Progressive MS Patients with Considerable Disability Ably Treated with Cladribine, UK Case Study Reports

Cladridine may be effective in preventing disability progression and reducing damage to nerve cells in people with progressive forms of multiple sclerosis (MS), researchers suggest based on a case study of two such patients given the injectable treatment.

MS is characterized by progressive degeneration of cells in the central nervous system, mostly due to an impaired immune response and inflammation. The disease can be progressive from onset, identified as primary progressive MS or PPMS. But most patients are diagnosed with RRMS and — after a period of relapses and remissions that can last about 10 years — transition to secondary progressive MS or SPMS.

Eleven different classes of disease-modifying therapies (DMTs) are currently approved in Europe and the U.S. to treat MS, but only Ocrevus (ocrelizumab) has been approved to treat progressive MS, with its use largely restricted to PPMS patients.

This highlights the urgent need for DMTs that can effectively treat progressive disease forms.

In the study “Disease activity in progressive multiple sclerosis can be effectively reduced by cladribine,” researchers at the Blizard Institute, part of Queen Mary University of London, detailed two progressive MS patients who they treated off-label with cladribine injections. The study was published in Multiple Sclerosis and Related Disorders.

Cladribine, marketed under the name Mavenclad by EMD Serono (Merck KGaA outside the U.S. and Canada), is approved as an oral treatment for relapsing MS in Argentina, Canada, Australia, Israel, Europe, and United Arab Emirates.

The first case involved a man of Asian ascent who had been diagnosed with relapsing MS at age 21, with unilateral inflammation of the optic nerve as the initial disease manifestation.

He was treated with Rebif (interferon beta-1a), but stopped that treatment after two years because it failed to prevent his relapses. For the next nine years, he went without treatment despite a high relapse rate. His condition progressed significantly, showing moderate disability (EDSS 4.0) with a significant brain lesion burden.

At this point he started using Tecfidera (dimethyl fumarate), but decided to stop after three weeks due to side effects that included fatigue, flushing, and abdominal discomfort.

A detailed analysis of his disease course now showed chronic deterioration had started around six months ago, indicating the man had entered the SPMS stage. In 18 months, his EDSS scores — which quantify disability and its progression over time— rose from 4.0 to 6.0 (severe disability), and had a nearly 4.5-fold higher levels of neurofilament light chain (NfL) determined from cerebral spinal fluid (CSF) sample. Levels of NfL, a protein, is being investigated as a biomarker of nerve cell damage in MS.

One month later, doctors decided to start treating him off-label with subcutaneous (under-the-skin) cladribine, sold under the brand name Litak (approved to treat hairy cell leukemia). He was treated on a schedule of  cladribine 10 mg injections for three days on weeks one and five.

The second case concerned a woman experiencing progressive weakness in left her leg beginning at age 43. Medical evaluation revealed brain lesions and brain volume consistent with demyelinating disease.

Two year later, her disability had worsened, and her EDSS score was 5.5 (a level at which walking aids are needed for any distance). Laboratory analysis found such high levels of NfL in her CFS sample that were “off the scale” — more than 26 fold — and beyond accurate quantification).

Her medical team began treating her as well with cladribine injections on a similar treatment schedule.

Cladribine was well-tolerated, with no adverse reactions being reported on follow-up visits. Both patients experienced significant reduction in inflammation and disease activity, as determined by brain magnetic resonance imaging (MRI) scans and by a drop in NfL levels of 73% in the man, and 80% in the woman.

The man showed mild disability progression while on cladribine, with his EDSS moving from 6.0 to 6.5 in one year; disability in the woman remained stable.

Supported by these positive outcomes, the researchers suggest that progressive MS patients “with detectable disease activity (MRI, elevated NfL) should be considered for DMTs.”

And, they added: “Over and above its licensed indication (relapsing MS), cladribine may be an effective treatment option” for these patients.

The team also suggested that NfL levels can be “a sensitive index of treatment effect” in progressive MS, and “may be a useful outcome in clinical trials targeting this patient group.”