Autoimmune Complications Associated with Lemtrada Solved Using Anti-CD20 Therapies, Case Studies Suggest

Relapsing-remitting multiple sclerosis (RRMS) patients treated with Lemtrada (alemtuzumab) may develop additional (secondary) autoimmune reactions.

Anti-CD20 therapies, including rituximab or Ocrevus (ocrelizumab), are a potential treatment for Lemtrada-associated autoimmune complications in patients who fail to respond to other conventional immunotherapies, according to a case report about two women in Australia.

The study, “B cell depletion therapy resulting in sustained remission of severe autoimmune complications following Alemtuzumab treatment of Multiple Sclerosis,” was published in the journal Multiple Sclerosis and Related Disorders.

Sanofi Genzyme’s Lemtrada is a humanized monoclonal antibody used to slow disease progression in adult patients with RRMS. Lemtrada works by blocking the activity of CD52, a protein found on the surface of immune cells, inactivating them and reducing neuroinflammation associated with MS.

However, despite being highly effective, Lemtrada is linked with a greater risk of developing secondary immune diseases within seven years post-treatment. Evidence suggests that the antibody-mediated targeting of immune cells (like B-cells) can give rise to an abnormal proliferation of B-cells that damage patients’ own cells and tissues.

Pharmacovigilance (monitoring) programs are ongoing to analyze Lemtrada’s risks, however, there are no guidelines to support patients’ treatment when they present with secondary autoimmune disease.

Researchers from Australia shared two cases of women with RRMS who were treated with Lemtrada, then developed additional autoimmune reactions, and were resistant to standard immunotherapy.

The first patient, a 34-year-old woman, was diagnosed with RRMS in 2004. She was treated first with Novartis’ Gilenya (fingolimod) in January 2015, and moved to Lemtrada in November 2015. In August 2017 she developed an immune reaction against factor VIII – the clotting factor whose levels are defective in people with hemophilia — and was diagnosed with acquired hemophilia A that did not respond to classic anti-inflammatory therapy, namely prednisolone.

The poor coagulation and bleeding accompanied by severe hip joint pain led the patient to agree to a treatment with rituximab, an antibody — marketed under the name Rituxan in the U.S., and MabThera in Europe — that targets the CD20 protein at the surface of immune B-cells. By July 2018, levels of factor VIII inhibitors were undetectable, and autoimmune disease was declared in complete remission. No further rituximab was administered.

The second patient was a 20-year-old woman diagnosed with RRMS in early 2014. After significant clinical MS progression, in August 2016 she began treatment with Lemtrada. Within nine months (May 2017), she developed autoimmune hypothyroidism (when the thyroid gland does not produce enough hormones), but went forward with a second round of Lemtrada in November 2017.

In March 2018, after developing immune-mediated thrombocytopenia (low platelet levels) that responded to corticosteroid treatment, the patient showed signs of inflammation of the brain (encephalitis) triggered by an autoimmune response. This caused the patient to have seizures and develop epileptic symptoms that required intubation and ventilation. Despite corticosteroids (anti-inflammatory agents), seizures and neurological function worsened.

She was prescribed two rounds of Genentech’s Ocrevus, also an anti-CD20 monoclonal antibody, at a dose of 300 mg. After treatment, the patient recovered and remained asymptomatic without signs of active autoimmune encephalitis as assessed by magnetic resonance imaging.

The team considered that the autoimmune reactions in both RRMS patients were caused by an abnormal proliferation of B-cells as a result of Lemtrada treatment.

Based on the results, the team suggested that “B-cell depletion therapy should be considered early in the treatment course of patients presenting with severe…autoimmune complications of alemtuzumab [Lemtrada],” and that “clinicians should remain vigilant when caring for patients undergoing alemtuzumab treatment,” they wrote.

While both patients failed to respond to treatment with conventional immunotherapies, anti-CD20 therapies resulted in remission of secondary autoimmune diseases.

Overall, the findings support the use of “anti-CD20 therapy as a potential treatment option in patients with autoimmune complications of alemtuzumab that are postulated to arise as a result of B-cell hyperpopulation,” the team concluded.