Off-label Adalimumab May Be of Benefit for Cardiac Sarcoidosis

[Joachim]

Adalimumab — a medication that blocks the pro-inflammatory TNF-alpha protein — safely and effectively eased symptoms of cardiac sarcoidosis in seven adults, allowing them to reduce or discontinue their use of corticosteroids, a study reports.

The therapy also promoted a rise in the number of lymphocytes, a type of white blood cell, which was too low before treatment. Lymphopenia, or having too few lymphocytes in the blood, is a common finding in people with active sarcoidosis and can increase their risk of infections.

Future, appropriately controlled clinical trials “are warranted to determine the safety and efficacy of adalimumab in patients with cardiac sarcoidosis and the mechanisms of improvement of lymphopenia after adalimumab therapy,” researchers wrote.

The report, “Adalimumab in the treatment of cardiac sarcoidosis: Single center case series and narrative literature review,” was published in Respiratory Medicine Case Reports.

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In sarcoidosis, an abnormally active immune system leads to the formation of small clumps of inflammatory immune cells, called granulomas, in different tissues and organs, ultimately affecting their function.

About a quarter of sarcoidosis patients are estimated to have heart involvement (cardiac sarcoidosis), with about 5% of patients developing symptoms. The accumulation of granulomas in the heart may lead to irregular heartbeat or less-efficient blood pumping.

Steroids, also known as corticosteroids, are the first line of treatment for cardiac sarcoidosis and other types of sarcoidosis. They work by reducing inflammation and preventing further tissue and organ damage.

However, if taken for too long or in very high doses, they may cause unwanted side effects such as weight gain, mood changes, and difficulty sleeping.

A previous study showed that about 10% of sarcoidosis patients in the U.S. are being treated with off-label TNF-alpha inhibitors. These work by suppressing the activity of TNF-alpha, a pro-inflammatory molecule implicated in chronic swelling and inflammation, as well as granuloma formation, in sarcoidosis.

One such medication is adalimumab, sold as Humira by AbbVie, with biosimilars also available. It is approved for rheumatoid arthritis, an autoimmune disease that causes the joints to become inflamed and swollen, and several other autoimmune diseases.

Infliximab, sold as Remicade and biosimilars, is the TNF-alpha inhibitor most commonly used off-label in sarcoidosis patients. Previous studies have demonstrated the “benefit of using adalimumab in patients who developed adverse events to infliximab in sarcoidosis,” the researchers wrote.

Our small case series describes favorable safety, tolerability, and efficacy profiles of adalimumab in patients with cardiac sarcoidosis

Medical records examined of 7 adults with cardiac sarcoidosis given adalimumab

Now, a team of researchers in the U.S. and in Jordan looked back at the medical records of five women and two men, ages 54–73 years, with cardiac sarcoidosis who were treated with adalimumab at the University of Illinois Hospital between 2011 and 2022.

Patients received under-the-skin injections of adalimumab (40 mg) once a week as third-line therapy. All were being treated with corticosteroids and methotrexate, an immunosuppressant. One woman was also on, or had received, the immunosuppressant mycophenolate.

Five patients also showed lung involvement, one of whom had additional skin involvement; one patient showed no extra-heart involvement. They experienced a range of symptoms related to the heart, such as shortness of breath, palpitations, and fainting or a feeling they were about to faint.

Results showed that “clinical responses to adalimumab were universally positive,” the team wrote. During the time of treatment, no patient experienced arrhythmias (irregular heartbeats) or was admitted to the hospital. They also did not experience disease symptoms in any other organ.

Six of the seven patients underwent positron emission tomography (PET) scanning of the heart before and after the start of adalimumab treatment. Four patients showed a complete resolution of signs of cardiac sarcoidosis, while the other two had partial resolution.

Importantly, five patients were able to discontinue corticosteroids, while the remaining two patients reduced their dose.

Treatment with adalimumab was generally well-tolerated, with no side effects reported.

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In addition, while all patients showed reduced lymphocyte counts before adalimumab treatment, the therapy led to a significant increase, by about twofold, in the number of circulating T-cells and B-cells, two types of lymphocytes.

While the mechanisms behind this effect remain unclear, it’s possible that adalimumab may prevent the trafficking of T-cells and B-cells from the blood to the site of granuloma formation, potentially easing the disease, the researchers noted.

“This is of particular value in light of the challenging nature of cardiac sarcoidosis treatment,” the researchers wrote.

Still, “such a hypothesis is speculative and requires large randomized controlled trials with a mechanistic arm to identify the actual role of TNF … in regulation of granuloma formation and resolution in various sarcoidosis [types],” they added.

“Our small case series describes favorable safety, tolerability, and efficacy profiles of adalimumab in patients with cardiac sarcoidosis,” the team wrote, adding that “our observation further warrants large prospective studies to evaluate the safety and efficacy of adalimumab in the treatment of cardiac sarcoidosis.”

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