Chimeric anti-CD20 Monoclonal Antibody Research Articles

Assessment of rituximab-abbs, a biosimilar, and rituximab outcomes in patients with CLL or NHL: A real-world UK study

BackgroundRituximab (chimeric anti-CD20 monoclonal antibody) treatment is approved for chronic lymphocytic leukemia (CLL) and non-Hodgkin lymphoma (NHL). Rituximab-abbs (first biosimilar approved in 2017) is expected to significantly reduce healthcare economic burden due to lower acquisition costs. This non-interventional, non-comparative study assessed real-world effectiveness and tolerability of rituximab-abbs and rituximab in treatment-naive patients with CLL or NHL. Materials and methodsVia an online physician survey, 46 UK-registered hematologists and oncologists retrospectively reported on randomly selected patients aged ≥18 years with CLL or NHL with rituximab-abbs or rituximab as first-line immunotherapy. Overall, 201 patient charts were examined across 4 cohorts: rituximab-abbs in CLL, rituximab-abbs in NHL, rituximab in CLL, rituximab in NHL. ResultsDemographic profiles across cohorts were similar. Most patients (94 %–100 %) received combination therapy (rituximab-abbs or rituximab mainly with chemotherapy). For both treatments, overall response rate (94 %–98 %) and 1-year overall survival (98 %–100 %) were very high for patients with CLL or NHL. Most common serious adverse events were neutropenia, fatigue, anemia and infusion reactions. The majority of patients (54 %–66 %) did not experience a grade ≥3 adverse event. Healthcare resource utilization was similarly high across cohorts, driven by diagnostic testing, oncologist office visits, and day-case hospital admissions; many patients required supportive medical therapies. Mean annual savings of ∼£1000/patient driven by acquisition costs occurred with rituximab-abbs versus rituximab, administration costs were similar. ConclusionRituximab-abbs and rituximab demonstrated similar effectiveness and tolerability in treating CLL and NHL in routine UK clinical practice and demonstrate the utility of the biosimilar as a cost-saving alternative treatment.

A Rare Case of Rituximab Induced Allergic Interstitial Nephritis with a Good Response to Glucocorticoids

Rituximab is a chimeric anti-CD20 monoclonal antibody that has been widely used to treat CD 20 positive hematologic malignancies and some autoimmune conditions. Although usually well tolerated, an increasing number of serious complications related to rituximab have been noted with its wide usage. We report a 67-year-old man who developed biopsy-proven Allergic Interstitial Nephritis (AIN) after treatment with rituximab for his Primary Central Nervous System Lymphoma (PCNSL). Rituximab-induced AIN was confirmed by kidney biopsy, and his kidney function improved to his baseline with supportive care and four weeks of steroid treatment. While rare, AIN could be a possible adverse effect of rituximab. To our knowledge, this is the first case report of a biopsy-proven AIN from rituximab. The association of AIN and rituximab in our case necessitates a high index of suspicion to facilitate early detection of AIN and timely discontinuation of the offending medication. Keywords: Rituximab; Drug induced allergic interstitial nephritis.

Biologics in autoimmune bullous diseases: Current scenario.

Autoimmune bullous diseases can be intraepidermal (pemphigus group of disorders) or subepidermal (pemphigoid group of disorders). The treatment of these disorders chiefly comprises corticosteroids and immunosuppressant adjuvants like azathioprine and mycophenolate mofetil. Autoantibodies are the main mediators of these diseases. Rituximab, a chimeric anti-CD20 monoclonal antibody targeting B-cells, has emerged as an excellent treatment option for refractory pemphigus vulgaris in the last decade. Since then, many new biologics have been proposed/explored for managing autoimmune bullous diseases. These hold potential for greater efficacy and lesser adverse effects than conventional immunosuppressants. In this review, we discuss the role of various biologics in the treatment of autoimmune bullous diseases, followed by a brief discussion on the drawbacks to their use and new developments in this area.

