatment strategies in NMOSD.

Re-treatment with high-dose prednisolone after rituximab infusion for childhood-onset steroid-resistant nephrotic syndrome

Sirs, We read with great interest the article titled “Rituximab treatment combined with methylprednisolone pulse therapy and immunosuppressants for childhood steroid-resistant nephrotic syndrome” by Kamei et al., which has recently appeared in Pediatric Nephrology [1]. In this retrospective observational study of ten childrenwith refractory steroid-resistant nephrotic syndrome (SRNS), seven patients (70 %) achieved complete remission after receiving multiple courses of methylprednisolone pulse therapy (MPT) and immunosuppressive agents administered after one to four doses of rituximab (RTX). Although we agree with their speculation that a RTX infusion may improve the response to various immunosuppressants, such as steroids and cyclosporine A, little information is currently available on the optimal therapeutic protocol for children with refractory SRNS after administration of the biological agent. We previously described a 2-year-old girl with refractory SRNS resistant to nine courses of MPT (total 27 treatments) and cyclosporine A (6–7 mg/kg/day) following RTX infusion. Interestingly, the patient went into complete remission after re-treatment with conventional high-dose prednisolone (PSL, 2 mg/kg/day) administered after an additional RTX infusion within 2 weeks [2]. Recently, we encountered a SRNS patient resistant to multiple courses of MPTand mycophenolate mofetil who also achieved complete remission after re-treatment with high-dose PSL administered after an RTX infusion within a short period of time. This patient, an 8-year-old boy, presented with a 2-week history of significant weight gain and generalized edema. His medical history was significant for chronic kidney disease (estimated glomerular filtration rate 60–70 ml/min/1.73 m) as he had experienced septic shock associated with pneumococcal meningitis at the age of 1 year. On admission, a physical examination showed generalized edema, abdominal distention, and a blood pressure of 111/72 mmHg. His weight was 22.2 kg, which was increased by 2 kg compared to his dry weight. Laboratory investigations were as follows: white blood cell count, 72,000/mm; hemoglobin, 13.7 g/dl; hematocrit, 39.2 %; platelets, 221,000/mm; blood urea nitrogen, 23 mg/dl; serum creatinine, 0.61 mg/dl; sodium, 137 mmol/l; potassium, 4.4 mmol/l; chloride, 107 mmol/l; calcium, 7.7 mg/dl; phosphorous, 4.8 mg/dl; total protein, 3.9 g/dl; albumin, 1.6 g/dl; total cholesterol, 404 mg/dl; serum immunoglobulin G, 202 mg/dl, C3, 105 mg/dl, and C4, 18 mg/dl. Tests with antihepatitis B surface antigen, antihepatitis C antibody, and antinuclear antibody were negative. Urinalysis showed 1+ occult blood and 3+ protein by dipstick. The 24-h urine protein excretion was 4.9 g. Based on these findings, a presumptive diagnosis of idiopathic NS in the course of chronic renal insufficiency was made, and treatment with high-dose PSL (2 mg/kg/day) was initiated without a significant reduction in the amount of proteinuria. Persistent nephrotic-range proteinuria for more than 4 weeks with conventional steroid therapy prompted us to perform a renal biopsy with histology, which showed ischemic glomerular obsolescence. Since nephrotoxic drugs such as cyclosporine A were contraindicated based on the histological findings, the patient was treated with MPT (20 mg/kg/day for 3 consecutive days per week) for 3 weeks, followed by mycophenolate mofetil (30 mg/kg/day) and alternate-day low-dose PSL. However, proteinuria did not return to baseline values. After a single infusion of RTX (375 mg/m), a second course of high-dose PSL (2 mg/kg/ S. Fujinaga (*) Division of Nephrology, Saitama Children’s Medical Center, 2100 Magome, Iwatsuki-ku, Saitama City, Saitama 339 8551, Japan e-mail: f_shuich@d2.dion.ne.jp

Risk factors for early relapse during maintenance therapy after a single infusion of rituximab in children with steroid-dependent nephrotic syndrome

