Skin Reactions ‘Frequent’ With Mavenclad, Real-world Study Finds

Skin reactions are common among relapsing-remitting multiple sclerosis (RRMS) patients being treated with oral Mavenclad (cladribine), affecting about one-third of the people evaluated in a real-world study in Germany.

These findings suggest the need for careful clinical surveillance to rapidly diagnose and possibly treat skin problems stemming from Mavenclad’s use, its researchers noted.

The study, “Skin reactions in patients with multiple sclerosis receiving cladribine treatment,” was published in Neuroimmunology & Neuroinflammation.

Mavenclad, an oral disease-modifying therapy developed by EMD Serono (Merck KGaA outside of the U.S. and Canada), is approved to treat RRMS and active secondary progressive multiple sclerosis (SPMS). The treatment is given in two courses over two years, with each course consisting of two four-to-five day cycles, spaced one month apart.

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Common side effects of Mavenclad treatment include headache, the common cold, and low white blood cell counts, which can increase the risk of infections, including those of herpes zoster (shingles) and herpes simplex (cold sores).

Skin-related side effects, including rashes and hair loss, have also been reported. But they “are not mentioned in the risk management plans” of multiple sclerosis (MS), the research team wrote.

Investigators sought to determine the frequency of skin reactions following Mavenclad treatment in a real-world setting. They examined 239 RRMS patients, with a median age of 40, who were receiving the therapy for a median of 23.7 months (about two years).

Overall, 77 (32%) patients developed at least one skin reaction after a Mavenclad treatment course.

Acute skin reactions — those occurring within the first three months following a treatment course — were the most common, found in 54 (23%) patients. These reactions included hair thinning, skin rash, inflammation of the mucous membranes lining the mouth or gut (mucositis), and itchy skin (pruritus).

Herpes virus infections were also observed in 15% of patients (35 people) a median of 83 days (almost three months) after the last treatment course. These infections tended to appear in people with low white blood cell levels. Most of the patients with herpes zoster infections had severe infections, and required hospitalization.

Another 3% of patients had delayed skin reactions, or those that developed more than three months after a last Mavenclad course. These included three cases of acneiform rash (acne-like bumps), two cases of alopecia areata (hair loss), one case of hair thinning, and one case of leukocytoclastic vasculitis (inflammation of small blood vessels).

According to the researchers, delayed alopecia areata and leukocytoclastic vasculitis may represent secondary autoimmune complications of Mavenclad treatment.

“In light of the observed delayed skin reactions, we further emphasize the necessity of careful clinical surveillance of cladribine [Mavenclad]-treated patients for yet undescribed secondary autoimmune events,” they wrote.

Skin carcinomas (cancers arising in the tissue lining the outer surface of the skin) or precancerous lesions (a group of cells that look abnormal and are likely to progress to cancer) were reported in two patients. Another developed squamous cell carcinoma, a type of skin cancer, and stopped the treatment.

The rate of cancerous and precancerous lesions seen here, the study noted, is similar to that observed in clinical trials of Mavenclad.

This study demonstrated “that skin-related AEs [adverse events] are frequent” with Mavenclad’s use, its researchers wrote, although “most cases of acute reactions resolved without specific treatment while cladribine was continued.”

Still, “a complete clinical examination of the skin at regular intervals should be mandatory for all patients,” they concluded.