Evaluation of the Safety and Tolerability of Rapid Infusion of Biosimilar Rituximab Truxima® — the University College London Hospitals (UCLH) Experience

▪Rituximab is a chimeric anti-CD20 monoclonal antibody approved in the EU (MabThera®; Roche) and US (Rituxan®; Genentech) to treat non-Hodgkin's lymphoma (NHL) and chronic lymphocytic leukaemia (CLL).In April 2017 the first biosimilar rituximab (Truxima®; NAPP) was approved in the UK for all indications of the reference biologic. Its adoption is expected to deliver a significant reduction in treatment costs.Administration of rituximab is associated with infusion-related reactions (IRRs). The incidence of IRRs is greatest with the first infusion and decreases significantly with subsequent infusions.To reduce the risk of IRRs, manufacturers recommend that the first dose is gradually increased every 30 minutes in 50mg/hour increments to a maximum of 400mg/hour. For subsequent infusions gradually increase every 30 minutes in 100mg/hour increments to a maximum of 400mg/hour, known as standard subsequent rate infusion. This means a typical rituximab infusion can take 4-6 hours.If the first infusion is well-tolerated, it is now widespread practice to administer subsequent MabThera® doses as a rapid infusion over 90 minutes, whereby 20% of the dose is given over the first 30 minutes, with the remaining 80% over the following 60 minutes (Sehn et al, Blood 2007).Reverting to slower infusion rates with the introduction of biosimilar rituximab could adversely impact daycare unit capacity, nursing resource, appointment length, and patient satisfaction.AimThe aim of our study was to assess the safety of rapid infusion of Truxima® by reviewing infusion related adverse events in patients 1) switching from MabThera® 2) with previous exposure to MabThera® but last dose received over 6 months ago and 3) rituximab naïve patients.MethodIn May 2017 all patients were switched from MabThera® to Truxima® at UCLH, London. Truxima® doses given between 22nd May and 26th July 2017 were identified from the electronic prescribing system (Chemocare®). Infusion-related reactions were noted from nursing infusion records and graded using Common Terminology Criteria for Adverse Events version 4.03.Patients who had been receiving MabThera® as a rapid infusion continued at this rate with Truxima®. Those patients who had received only one prior dose of MabThera® at the standard first dose infusion rate received their first Truxima® dose as a rapid infusion.Patients who had not received MabThera® for over 6 months or were MabThera® naïve, received their first Truxima® dose at the standard first dose infusion rate. If well-tolerated, subsequent doses were given as a rapid infusion.All patients received premedication with paracetamol (acetaminophen) and antihistamine.ResultsTable 1 shows the patient characteristics, MabThera® and Truxima® infusion rates and infusion-related reactions.DiscussionThe results showed that rapid infusion of Truxima® was well-tolerated in all three groups of patients. Additionally, patients switching from MabThera® safely received their first Truxima® dose as a rapid infusion. One patient switching from MabThera® developed tachycardia during their first Truxima® dose at rapid infusion rate; however this patient was able to receive subsequent Truxima® doses with additional glucocorticoid pre-medication without IRRs.Grade 2 or 3 IRRs were observed with 8 first rate infusions (12%) and 4 of the patients have received further Truxima® doses so far. These patients received their next dose at standard subsequent infusion rate with glucocorticoid pre-medication without incident, and 2 of the patients have had further doses as a rapid infusion without an IRR. Updated results will be presented at the ASH meeting 2017.ConclusionThis study is the first reported post-marketing experience of rapid infusion of biosimilar rituximab and showed that patients can be safely switched from MabThera® to Truxima® without reverting to slower infusion rates. In addition patients who tolerated their first infusion rate of Truxima® were able to tolerate a rapid infusion rate with subsequent doses.These findings will facilitate the introduction of Truxima® at centres prescribing rituximab without adversely impacting resource utilisation or patient experience. [Display omitted] DisclosuresCheesman:Roche: Consultancy; Novartis: Consultancy; Napp: Consultancy; Amgen: Consultancy. Ardeshna:ADC Therapeutics: Consultancy; Roche: Membership on an entity's Board of Directors or advisory committees, Other: Conference Expenses, Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees, Other: Conference Expenses. Townsend:Roche: Consultancy.