Sir,We readwith great interest the article “Long-term outcome ofchildren treated with rituximab for idiopathic nephrotic syn-drome” by Tellier et al., which was recently published inPediatricNephrology [1].Inaretrospectivemulticenterstudyincluding18Frenchchildrentreatedwithrituximab(RTX)forsteroid-dependent nephrotic syndrome (SDNS), they recom-mendedregularandrepeatedtreatmentwithRTX,arelativelysafe biological agent, with the aim of inducing a long-lastingB-cell depletion period (at least 18–24 months in the Frenchprotocol). However, it remains unclear whether all patientsshouldbere-treatedbecausesomepatientsmaintainremissioneven after B-cell recovery. Furthermore, it is impossible toperform vaccinations during long-term B-cell depletion,which is a critical issue when treating children. In contrast,resultsfromrecentJapaneseprospectivestudieshaverevealedthat maintenance therapy with cyclosporine (CsA) or myco-phenolate mofetil (MMF) following a single infusion of RTXmay eliminate the need to repeat RTX infusions and, conse-quently, decrease the side effects associated with repeateddoses [2, 3]. However, early relapse of NS after RTX therapyis noted in some patients, despite this therapeutic protocol.Onthebasisofourexperienceinasinglecenter,wewouldlike to comment on the risk factors that predict early relapseafterinitialsingle-doseRTXtherapyfollowedbymaintenancetherapy in Japanese children with severe SDNS. BetweenSeptember 2007 and April 2012, a study was conducted atthe Saitama Children’s Medical Center which comprised 37patients (26 boys, 11 girls; mean age 11.7±4.9 years) withpersistent SDNS despite treatment with multiple immunosup-pressive agents who had been initially treated with single-doseRTX (375 mg/m

Epstein–Barr virus reactivation in allogeneic stem cell transplantation is highly related to cytomegalovirus reactivation

Monitoring of Epstein-Barr virus (EBV) load and pre-emptive rituximab is an appropriate approach to prevent post-transplant lymphoproliferative disease (PTLD) occurring after hematopoietic stem cell transplantation (HSCT). This pre-emptive approach, based on EBV-DNA monitoring through a quantitative polymerase chain reaction, was applied to 101 consecutive patients who underwent allo HSCT at our Institute (median age 50). A single infusion of rituximab was administered to 11 of 16 patients who were at high risk for progression to PTLD, defined as a DNA value >10 000 copies/mL. All patients cleared EBV DNAemia, without any recurrences. Main factors significantly associated with high risk for PTLD were as follows: (i) unrelated vs. sibling (26% vs. 7%; p = 0.011); (ii) T-cell depletion (29% vs. 6%; p = 0.001); (iii) graft versus host disease (GVHD; 30% vs. 7%; p = 0.002); and (iv) cytomegalovirus (CMV) reactivation (29% vs. 4%; p = 0.001). Multivariate analysis showed that CMV reactivation was the only independent variable associated with EBV reactivation. We conclude that: (i) a single infusion of rituximab is able to prevent the risk of progression into EBV-related PTLD; and (ii) CMV reactivation is strongly associated with EBV reactivation; therefore, an intensive EBV monitoring strategy could be advisable only in case of CMV reactivation.

Cyclosporine versus mycophenolate mofetil for maintenance of remission of steroid-dependent nephrotic syndrome after a single infusion of rituximab

The efficacy of rituximab (RTX) as the sole therapy for preventing relapses of nephrotic syndrome (NS) is transient in most patients; therefore, the optimal therapy required for maintaining a successful response to a biological agent remains a challenge. We conducted a prospective study to compare the efficacy of cyclosporine (CsA) with that of mycophenolate mofetil (MMF) as maintenance therapy after a single infusion of RTX. Of 29 patients with persistent steroid-dependent NS despite the use of CsA and/or MMF, 13 without chronic nephrotoxicity continued CsA therapy, maintaining a 2-h post-dose CsA level of 400-500 ng/ml (CsA group). The remaining 16 were treated with MMF, maintaining a pre-dose level of 2-5 μg/ml of mycophenolic acid (MMF group). The median duration of CsA and MMF treatment was 18 and 19 months, respectively. Despite the mean number of relapses before RTX treatment being significantly lower in the MMF group than in the CsA group (2.3/year vs. 4.6/year, p < 0.01), treatment failure occurred more frequently in the MMF group (7/16) than in the CsA group (2/13). The rate of sustained remission was also significantly higher in the CsA group than in the MMF group (p < 0.05). In patients with severe steroid-dependent NS, CsA appears to be more effective than MMF for maintaining remission after a single infusion of RTX.

