rituximab (Rituxirel / Toritz)

ABCD-Trial: study protocol for a randomized, double-blind, placebo-controlled study in patients with Amyotrophic lateral sclerosis for the evaluation of efficacy and safety of B-Cell Depletion with rituximab (ABCD).

Ufer Friederike F, Rössling Rosa R, Spottke Annika A, Németh Robert R et al.

The exact disease-causing mechanisms in ALS remain incompletely understood. A possible cause is inflammation of neurons. Compared to other neurodegenerative diseases, neuroinflammation is pronounced in ALS, presumably leading to disease progression and neuronal death. Patients with ALS can have neuronal autoantibodies and most notably antibody-producing cells in the cerebrospinal fluid. The CD20-binding therapeutic antibody rituximab targets these antibody-producing B-cells. Rituximab is a medication commonly used in neurology. Single patients with ALS have already been treated with rituximab, which was well tolerated. We therefore want to evaluate safety and efficacy of a treatment with rituximab in ALS patients in a double-blind placebo-controlled trial. With this trial we aim for slower disease progression and unveiling disease-causing mechanisms in ALS. A total of 52 male and female patients older than 18 years with active sporadic ALS and disease duration of less than 24 months who are on a stable dose of riluzole (50 mg BID) should be included. Patients requiring assisted ventilation of any kind or have a known intolerance to the study medication rituximab are excluded. The study medication rituximab or placebo should be administered over a period of 52 weeks at 4 distinct time points, followed by a follow-up period of 79 weeks with 4 visits. Treatment efficacy should be evaluated using the ALS functioning scale ALSFRS-R-SE at every study visit (except safety visits). Safety will be assessed through regular laboratory analyses, adverse event (AE) and serious adverse event (SAE) monitoring, and CD20+ B-cell kinetics. The primary endpoint is the change in the ALS Functional Rating Scale-Revised (ALSFRS-R-SE) from baseline to week 79. Trial sites will be at Charité/DZNE Berlin and DZNE Bonn. ALS is a rapidly progressive neurodegenerative disease with limited treatment options. Recent preclinical in vivo studies suggest that B-cell-mediated autoimmunity contributes to disease progression. This trial will evaluate whether rituximab, which specifically depletes CD20+ B-cells, can slow ALS progression and provide insights into disease mechanisms. The trial was registered in the German WHO-recognized primary register Deutsches Register Klinische Studien DRKS (German Clinical Trials Register) on 3/07/2023 under registration number DRKS00030948.

Progressive hemifacial atrophy, AQP4-positive NMOSD and suspected Sjögren's syndrome: five-year relapse-free follow-up during rituximab therapy.

Liu Yan Y, Song Siyuan S, Feng Xiaochao X, Yang Shilin S

Staged multi-target therapy for anti-MDA5-positive dermatomyositis-associated rapidly progressive interstitial lung disease: a case report.

Zhang Lvdan L, Jiao Mengwen M, Hou Yan Y, Jie Youchen Y et al.

Anti-melanoma differentiation-associated gene 5 antibody-positive dermatomyositis-associated rapidly progressive interstitial lung disease is associated with acute respiratory deterioration and high mortality. A man in his 40s presented with fever, dry cough, progressive dyspnea, mechanic's hand-like lesions and severe hypoxemic respiratory failure. Chest high-resolution computed tomography demonstrated rapidly progressive bilateral ground-glass and reticular opacities. Myositis-specific antibody testing showed strong anti-MDA5 positivity, with concomitant anti-EJ, anti-TIF1γ and anti-Ro52 positivity. Initial intravenous methylprednisolone at 80 mg/day produced limited improvement. Early multi-target escalation included divided-dose methylprednisolone, tofacitinib, short-course intravenous immunoglobulin, Pneumocystis jirovecii prophylaxis and an individualized reduced-dose rituximab regimen consisting of 200 mg followed by three weekly 300-mg infusions. Mycophenolate mofetil was briefly withheld during acute escalation and subsequently resumed for maintenance. Oxygenation improved within 48 h, and serial imaging demonstrated progressive regression of the pulmonary abnormalities. During approximately 6.5 months of follow-up, the patient remained clinically stable without a detected serious opportunistic infection. Because several interventions overlapped and rituximab has a delayed immunological effect, the early response cannot be attributed to rituximab alone. This case illustrates the potential clinical value of staged multi-target treatment adjustment and infection-risk management in severe anti-MDA5-associated rapidly progressive interstitial lung disease.

Off-Label Use of Monoclonal Antibodies in Developing Countries.

Alizadeh Bengar Fatemeh F, Mahmoudi Parinaz Sadat PS, Khalili Hossein H

Rituximab was widely used in clinical practice; however, its implementation protocols and safety-monitoring practices varied considerably. In light of these findings, it is important to distinguish between off-label use and inappropriate use, and to ensure that treatment decisions are evaluated against current evidence, clinical guidelines, and indication-specific criteria.