Chimeric Anti CD-20 Monoclonal Antibody-Rituximab in Refractory Childhood Idiopathic Thrombocytopenic Purpura: An Indian Experience.

The treatment of chronic idiopathic thrombocytopenic purpura (ITP) continues to be a challange. A significant proportion of patients continue to be symptomatic despite all available means of therapy. Recently Rituximab, a chimeric anti CD-20 monoclonal antibody has been shown to be an effective mode of therapy in such patients with an overall response rate of appx 50 %.We studied the efficacy and side effects of this therapeutic modality in 10 children (6 girls) with chronic ITP. The patients belonged to pediatric age group (median age: 9 years, range 4–18 years) with 4 children less than 10 years of age. All the patients were screened for systemic illnesses and different secondary causes leading to thrombocytopenia. They all had been treated with standard therapies using conventional and high dose steroids, ciclosporin cyclophosphamide, vincristine, periodic use of high dose IVIG and splenectomy in 6 patients, but had continued to be symptomatic with recurrent mucocutaneous bleeds and markedly low platelet counts (< 20x 109/L). All patients received intravenous Rituximab at a dose of 375 mg/M2 as weekly dose for 4 consecutive weeks. The infusion related side effects were a few (n= 3) and minor. They included urticarial rash (1) and fever(2) that responded to antipyretics. None of these were severe enough to interrupt the treatment. A complete response was defined as a platelet count > 100 x 109/L, partial response (PR) as count > 50x109/L and a minor response as a count < 50x109/L but without the need of continued treatment. Patients showing no significant rise in platelet count were marked as showing no response. Of the 10 evaluable children, 9 (90%) showed overall response; 4 (40%) showed complete response and 4 (40 %) showed partial response. Two (20%) patients showed minor responses. Patients have been under follow up for last 3 years. The patients with CR and PR have been in remission for longer periods (as much as 150 weeks ).The side effects due to the therapy have been few and very mild. Besides infusional reactions in 3 patients (Transient fever in 2 and mild rash in 1) there were no significant toxicities. No correlation could be found between clinical/laboratory parameters with the responsiveness or the duration of response except that patients showing a higher degree of response continued to be in remission for a longer period as compared to the ones with lesser degree of response. The high percentage of response in our patients as compared to the ones in other studies could be due to the fact that our patients belonged to a younger age group. Probably children show a better response.In conclusion, Rituximab offers a safe and convenient modality of treatment in symptomatic children with refractory ITP. Its use is certainly cost effective even in a developing country in view of the good degree of a sustained response in these refractory patients wherein all modalities of treatment have failed.

Anti-rituximab antibodies in pediatric steroid-dependent nephrotic syndrome.

Rituximab is a chimeric anti-CD20 monoclonal antibody that induces sustained remission in children with steroid-dependent nephrotic syndrome. However, there is no consensus on the optimal regimen and monitoring of rituximab. In other autoimmune diseases, anti-rituximab antibodies (ARA) have been reported in 10-40% of patients, but their clinical relevance remains unclear. In nephrotic syndrome, data are scarce. We report a single-center retrospective study with immuno- and pharmacological monitoring of rituximab treatment in children with frequent relapsing (FR) or steroid-dependent nephrotic syndrome (SDNS). We analyzed the monthly monitoring of 24 children, receiving a dose of rituximab (375 mg/m2) between December 2017 and April 2018 at the Pediatric Nephrology Department of Robert-Debré hospital, Paris. ARA were detected in 7/24 patients (29%), sometimes after the first infusion of rituximab. ARA were present at baseline in two patients previously treated with rituximab. Both displayed no B-cell depletion. ARA were also reported in 5/22 patients during follow-up, with antibodies always detected in the first month following B-cell recovery. An incomplete CD19+CD20- B-cell depletion at M1 (5-25/mm3) and low serum rituximab levels was predictive of developing ARA. The development of de novo ARA during follow-up was not associated with shorter B-cell depletion. This study shows that ARA are frequent in children with FR/SDNS and that close immuno- and pharmacological monitoring may help personalizing rituximab treatment in patients needing repeated injections.