難治性ステロイド依存性ネフローゼ症候群に対するリツキシマブ単回投与後のシクロスポリン / ミコフェノール酸モフェチルによる寛解維持効果

難治性ステロイド依存性ネフローゼ症候群に対するリツキシマブ単回投与後のシクロスポリン / ミコフェノール酸モフェチルによる寛解維持効果

The Addition of Rituximab and/or Alpha-Interferon to High Dose Chemotherapy and Autologous Stem Cell Transplantation for Patients with Relapsed Follicular Lymphoma Produces Durable Progression Free Survival and Molecular Remissions

AbstractAbstract 1357 Introduction:High dose chemotherapy (HDT) with autologous stem cell transplantation (ASCT) is historically effective treatment for patients with relapsed follicular lymphoma (FL) but relapse is common possibly due to contaminated stem cell grafts or inadequate eradication of primary disease. The addition of immunotherapy to HDT/ASCT may augment “in vivo” graft purging and achieve more effective eradication of minimal residual disease (MRD) post ASCT. This may lead to improved PFS and OS. Methods:We conducted 3 sequential prospective phase 2 trials of HDT/ASCT combined with immunotherapy in patients with relapsed FL from 1997–2010. Protocol 1 (n=13) used a-interferon 3 MU/m2 SC TIW for 2 years post ASCT. Protocol 2 (n=23) used a single infusion of rituximab (R) 375 mg/m2 for ‘in vivo’ purging 3–5 days pre-stem cell collection and 2 sets of 4 weekly R at 2 and 6 months post ASCT respectively. Protocol 3 (n=32) used 3 infusions of R 375 mg/m2 pre stem cell collection, followed by a-interferon 3 MU/m2 SC TIW × 2 years + R 375mg/m2 × 6 weekly infusions post ASCT. Eligibility included adult patients age 18–65 with stage III or IV follicular lymphoma grades 1–3a in first or second relapse. Salvage chemotherapy was either CHOP or DHAP depending on prior anthracycline exposure. High dose therapy was cyclophosphamide, carmustine, and etoposide (CBV). Minimal residual disease (MRD) assessment of t(14; 18) by quantitative PCR was serially performed in blood, PBSC and marrow. Studies were REB approved and all patients gave informed consent. Results:Sixty-eight patients from the 3 trials are included. Median age at study enrolment was 47 (30-71) and patients were a median of 31 mo (9-197) from diagnosis. 54% were male. Median FLIPI score was 2. Median # of prior chemotherapies was 1. Median number of cycles of salvage chemotherapy was 4 (2 - 10). 63 patients proceeded to ASCT. 5 patients were not transplanted either do to disease progression (2), or failed stem cell mobilization (3). Baseline characteristics of the patients enrolled in the three trials were similar, with the exception of rituximab(R) exposure in 22% of the patients in Protocol 3. 4 (6%) patients were lost to follow up.Median time to death or last follow was 84.5 mo (7-166). 32 patients (47%) relapsed and 20 (29%) have died. Median follow up times for each trial were 116, 99 and 57 mo. Actuarial median OS for Protocol 1 was 136 mo from enrolment and has not yet been reached for Protocols 2 and 3. Actuarial median PFS for Protocols 1 and 3 are 49 and 78 mo respectively and has not yet been reached for Protocol 2.MRD assessment by PCR was collected on 48 patients. Compared with study 1, the increased use of R pre SC collection improved in vivo purging by 2 logs. In Protocols 1 and 2, most still had detectable disease in the graft to a sensitivity of 1 cell/100,000. In Protocol 3, 56% had MRD negative apheresis products. 91% of 46 evaluable patients achieved molecular remission post stem cell transplant.Thirteen patients (19%) developed secondary malignancies post ASCT with a median time to malignancy of 88.5 mo (39-144). 1 patient developed 2 distinct malignancies. Secondary malignancies present were: MDS (4), AML (1), ALL (1), basal cell carcinoma (2), squamous cell carcinoma (3), thyroid cancer (1), non small cell lung cancer (1) and adenocarcinoma of unknown origin (1). Five (7%) patients transformed to DLBCL, with a median time to transformation post ASCT of 43.5 mo (17-142).The majority of patients who received rituximab immunotherapy pre and post ASCT developed persistent hypogammaglobulinemia. 17 patients (26%) developed interstitial pneumonitis or >2 respiratory complications post rituximab. 4 patients (6%) require monthly IVIG to treat recurrent respiratory infections. 10 patients (15%) developed herpes zoster <90 days post ASCT.15% and 30% of patients in Protocols 1 and 3 did not complete the 2 years of alpha-IFN post ASCT secondary to one or more of depression, fatigue or cytopenias. Conclusion:HDT + ASCT combined with R +/− a-IFN produces durable PFS and molecular remissions but is associated with prolonged hypogammaglobulinemia and higher rates of interstitial pneumonitis. Three infusions of R pre SC collection achieve higher rates of molecular remission. Compliance with 2 years of a-IFN added to R post ASCT is poor and may not add clinical benefits to R alone. The additional role of HDT/ASCT in the era of R-chemotherapy for FL needs to be explored. [Display omitted] [Display omitted] Disclosures:No relevant conflicts of interest to declare.

