Aubagio Safely Used by 5 MS Patients With Active COVID-19 Infection

Five people with multiple sclerosis (MS) who tested positive for COVID-19 while being treated with Aubagio (teriflunomide)  all developed a mild infection, had good outcomes, and experienced no disease relapses, a case study reported.

These findings suggest that use of Aubagio, a disease-modifying therapy that acts on the immune system, does not need to be paused when patients are infected with the new coronavirus strain, its scientists wrote.

Their report “COVID‑19 in teriflunomide‑treated patients with multiple sclerosis” was published as an “original communication” in the Journal of Neurology.

Managing MS usually requires long-term immunotherapy to control the immune-mediated inflammation that damages myelin — an insulating sheath around nerve cells. Currently, almost 20 disease-modifying therapies (DMTs) are approved by the U.S. Food and Drug Administration to treat MS.

Evidence suggests that DMTs which modulate the immune system can make people more prone to infection, and a possibility of repeat hospitalizations and poorer outcomes.

For these reasons, the current pandemic raised concerns among MS patients and their physicians of a viral infection risk. A number of specialists suggested that DMTs with higher immunosuppressive actions be discontinued in the case of an active COVID-19 infection in a patient.

Yet, stopping a therapy can pose a risk of MS reactivation or relapse, the study noted.

Researchers at the Brigham and Women’s Hospital described five cases of MS patients using Aubagio — an approved oral therapy for relapsing forms of MS, marketed by Sanofi — with an active COVID-19 infection. All were taking Aubagio for at least six months prior to the viral infection, and continued with the treatment at their prescribed dose.

“Managing MS during the COVID-19 pandemic has raised many questions,” Rohit Bakshi, MD, a senior neurologist at the Boston hospital and the study’s lead author, said in a press release. “Our observations in these five patients suggest that teriflunomide may not need to be discontinued in patients with MS who develop an active COVID-19 infection.”

The first was a 52-year-old man who began treatment with Aubagio in 2017, upon disease diagnosis. In addition to MS, he was diagnosed with obstructive sleep apnea, hyperlipidemia (high cholesterol), attention deficit hyperactivity disorder, and depression. After starting on Aubagio, he showed no signs of disease progression on MRI scans.

His COVID-19 symptoms — severe fatigue, headache, nasal congestion, and loss of a sense of smell — started on March 20.  Two days later, he developed myalgia (muscle pain), fever and rigors (shivering), rhinorrhea (runny nose), and diarrhea, but had no further respiratory symptoms, like cough or shortness of breath.

A COVID-19 test given on March 22 confirmed his positive status, and he was advised by his neurologist to continue using Aubagio at the same dose while self-isolating at home. Thirteen days after COVID-19 symptom onset, an examination found no neurological or respiratory symptoms, other than a continued inability to smell.

About a month later, 25 days after the infection’s onset, the patient returned to a normal life and reported his sense of smell slowly returning.

A 52-year-old woman diagnosed with relapsing-remitting MS (RRMS) in 2002 is the report’s second patient. She began treatment with Aubagio in October 2016, and her MS was determined to be stable with mild disability. She had no comorbidities (co-occuring disorders).

The woman developed COVID-19 symptoms — headaches, nausea and vomiting, mild fever, asthenia (severe weakness, lack of energy), and loss of sense of smell — on March 10. Five days later, she tested positive for the coronavirus. Her neurologist also advised her to continue using Aubagio at her current dose.

She was monitored at home via telemedicine, and began to recover 15 days after infection onset. By the end of March, the woman had completely recovered.

The third patient, a 47-year-old man diagnosed with RRMS in 2015, was taking Aubagio since 2016 and had stable disease. On March 20, he reported COVID-19 symptoms, including a sore throat lasting three weeks, diarrhea, and a low-grade fever, cough, and mild shortness of breath that had begun days earlier.

He tested positive for COIVD-19 that same day, and quarantined at his home while continuing with Aubagio for his MS.

The man’s symptom gradually improved, the researchers wrote, and on April 28 his resumed his normal life — including running five miles daily.

A 38-year-old homeless man, diagnosed with RRMS in 2009 and with a history of attention deficit disorder, anxiety, and alcohol abuse, was the next patient.

The man began treatment with Aubagio in November 2019 after years of no MS therapy, and the discovery of a brain lesion and multiple lesions in the spinal cord on MRI scans. He was tested and found positive for COVID-19 on April 16, with a low-grade fever and dry cough evident. His symptoms “rapidly improved over the following days,” the researchers reported, and his Aubagio dose was maintained.

The fifth patient was a 79-year-old woman diagnosed with RRMS in 1992 with disease worsening (exacerbations) in 2008 and 2012, when she was determined to have to secondary progressive MS (SPMS). Her medication was switched from interferon beta-1a to Aubagio in September 2017, and her disease stabilized.

She was hospitalized in intensive care from March 30 to April 2 for a serious bacterial infection, and her MS treatment was  interrupted for 12 days. She resumed using Aubagio at her recommended dose, every other day, on April 15. That same day, she complained of a sore throat and low-grade fever, and tested positive for COVID-19 infection.

Viral symptoms resolved over the next eight days while she continued with her Aubagio treatment, the study noted.

Severe COVID-19 infections are usually characterized by a cytokine storm and an uncontrolled immune response against the virus that causes more damage to tissue. Aubagio’s mechanism of action may help to prevent this type of anti-viral response, the researchers suggested, and could have contributed to the favorable outcomes in each of these five COVID-19 cases.

Aubagio also leads to a drop in the proliferation of both T-cells and B-cells, two types of immune cell  involved in MS, they wrote. Yet this inhibition does not cause these cells to die, allowing for the immune system to fight infections.

Unlike other DMTs, Aubagio lowers the level of immune activation without major immunosuppression, which may help to prevent the exaggerated immune response seen in the most severe COVID-19 cases, the researchers suggested.

“One possible beneficial effect of teriflunomide in the face of COVID-19 may be to prevent an excessive/fulminant host immune response, while maintaining an adequate defense against the virus,” they wrote.

“Our observations suggest that teriflunomide may not need to be discontinued in patients with MS who develop an active COVID-19 infection” they added.

Due to the small number of cases detailed here, however, they recommended further studies to validate these findings.

“A delicate balance may be necessary in the host immune response to successfully confront COVID-19 infection,” Bakshi said. “Additional studies are warranted to further understand the relationship between treatment with teriflunomide and outcomes for MS patients with COVID-19.”