FC 131OFATUMUMAB OR RITUXIMAB FOR CHILDREN WITH STEROID-DEPENDENT NEPHROTIC SYNDROME. A RANDOMIZED CONTROLLED TRIAL

Abstract Background and Aims The chimeric anti-CD20 monoclonal antibody rituximab has been successfully used in steroid-dependent forms of nephrotic syndrome (SDNS) to maintain oral-drug-free remission, but relapses at one year occur in almost half of the patients. Ofatumumab, a fully human anti-CD20 monoclonal antibody, may be superior to rituximab in maintaining remission of SDNS. We compared the efficacy and safety of ofatumumab vs. rituximab in children and young adults with SDNS (NCT02394119) and evaluated the risk of relapse following steroid and calcineurin-inhibitor tapering and withdrawal. Method We randomly assigned 140 children and younger adults (age 2-24 years) with SDNS maintained in remission with steroids and calcineurin-inhibitors to receive intravenous ofatumumab (1.500 mg/1.73 m2; intervention) or rituximab (375 mg/m2; control). Following infusions, oral drugs were tapered and withdrawn. Participants were followed for 24 months. The primary outcome was relapse at one year, defined by protein-creatinine ratio ≥2000 mg/g or &amp;gt;3+ protein on urine dipstick for 3 consecutive days. Cellular and safety data were also assessed. Results At 12 months, 36 patients (51.4%) relapsed in the rituximab arm and 37 (52.8%) in the ofatumumab arm (Odds Ratio [OR] 1.06; 95% confidence interval [CI] 0.55 to 2.06). At 24 months, 46 children relapsed in the rituximab arm (65.7%) and 53 in the ofatumumab arm (75.7%). In both arms, circulating B cell levels declined following treatment and recovered between 3 and 9 months. Higher pretreatment levels and faster recovery after decline of memory B cells predicted relapse. Conclusion In children and younger adults with SDNS, ofatumumab is not superior to the chimeric anti-CD20 antibody rituximab. Immune phenotyping data indicate that anti-CD20 therapies alter the course of the disease by interfering with memory B cell populations and can be used to predict response to anti-CD20 treatment.

Real-world overall response rate and other outcomes related to originator and biosimilar rituximabin patients with chronic lymphocytic leukemia or non-Hodgkin’s lymphoma in the United Kingdom.

e18696 Background: Rituximab is a chimeric anti-CD20 monoclonal antibody therapy, used primarily for treating chronic lymphocytic leukemia (CLL) and non-Hodgkin’s lymphoma (NHL). Rituximab-abbs, the first rituximab biosimilar, was approved in the UK in 2017 and was expected to significantly reduce drug acquisition costs, but there is a lack of real-world evidence regarding patient outcomes with rituximab-abbs. This non-interventional study assessed the real-world effectiveness and tolerability of rituximab-abbs and rituximab in treatment-naive patients with CLL or NHL. Methods: Anonymized data on patient characteristics, response to treatment, healthcare resource utilization and costs were abstracted retrospectively via an online physician survey. UK-registered hematologists and oncologists reported on randomly selected patients aged ³18 years from four cohorts with documented CLL or NHL, who had received rituximab-abbs or rituximab as first-line immunotherapy (between January 1, 2018 and June 30, 2019). Patient outcomes data were provided from first treatment to the last date of follow-up available in the medical records. Results: In total, 46 physicians abstracted data from 201 patient charts. Demographic profiles of the cohorts were similar. For both treatments, the overall response rate (ORR) was very high for patients with CLL or NHL (Table) along with rates for six-month progression-free survival (96–98% across cohorts) and one-year survival (98–100% across cohorts). Most patients did not experience a grade ≥3 adverse event during treatment (54–66% across cohorts); the most common grade ≥3 adverse events were neutropenia, fatigue, anemia and infusion reactions. Healthcare resource utilization was similarly high across cohorts, driven by drug costs, diagnostic testing, oncologist office visits, and day case hospital admissions. Mean annual savings of approximately £1,000 per patient were seen with rituximab-abbs, attributable to first-line treatment costs. Conclusions: The originator (rituximab) and biosimilar (rituximab-abbs) products yielded comparable efficacy and tolerability in treating CLL and NHL in routine UK clinical practice, with rituximab-abbs demonstrating cost-savings. These findings should inform decision-makers on the potential for cost reductions where the biosimilar rituximab-abbs is available as a treatment alternative.[Table: see text]

