Rituximab treatment of ANCA-associated vasculitis

ABSTRACT

Introduction

Rituximab, an anti–B-cell biological therapy, has been investigated in several clinical trials on antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAVs).     

小剂量美罗华联合重组人血小板生成素治疗难治性特发性血小板减少性紫癜的护理

目的探讨小剂量美罗华联合重组人血小板生成素(rh TPO)治疗难治性特发性血小板减少性紫癜(ITP)的疗效及其护理。方法对诊断为难治性ITP的4例患者采用小剂量美罗华联合rh TPO治疗,治疗过程中实施有效的心理护理,严格规范药液的保管、配置及输注,积极预防和处理药物不良反应,并对副作用进行严密观察和护理。结果 4例患者中,1例获完全反应(CR),3例获部分反应(PR),发热1例、肝功能异常1例,所有患者均顺利完成治疗。结论小剂量美罗华联合rh TPO为难治性ITP的治疗提供了新途径,是一种安全有效的治疗方法,精心的护理能有效预防药物的毒副作用,保证治疗效果。     

Autoimmune cytopaenia after paediatric intestinal transplantation: a case series

Autoimmune cytopaenia is a rare, but severe complication after solid organ transplantation. We retrospectively analysed 57 paediatric intestinal transplants performed in 49 patients between 1999 and 2009. Autoimmune cytopaenia was observed in six patients; it appeared after an average of 10 months post‐transplant. Warm autoimmune haemolytic anaemia was developed in three patients, cold autoimmune haemolytic anaemia in one and two presented a mixed type. Incidence and causes for haematological cytopaenia such as the following were investigated: immunosuppression, major blood mismatch, viral infection, malignancy, passenger lymphocyte syndrome and lymphoproliferative disorders. Initial treatment included high‐dose steroids, intravenous immunoglobulin, plasmapheresis and maintenance of body temperature above 37 °C in those with cold autoantibodies. Inclusion of the spleen in multivisceral transplants seems to be an important risk factor. All patients, except one, relapsed after classic therapy, requiring additional treatments. Sirolimus conversion was performed in four patients. One died after infection. The immunosuppressive therapies associated with other concomitant factors, such as viral infections, lymphoproliferative disorders, graft‐versus‐host disease, passenger lymphocyte syndrome and the inclusion of the spleen as part of multivisceral graft seem to play an important part in the development of autoimmune processes after intestinal transplantation. Therapy is not well established, especially in those resistant to first‐line treatment.     

Treatment of systemic lupus erythematosus with epratuzumab

Systemic lupus erythematosus is a prototypic autoimmune disease characterized by abnormalities in the activity of B-cells and T-cells. A novel specific treatment for autoimmune diseases is B-cell depletion with monoclonal antibodies. Epratuzumab is a monoclonal antibody that targets CD22 antigen on B-cells. Initial phase II and two terminated early phase III studies suggest that treatment of systemic lupus erythematosus with this immunomodulatory agent is effective, well tolerated and significantly improves the patient's quality of life. In vitro studies and clinical trials with non-Hodgkin lymphoma patients indicate epratuzumab can potentially serve as a complementary drug in combination therapy with another inhibitor of B-cell activity, rituximab, which is a monoclonal anti-CD20 antibody.     

小剂量利妥昔单抗注射液联合环孢素A治疗难治性ITP的临床观察

目的:探讨小剂量利妥昔单抗注射液(通用名为利妥昔单抗注射液)联合环孢素A治疗难治性特发性血小板减少性紫癜(简称难治性ITP)的疗效。方法:38例诊断为难治性ITP患者随机分为观察组和对照组,观察组采用小剂量利妥昔单抗注射液联合环孢素A治疗,对照组采用大剂量地塞米松冲击联合硫唑嘌呤治疗,并评估两组患者的近期及远期疗效和副作用。结果:观察组的近期及远期疗效优于对照组,2组间差异有显著性(P<0.05),除肝功能方面,不良反应的其他指标的比较,2组间差异无显著性(P>0.05)。结论:小剂量利妥昔单抗注射液联合环孢素A可作为难治性ITP的有效治疗手段之一。     

Reactivation of overt and occult hepatitis B infection in various immunosuppressive settings

The aim of the study was to evaluate clinical and virological differences in HBV reactivation between patients with overt and occult HBV infection. Twenty-three consecutive patients with symptomatic HBV reactivation occurring during or after immunosuppressive therapy were enrolled in a retrospective study: 10 with reactivation of overt HBV infection (overt group) and 13 of occult HBV infection (occult group). Twenty-one patients were treated with nucleot(s)ide analogues after HBV reactivation. Regimens including rituximab or fludarabine were administered more frequently in the occult group (61% vs. 31%, respectively). HBV reactivation was severe frequently in the overt (40%) and occult groups (38.4%). Patients in the overt group showed higher HBV-DNA titers (1.1 × 10(8) ± 1.4 × 10(8) vs. 5.1 × 10(5) ± 6.8 × 10(5) IU; P < 0.005). Seven patients died during HBV reactivation, two in the overt and five in the occult group. Of these seven patients, two remained untreated and five had been treated with Lamivudine; of the 16 patients showing remission of HBV reactivation, four had been treated with Lamivudine, four with Entecavir, two with Telbivudine, and six with Lamivudine plus Adefovir. It is concluded that HBV reactivation is life-threatening in patients with diseases inhibiting the immune response and/or receiving immunosuppressive drugs. Supportive therapy without antiviral drugs or Lamivudine monotherapy may not be effective for treating patients with HBV reactivation.     