Cost-effectiveness treatment with Rituximab in patients with rheumatoid arthritis in real life

The cost-effectiveness of treatments that have the potential to change the "natural history" of a chronic progressive disease has to be evaluated over the long term. Cost-effectiveness estimates have been based on the concept that, with treatment, patients will not progress to the next level(s) of disease severity or will take a longer time to progress, thus avoiding or delaying the high costs and low utility associated with more severe disease. This analysis focused on the use of Rituximab in treating patients with moderate to severe RA for whom at least one anti-TNFα blocking agent had failed. The aim of our study was to evaluate the cost-effectiveness in 32 patients with rheumatoid arthritis in therapy with a single infusion of Rituximab 1,000 mg given on days 1 and 15 of each month for 1 year. After 6 months of treatment, we observed for all 32 patients a total quality-adjusted life year (QALY) gained of 11,840 with an average of 0.37 QALY for a single patient, a treatment cost of euro 5,610 and a QALY/cost ICER (incremental cost-effectiveness ratio) of euro 15,114. After 1 year of treatment, we observed data for 28 patients with a total QALY gained of 11,480 with an average of 0.41 QALY for a single patient, a treatment cost of euro 9,690 and a QALY/cost ICER (incremental cost-effectiveness ratio) of euro 23,696. The benefit of using Rituximab is cost-effectiveness with a QALY/gained under the acceptable threshold of euro 50,000 in our observational study. These are important data for discussion from the economic point of view when we choose a biologic therapy for rheumatoid arthritis in clinical practice.

Acute Respiratory Distress Syndrome after Rituximab Infusion

Rituximab, a humanized monoclonal antibody approved for malignant lymphoma, is being increasingly, effectively, and safely used for immune thrombocytopenic purpura (ITP) and other humoral autoimmune disorders. We report the case of a 43-year-old man with ITP refractory to steroids and intravenous immunoglobulin who developed acute respiratory distress syndrome (ARDS) after a single infusion of rituximab. Dyspnea, hypoxemia, and pleuritic chest pain occurred within 24 hours of rituximab administration, and there was no other apparent explanation. Progressive hypoxemia mandated endotracheal intubation 1 week after rituximab administration and led to death 4 weeks after admission. ARDS has been associated with the administration of other monoclonal antibodies, such as infliximab, gemtuzumab ozogamicin, and OKT3 and is believed to be directly mediated by release of proinflammatory cytokines. ARDS is rarely associated with rituximab infusion for lymphoproliferative disorders, but it should be considered by those administering rituximab, especially when a patient develops severe pulmonary symptoms soon after infusion.

Prevention of Epstein-Barr virus–lymphoproliferative disease by molecular monitoring and preemptive rituximab in high-risk patients after allogeneic stem cell transplantation

Recipients of a partially T-cell-depleted (TCD) allogeneic stem cell transplantation (allo-SCT) developing reactivation of Epstein-Barr virus (EBV) with quantified viral DNA levels exceeding 1000 genome equivalents/milliliter (geq/mL) are at high risk for EBV-lymphoproliferative disease (EBV-LPD). We studied whether preemptive therapy with rituximab prevents EBV-LPD, LPD-mortality, and abrogates viral reactivation in high-risk patients. We monitored 49 recipients of a TCD allo-SCT weekly for EBV reactivation by quantitative real-time polymerase chain reaction (PCR). Preemptive therapy by a single infusion of rituximab was given to patients with viral reactivation more than or equal to 1000 geq/mL. Results were compared with an historical control group of patients retrospectively monitored for EBV reactivation at similar intervals. There were 17 prospectively monitored patients who showed EBV reactivation more than or equal to 1000 geq/mL and 15 received preemptive therapy. Median time to preemptive therapy was 113 days (range, 41-202 days) after SCT. There were 14 patients who showed complete response (CR) as characterized by prevention of EBV-LPD and complete clearance of EBV-DNA from plasma, which was achieved after a median number of 8 days (range, 1-46 days). One patient progressed to EBV-LPD despite preemptive therapy, but obtained CR after 2 infusions of rituximab and donor lymphocyte infusion. There were 2 patients who had already developed EBV-LPD prior to preemptive rituximab, but obtained CR following 2 rituximab infusions. Comparison of this prospectively followed series to our historical cohort with the same high-risk profile showed a reduction of EBV-LPD incidence (18% +/- 9% versus 49% +/- 11%, respectively) and a complete abrogation of LPD-mortality (0% versus 26% +/- 10%, respectively) (P =.04) at 6 months from EBV-DNA more than or equal to 1000 geq/mL. Frequent quantitative monitoring of EBV reactivation and preemptive therapy by rituximab improves outcome in patients at high risk of EBV-LPD. (Blood. 2002;99:4364-4369)