Fatal Enterovirus-related Myocarditis in a Patient with Devic's Syndrome Treated with Rituximab.

Enteroviruses are a frequent source of infection and among the most common central nervous system viral pathogens. Enteroviruses – in particular, the Coxsackie B viruses – are a known cause of myocarditis. Rituximab is a genetically engineered chimeric anti-CD20 monoclonal antibody. Many reports in the literature suggest a higher risk of infection following repeated rituximab therapy, including viral infection. However, observations of enterovirus-related myocarditis in the context of rituximab treatment are scarce. The authors describe the case of a patient with neuromyelitis optica spectrum disorder who developed severe and fatal enterovirus-related myocarditis after rituximab therapy with a difficult differential diagnosis of autoimmune or giant-cell myocarditis. This case highlights the importance of complete diagnostic workup in difficult cases of myocarditis, including endomyocardial biopsies.

Construction and Characterization of 1F5 Chimeric Anti-CD20 Monoclonal Antibodies: an Efficient Splicing by Overlap Extension-polymerase Chain Reaction Technique

Despite the unparalleled success of anti-CD20-targeted immunotherapy, the currently available mAbs are not sufficiently efficacious in the treatment of lymphoma. 1F5 is one of a panel of anti-CD20 mAbs that was used in the B-cell lymphoma serotherapy. Despite the efficacy of murine 1F5 mAbs in lymphoma patients, the 1F5 chimeric antibodies with human effector functionality are yet to be approved and widely used in the treatment of lymphoma. In this study, the conversion of 1F5 mAb from mouse IgG2a to human-mouse chimeric IgG1 was achieved and the chimeric antibody was partially characterized. We constructed the 1F5 chimeric mouse-human anti-CD20 antibody genes using an efficient Splicing by overlap extension-polymerase chain reaction (SOE-PCR) technique and cloned the chimeric heavy and light genes in pBudCE4.1 mammalian expression vector, followed by purification of the expressed chimeric 1F5 mAbs using affinity chromatography. Our investigation also included the biological properties of purified chimeric antibodies. The generated 1F5 chimeric mAbs mediate complement-dependent cytotoxicity (CDC) and antibody-dependent cellular cytotoxicity (ADCC) against Raji and Daudi Burkitt's lymphoma cell lines, which were comparable with rituximab and exhibit superior reduction in cell viability in vitro, compared to rituximab. The current study indicated that the generated chimeric 1F5 mAbs has potential CDC and ADCC activity which was comparable with rituximab whereas it exhibits a superior reduction in cell viability, compared to rituximab. Our work contributes to future studies involving in vivo biological functions and the application of the 1F5 chimeric antibody.

POS-724 THROMBOTIC MICROANGIOPATHY AND EBV RELATED POST-TRANSPLANT LYMPHOPROLIFERATIVE DISORDER IN A YOUNG PATIENT: A CASE REPORT