Rituximab as rescue therapy in anti-neutrophil cytoplasmic antibody-associated vasculitis: a single-centre experience with 15 patients

Background. B-cell depletion with rituximab, a chimeric anti-CD20antibody, is a novel treatment for refractory and relapsingANCA-associated small-vessel vasculitis. Data are limited andmost reports describe single patients or small numbers of patientsfollowed prospectively. Methods. We report a single-centre experience with 15 patientswho received rituximab for refractory or relapsing ANCA-associatedvasculitis. All patients had been treated with corticosteroidsand cyclophosphamide and a variety of other second-line immunosuppressiveagents. None of the patients had evidence of infection and receivedfour infusions of 375 mg/m² of rituximab. Disease activity wasassessed in accordance with the Birmingham Vasculitis ActivityScore (BVAS). BVAS, C-reactive protein and ANCA titres wererecorded at baseline and during follow-up. Results. B-cell depletion was achieved in all patients. Partialor complete remission was seen in 14 of 15 patients with a significantdecline in BVAS compared to baseline (P < 0.007). One patientwith granulomatous ANCA-associated vasculitis did not respondto rituximab. There were no side effects during rituximab infusion.Transient leucopenia was observed in two patients. One patientwith bronchial stenosis died of pneumonia 5.5 months after theinitiation of rituximab treatment. One initially anti-HBc-positive/HBsAg-negativepatient experienced a reactivation of hepatitis B, developedend-stage renal failure and died after refusal of dialysis. Conclusions. We report the largest case series of rituximabuse for ANCA-associated vasculitis so far. Our data supportthat the drug is capable of inducing partial or complete remissionin refractory or relapsing patients. Leucopenia and infectiouscomplications remain a matter of concern.     

Cytomegalovirus infection following renal transplantation in patients administered low-dose rituximab induction therapy

Anti-CD20 antibody (rituximab) is recently being used as a B cell-depleting agent in renal transplantation (RTx). However, the incidence of infectious complications associated with rituximab therapy remains uncertain. We evaluated the incidence of cytomegalovirus (CMV) infection associated with rituximab therapy in RTx. A total of 83 patients were enrolled. The immunosuppressive regimen consisted of tacrolimus or cyclosporin, mycophenolate mofetil, methylprednisolone and basiliximab. In 54 patients, only one dose of rituximab (200 or 500 mg/kg body weight) was given before RTx. A total of 25 of 43 (58.1%) recipients who were CMV seropositive prior to RTx and who received rituximab induction therapy developed CMV infection, compared to 18 of 24 (75%) CMV seropositive recipients who did not receive rituximab therapy ( P  = 0.1676). A total of 8 of 11 patients who were CMV seronegative prior to RTx and who received rituximab developed CMV infection. However, CMV seroconversion was seen in all 8 of these infected patients. Low-dose rituximab induction therapy in renal transplant recipients appears to have no influence on the incidence of CMV infection and CMV seroconversion. However, we have to consider anti-CMV prophylaxis therapy, because of high incidents of CMV infection, especially for CMV seronegative recipients who received rituximab.     

Successful treatment of refractory generalized myasthenia gravis with rituximab

Objective:  Myasthenia gravis (MG) is an autoimmune neuromuscular disorder for which current therapies carry a high risk of side-effects and may be insufficient in stabilizing the clinical status. Many therapeutic options can be ruled, such as thymectomy, corticosteroids, azathioprine, cyclophosphamide, mycophenolate mofetil, methotrexate, intravenous immunoglobulin (IVIg) or less frequently plasmapheresis must be ruled.
Methods:  We followed prospectively six patients with MG who presented with a poor response to two or three lines of immunosuppressive conventional drugs associated with oral corticosteroids. All but one were acetylcholine receptor negative and three were anti-MuSK positive. IVIg did not improved the neurological status and all patient required high doses of cholinesterase inhibitors.
Results:  Rituximab was introduced with a mean follow-up of 1.5 years (375 mg/m², days 1, 8, 15, 28 during the first month and then one dose every 2 months). After 2 years of follow-up, all patients stopped corticosteroids and tapered off cholinesterase inhibitors from 60 to 180 mg/day without severe infectious events.
Conclusion:  Rituximab, a chimeric IgG k monoclonal antibody that target CD20 is used for the treatment of relapsing/refractory CD20 positive low-grade non-Hodgkin's lymphoma and other autoimmune neuromuscular diseases. Four previous short reports have described a good response of MG associated with lymphoma with rituximab. It appears to be a promising and effective drug for the treatment of MG without lymphoma, with a substantial benefit to the clinical status and good tolerability.     

Evaluation of the off-label usage of rituximab in a large teaching hospital in New South Wales

A retrospective review of patients receiving rituximab off label in a large teaching hospital was conducted between July 2002 and January 2006. The indication, dosing regimen, efficacy and cost of rituximab were evaluated. Rituximab was prescribed for three clinical indications; acute organ transplant rejection, post-transplant lymphoproliferative disease and autoimmune disease. On average, 600 mg of rituximab was prescribed weekly for 4 weeks, costing the hospital $108,739.37. We suggest an initial approval for a limited number of doses with subsequent approval dependent on improvement in predefined clinical or biochemical end-points. Furthermore, we suggest an Australia-wide central database be established to enable delineation of the optimal dosing schedule, as well as monitoring of clinical outcome.