Julie J Paik, MD, MHS: Inflammatory Myopathy in Systemic Rheumatic Diseases

Rheumatology Network interviewed Julie J Paik, MD, MHS, to discuss her Congress of Clinical Rheumatology (CCR) East presentations “Clinicoserological Spectrum of Inflammatory Myopathy in the Context of Systemic Rheumatic Diseases” and “Can Autoantibody Profiles Predict Myositis Phenotype and Disease Course?” Paik is Assistant Professor of Medicine and Director of Clinical Trials at Johns Hopkins Myositis Center, Division of Rheumatology.

Rheumatology Network: Can you give me some of the key takeaways of your spectrum of inflammatory myopathy in rheumatology presentation?

Julie J Paik, MD, MHS: I highlighted key pearls about how to classify different subgroups of myositis, which then enables clinical providers to better subset these diseases. Sometimes, when someone comes in with weakness, you're thinking about a lot of differential diagnoses. But when you divide up the different types of myositis into distinct subgroups, it's better to have a plan of attack in terms of treatment and diagnosis So, I went over the key subgroups: dermatomyositis, polymyositis, immune-mediated necrotizing myopathy, and inclusion body myositis.

Then within each subgroup, I embedded in cases and went through how to approach the diagnosis. What are some of the key clinical features we should be aware of? What is the treatment algorithm for each subgroup? How do I treat this patient? And then I added in a layer of the emerging treatments and promising clinical trials in each subgroup. I also mentioned a clinical trial in immune-mediated necrotizing myopathy. There are, unfortunately, no clinical trials in inclusion body myositis where there's any data that can be read as positive results. Inclusion body myositis is difficult because there's no like treatment for it. I talk largely about dermatomyositis because there are a lot of a lot of pipelined clinical trials and drugs that are in development right now.

RN: Can you speak a little bit more about some of those pipeline trials that you discussed?

JP: It’s an exciting time for dermatomyositis because we have the first FDA-approved drug for dermatomyositis ever that is efficacious, which is intravenous immunoglobulin, as of July 2021. It should be easier for rheumatologists to prescribe it now because there's an FDA indication.

Another promising pipeline drug and promising treatment that I discussed was a phase 2/3 clinical trial of ravulizumab. It's a C5 inhibitor, a complement inhibitor, and the trial is about to start very soon. It's a multicenter, international trial of a complement inhibitor in adult dermatomyositis patients.

I was the principal investigator on a proof-of-concept study of a JAK inhibitor in refractory dermatomyositis or tofacitinib. There are ongoing phase 2 studies internationally looking at a JAK inhibitor in dermatomyositis based on some of the work that we've done that showed a very good response of JAK inhibitors in dermatomyositis.

RN: How can autoantibody profiles predict myositis phenotype and its disease course?

JP: It’s easier to look at these autoantibody associations by looking at those subgroups that I highlighted in my first talk. I went into the classic autoantibody associations we see in dermatomyositis and some of those updates regarding those phenotypic associations. First and foremost, one of the key pearls is that autoantibodies are helpful in diagnosis and prognosis. There are studies to show that these autoantibodies may even better predict someone's phenotype than a muscle biopsy. And so that's the reason why we order them. But specifically, in looking at dermatomyositis, I talked about some of the phenotypes. For example, anti-melanoma differentiation-associated gene 5 (MDA5) is associated with these “kissing papules” on the hands. The beauty of dermatomyositis is that I can tell the patient exactly what they have just by looking for these kissing papules or ulcers on the hands. And they also tend to have more rapidly progressive interstitial lung disease.

There’s also so much data and literature showing that link of cancer and transcription intermediary factor 1-gamma (TIF1-γ), which is a specific autoantibody associated with the dermatomyositis in the US cohorts, as well as in Asia and Europe. I made it a point that TIF1-γ is one of the most common autoantibodies. Not everyone who has TIF1-γ is going to have a cancer. But as a provider, you’re thinking about it in the context of someone not responding, like in refractory dermatomyositis. You really want to take a step back and analyze if they are not responding because they don’t have enough treatment or if there is a proven cancer, a cell malignancy, that's driving the disease process.

RN: Is there anything else that you'd like our audience know before we wrap up?

JP: One thing I did a highlight a lot throughout is that it's important that rheumatologists, or any providers treating myositis, aggressively treat patients early on so that they do not accumulate damage in their muscles because it's irreversible.