Post-transplant lymphoproliferative disorders (PTLD) are recognized as a devastating complication of organ transplantation. In kidney transplants the incidence is estimated between 1 and 2%. They have been closely associated with Epstein-Barr virus (EBV), and the spectrum of manifestations after transplantation range from an infectious mononucleosis-like syndrome to more serious polyclonal or monoclonal lymphoproliferation. Herein we report a case of an EBV associated PLTD in a young patient A 12 years old boy received a paternal renal transplant for kidney failure secondary to Ig A nephropathy in december 2012. They both had old immunity (IgG positif and IgM negatif) to EBV. They had 3 mismatchs and the induction treatment was based on basiliximab, ciclosporin and steroids , the maintenance therapy consisted of ciclosporine, prednisone and MMF Post tranplant complications were marked by the onset of a VZV infection after 2 months which responded well to aciclovir treatment On october 2013, he was admitted to the transplant unit for exploration of an alteration in graft function and thrombopenia ; initlaly he was treated as an acute rejection by solumedrol boli and a biopsy of the graft was performed. The C2 dosage of ciclosporin returned very high being in the zone of toxicity and the result of the biopsy confirming it with the diagnosis of a thrombotic microangiopathy (TMA) secondary to anti calcineurins (ciclosporin) After 1 month , the patient presented episodes of rectal bleeding with gastrointestinal fibroscopy and left colonsocpy returned to normal with fever, earaches and elevated LDH without alteration of the graft’s function A specialized examination was performed objectifying a bilateral sero mucous otitis and we completed with a pelvic thoraco abdomino and cavum CT scan which showed multiple cervical and inguinal lymphadenopathy with nodular splenomegaly and the EVB pcr came back positive We completed with a fine needle aspiration and lymph node biospy diagnosing a lymph node localisation of diffuse large B cell lymphoma . Initial management consisted on withdrawl of immunosuppression and the prescription the chimeric anti-CD20 monoclonal antibody rituximab and transfusion of platelet pellets but the patient presented a severe thrombocytopenia with alteration of neurological condition secondary to meningeal haemorrhage and the result was fatal. Although the induction treatment in our case was based on basiliximab and the patient was Ig G positif to EBV before transplatation , he presented a severe form of an EBV related PLTD.

Efficacy Profile and Safety of Very Low-Dose Rituximab in Patients with Graves' Orbitopathy.

Background: Rituximab (RTX), a chimeric human-murine anti-CD20 monoclonal antibody, has been used for treatment of active moderate-severe Graves' orbitopathy (GO) since 2004 as second-line therapy in patients unresponsive to intravenous steroids. We conducted an open-label prospective study (EUDRACT 2012-001980-53) in which patients were treated with a single infusion of only 100 mg RTX to analyze the efficacy and safety of this low dose. Methods: Seventeen patients, of whom nine had disease that was unresponsive to intravenous methylprednisolone and eight with newly diagnosed GO, were enrolled. Disease activity was assessed with the clinical activity score (CAS) and severity with a composite ophthalmic score. Long-term surgical treatment and quality of life were also assessed, as well as treatment-related adverse events. Results: Mean baseline CAS was 4.56 ± 0.96 and decreased to 1.25 ± 1.14 at 24 weeks (p = 0.001). Disease inactivation occurred within 24 weeks in >90% of patients and was unrelated to disease duration. Severity improved in about 60% of patients, with no relapses. All patients showed peripheral depletion of CD20+ and CD19+ cells at the end of RTX infusion (60 minutes). Two patients required surgical orbital decompression because of optic neuropathy (ON). Among adverse events observed, there was one patient who developed a cytokine release syndrome. Conclusions: A dose of 100 mg RTX is effective in patients with active moderate-severe GO. Low doses are better tolerated, expose patients to immune suppression for a shorter period of time, and are extremely cost effective, compared with higher doses. This dose, consistently with all other immunosuppressants, does not prevent the progression of GO to dysthyroid ON.

Successful Pregnancies in a Patient with Childhood-onset Steroid-dependent Nephrotic Syndrome during Rituximab Maintenance Therapy.

There are an increasing number of reports on the safe use of rituximab (RTX), a chimeric anti-CD20 monoclonal antibody, in pregnant women with hematological malignancies or refractory autoimmune diseases. In 2014, the use of RTX for patients with complicated steroid-dependent nephrotic syndrome (SDNS) was approved in Japan. We herein report a woman with childhood-onset complicated SDNS due to focal and segmental glomerulosclerosis, who had two successful pregnancies while receiving RTX maintenance therapy. No adverse complications were observed during the pregnancies, and she delivered healthy newborns. This case suggested that RTX may be used safely in pregnant women complicated with SDNS.

