Towards the successful treatment of dermatomyositis

Dermatomyositis (DM) is a rare autoimmune disorder of unknown cause that affects about 20 – 90 people per million globally1. Until recently, those living with the disease in the USA mostly relied on off-label medications but, on 16 July 2021, the US Food and Drug Administration (FDA) approved – Octapharma’s intravenous immunoglobulin (IVIg) therapy 10% – for use by adults with DM. Further approvals followed in Europe and around the world.

“Patients with DM, especially those with refractory disease, had a poor prognosis and suffered from lack of approved treatment options,” recalls Rohit Aggarwal, MD MS, Medical Director of the Arthritis and Autoimmunity Center at the University of Pittsburgh School of Medicine, USA, adding: “When Octapharma took a bold leap to pursue the possibility of IVIg treatment options for DM, I felt it was a great opportunity to use my expertise to help advance the field.”

Dr Aggarwal, an internationally recognised expert on myositis, was a member of the Advisory Board who discussed the Progress in DERMatomyositis (ProDERM) study’s design before becoming a member of the Study Steering Committee and sub-investigator for the phase III clinical trial.

The ProDERM study: IVIg to treat DM

The intention of the ProDERM study was to evaluate the efficacy, safety and long-term tolerability of IVIg in patients with DM. Back in 2016, when Board Member Wolfgang Frenzel, responsible for R&D at Octapharma, first asked Irene Beckmann, Global Clinical Project Manager for Immunotherapy, to lead the study, she was immediately eager to start work, recognising that DM represented a huge unmet need. “I felt both excited and really happy to lead the ProDERM team. I knew it would be a challenging project, but I was not afraid of that. And what truly motivated me was that it was clear from the start we were principally doing it for the patients,” says Irene.

Patients with DM (usually adults in their late 40s to early 60s, but also children between the ages of five and 15) commonly suffer from skin rashes, chronic muscle inflammation and progressive muscle weakness. Complications can include difficulty swallowing, aspiration pneumonia, breathing problems and calcium deposits on muscles, skin and connective tissues.

Critical patient participation

After gaining FDA approval of the protocol, and subsequent wider approval by other national authorities, the study enrolled 95 patients from 36 sites in 10 countries. “The design of the ProDERM study, allowing patients to switch treatment if they deteriorated, facilitated recruitment of a large number of patients for such a rare disease,” explains Dr Aggarwal.

Terézia, a 65-year-old retired former civil servant from Budapest in Hungary, and József, a 42-year-old Hungarian lorry driver and sports fanatic, both took Octapharma’s IVIg therapy. “I was not scared at all,” recalls Terézia. “The doctors provided me with a good amount of detailed information about the treatment. I also had great support from my family who encouraged me – because it could make a difference to my life.”

When Terézia first experienced symptoms of DM at the age of 33, she saw a range of doctors, including a rheumatologist, but none of them could find an underlying cause. Many linked her skin rashes and hair loss to an allergy. “I was constantly tired. I couldn’t lift my arms, indications which I now know are typical of the disease appeared on my fingers, and I lost weight suddenly, dropping from 54 to 44kg. I could not sit up from lying down – the muscles around my shoulders and in my upper arms were severely inflamed and ‘deflated’.” Terézia’s health was worsening, and her family was beginning to lose hope until a professor of dermatology made a conclusive diagnosis.

József was diagnosed in 2014. “I was originally misdiagnosed and treated by the Department of Dermatology,” he remembers, adding: “When we finally learned what my disease was, it was obviously hard for me and my family and it proved to be an ongoing challenge – physically, mentally and financially.”

Unfortunately, misdiagnosis is common. Dr Aggarwal explains: “Diagnosis of DM can often be confused with other autoimmune disorders such as lupus or psoriasis if physicians have not already encountered it, and patients usually have to undergo a series of tests and procedures to be certain.”

As his condition progressed, József’s life changed radically. Basic everyday tasks such as sitting, walking and swallowing became difficult. “When I started IVIg treatment, I could climb one step again and I could swallow. Since then – because I was mentally positive and did everything I physically had to do – my condition has been gradually improving.”

Treatment of DM with octagam® 10% now likely worldwide

IVIg is a concentrated solution of antibodies derived from donated human plasma. While it has been used to treat a variety of autoimmune diseases for decades, its use in DM and for myositis generally was, until summer 2021, off-label in Europe and the USA. “Now, however, with the approval we have gained as a result of the study, we have given a treatment option and renewed hope to our DM patients,” explains Irene.

It is a result everyone had been eager to see. “All the physicians and researchers involved were keen to make the study successful. I think we all saw the obvious need for IVIg for these patients and understood what it would mean for their lives,” recalls Irene.

Zoltan Griger MD PhD, Division of Clinical Immunology, Faculty of Medicine, University of Debrecen, Hungary, another member of the Advisory Board and sub-investigator in the ProDERM study, shares a similar view: “The ProDERM study has given patients hope. You can see it in their eyes. One patient told me that, as she put it, life can take everything away from you in the blink of an eye – material things, your loved ones, your health – but not your faith or your willpower to be able to start over.

“Since the trial, she has felt a sense of renewed strength, which is allowing her to write and paint, and to feel fully alive again,” Zoltan recalls, adding: “It is not about the milestones or the innovation; it is about improving the lives of patients.”

References

1. Orphanet: Dermatomyositis