Rituximab hypersensitivity reactions and tolerance of ofatumumab therapy

B-cell depleting agents play a key role in a variety of disease entities. Rituximab, a murine-human chimeric anti-CD20 monoclonal antibody, as one of these major agents, has been associated with hypersensitivity reactions, which not only include the classic hypersensitivity ranging from immediate (type 1) to delayed (type IV), but also infusion-related reactions (IRRs). Whilst these typical hypersensitivity reactions occur in the setting of prior exposure, IRRs may occur in first exposure. Factors to consider include chimeric composition of agent, for example, rituximab with murine component, which may be responsible for such hypersensitivity reactions. In these individuals, alternate anti-CD20, such as oftatumumab, a fully human monoclonal antibody may be used. We report three cases of rituximab hypersensitivity in patients with auto-immune disease, and in whom ofatumumab therapy was given and subsequently tolerated.

Efficacy and safety of different dosages of rituximab for refractory generalized AChR myasthenia gravis: A meta-analysis

BackgroundRituximab (RTX) is a mouse-human chimeric anti-CD20 monoclonal antibody and has been increasingly used for preventing relapses in myasthenia gravis (MG). However, the appropriate dose for maximizing the beneficial effects in refractory MG with acetylcholine receptor (AChR) autoantibody is a long-standing and critical debating question. MethodsWe performed a meta-analysis to evaluate the efficacy and safety of the different doses of RTX in 260 refractory AChR-MG patients. ResultsThe AChR-MG patients were divided into low or routine RTX dose groups. An overall proportion of 77% (p = 0.000) AChR-MG patients demonstrated improved clinical status as indicated by the Myasthenia Gravis Foundation of America post-intervention scale (MGFA-PIS). There were 77.1% patients showed improved clinical status in lower dose of RTX group (p = 0.000) and 76.8% in routine protocol group (p = 0.000). Although we found there was no significant difference in the proportion of AChR-MG patients with improved clinical status or adverse reactions between the two groups, adverse reactions might be lower in the lower dose RTX group. ConclusionMost of refractory MG patients with anti-AChR autoantibody were well responsive and tolerated to RTX treatment. Repeated application of lower dose of RTX was effective and might be more appropriate for refractory AChR-MG patients with potential lower side effects.

Hydroxychloroquine and COVID-19: can we learn from the use of rituximab in systemic lupus erythematosus?

Rituximab (RTX), a chimeric monoclonal anti-CD20 antibody has become part of the standard therapy for patients with CD20-expressing B-cell lymphoma and rheumatoid arthritis. After encouraging results with open studies in systemic lupus erythematosus (SLE), RTX has not shown its effectiveness in randomized controlled trials. However, its efficacy has been validated in renal, hematological, and neuropsychiatric disorders. Understanding the history of RTX in SLE would be instructive in the hydroxychloroquine (HCQ) saga in COVID-19. Three steps would be necessary and sufficient before definitively closing the debate: 1) determine the effective and safe dose of HCQ, as well as the minimum duration of treatment in COVID-19; 2) define the profile of patients in whom HCQ would be more likely to be effective (especially in asymptomatic patients and/or at the onset of the first signs of the disease) and 3) conduct one or more multicentre RCT to evaluate the efficacy and safety of HCQ in COVID-19 in SSA.

Rituximab Induced Interstitial Lung Disease Diagnosis, Treatment Outcome, and Risk’s Factor, a Place for Transbronchial Pulmonary Cryobiopsy

Rituximab (RTX) is a mouse/human chimeric anti-CD20 IgG1 monoclonal antibody, approved in late 1998 by the FDA. Effectively used as a single agent or combined with a chemotherapy regimen to treat lymphoma, RTX is a significant step forward in the arsenal treatment of idiopathic thrombocytopenic purpura, systemic lupus erythematous, rheumatoid arthritis, and autoimmune hemolytic anemia. Side effects of RTX are commonly seen during the first infusion in up to 50% of patients and include fever, chills, and rigors. These side effects are generally transient and related to the tumor burden, probably due to a greater degree of complement activation and proinflammatory cytokine release. Severe lung toxicity like cryptogenic organizing pneumonia, pneumonitis, and interstitial lung diseases are infrequent, with most of the knowledge coming from case reports.

Ofatumumab or Rituximab for Children with Steroid- and Calcineurin Inhibitor -Dependent Nephrotic Syndrome - &lt;i&gt;A Superiority Randomized Controlled Trial (OFA2)&lt;/i&gt;

Background: The chimeric anti-CD20 monoclonal antibody rituximab has been successfully used in steroid- and calcineurin inhibitor-dependent forms of nephrotic syndrome to maintain oral-drug-free remission, but almost half of patients relapse at one year. Ofatumumab, a fully human anti-CD20 monoclonal antibody, may be superior to rituximab in maintaining remission in these patients. Here, we compared head-to head ofatumumab and rituximab in a randomized controlled clinical trial. Methods: In this single center superiority clinical trial, 140 children and young adults (age 2-24 years) with nephrotic syndrome in remission with steroids and calcineurin-inhibitors were randomized to receive intravenous ofatumumab (1.500 mg/1.73 m2; intervention) or rituximab (375 mg/m2; control). Following infusions, oral drugs were tapered and withdrawn within 60 days. Participants were followed for 36 months. The primary analysis followed an intent-to-treat approach. The primary outcome was relapse at one year, defined by proteinuria (creatinine ratio ≥2000 mg/g). The secondary endpoint included the occurrence of a disease relapse within 24 months from infusion. Cellular and safety data were assessed. Findings: At 12 months, 37 participants relapsed in the ofatumumab arm (52.8%) vs. 36 in the rituximab arm (51.4%; Odds Ratio [OR] 1.06; 95% confidence interval [CI] 0.55 to 2.06). At 24 months, 53 participants relapsed in the ofatumumab arm (75.7%) vs. 46 in the rituximab arm (65.7%; [OR] 1.6 [Cl] 0.8 to 3.3). Analyses stratified by age ≤9 and >9 years supported the same conclusion. Anti-rituximab antibodies did not modify the effects of the intervention. No important side effects occurred during infusion nor during follow up. Higher pretreatment levels of memory and IgM-memory B cells predicted relapse. Interpretation: Ofatumumab is not superior to rituximab in maintaining oral-drug-free remission in children with steroid-and calcineurin inhibitor-dependent nephrotic syndrome. Anti-CD20 antibodies may alter the course of the disease by interfering with memory B cell populations. Clinical Trial Registration Details: Clinical Trials.gov (identifier: NCT02394119) and Eudract.ema.europe.eu (identifier: 2015-000624-28). Funding Information: PR, FL, FM and GMG were supported by the Italian Ministry of Health, Ricerca Finalizzata, grant: WFR:PE-2016-02361576. MC and MV are supported by the Associazione per la Cura del Bambino Nefropatico ONLUS. GMG, MB, and MC are supported by ‘’Fondazione Malattie Renali del Bambino” ONLUS. The Institute Giannina Gaslini (trial sponsor) provided logistic and financial through grant ‘Cinque per mille of IRPEF-Finanziamento della ricerca sanitaria’. The funder had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. Declaration of Interest: Authors declare no competing interests. Ethical Approval: We obtained study approval from the local Independent Ethics Committee (ComitatoEticoRegione Liguria), the Italian Drug Agency (AgenziaItaliana del Farmaco, AIFA).

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

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

Clinical Relevance of Polymorphonuclear Myeloid-Derived Suppressor Cells in Autoimmune-Blistering Disorders Pemphigus Vulgaris and Bullous Pemphigoid

Clinical Relevance of Polymorphonuclear Myeloid-Derived Suppressor Cells in Autoimmune-Blistering Disorders Pemphigus Vulgaris and Bullous Pemphigoid