Category: macrophage activation syndrome

New MAS Warning Sign Discovered

Posted on by Grayson

A journal article published on December 20, 2023, shows the discovery of a new MAS warning sign.

Intermediate monocytes produce TNF and IL-1B. Medications, such as TNF-inhibitors and IL-1B inhibitors, help suppress the ongoing inflammatory responses these IMs bring.

IMs are also known to increase inflammation within the cardiovascular system. This may be a part of why many rheumatic patients also have cardiovascular disease.

For people with adult-onset Still’s (AOSD) specifically, there was an uptick in the measured IMs leading up to and during MAS events. This could help explain why the IL-1B inhibitor Anakinra is a go-to treatment for MAS.

The study even went on to point out that this could become a biomarker, allowing us to catch MAS events earlier. This would hopefully lead to better outcomes, too.

Read the full article below.

Jia, J., Wang, M., Ma, Y. et al. Neutrophil extracellular trap-induced intermediate monocytes trigger macrophage activation syndrome in adult-onset Still’s disease. BMC Med 21, 507 (2023). https://doi.org/10.1186/s12916-023-03231-9 

Continuous Anakinra IV for a Patient With Macrophage Activation Syndrome

Continuous Anakinra IV for a Patient with MAS

Posted on by Grayson

The following is from a research article published August 4, 2023.

Abstract

Macrophage activation syndrome (MAS) is a type of hemophagocytic lymphohistiocytosis (HLH), which occurs due to excessive stimulation of the immune system. Common precipitants of MAS include disseminated infection or underlying rheumatologic disorders such as adult-onset Still’s disease which is characterized as an inflammatory arthritis with daily fevers and a salmon-colored rash. We present a case of a patient with probable adult-onset Still’s disease and subsequent disseminated cytomegalovirus (CMV) infection, who met the criteria for MAS based on the presence of a fever, cytopenia in multiple cell lines, elevated ferritin, presence of hemophagocytosis on bone marrow, low fibrinogen, and mild splenomegaly on physical exam. The patient responded to treatment with continuous anakinra infusion and ganciclovir for treatment of CMV. Though cytotoxic medications such as etoposide have traditionally been considered first-line treatment for HLH/MAS, interleukin-1 inhibitors such as anakinra are emerging as a less cytotoxic alternative.

Key Quotes

MAS is often considered the most feared consequence of patients with AOSD and has been reported to occur in close to 15% of these patients. Treatment options for MAS currently include IV Igs, corticosteroids, etoposide, cyclosporine, tocilizumab, and anakinra. Though anakinra is generally administered via the subcutaneous route, the IV route may be preferred in critically ill patients due to increased absorption and a decreased risk of bleeding if an underlying coagulopathy is present.

Recent case series and reports have highlighted the role of IV anakinra infusion at doses of 1-2 mg/kg in the treatment of patients with macrophage activation syndrome.

What does this mean?

We have some new-ish options for treating MAS! Now, that isn’t new as in a new drug, but it is a new delivery method for Anakinra (Kineret) specifically.

This is important for a range of reasons, but especially considering that MAS — “the most severe form of cytokine storm” — has occurred in COVID-19 patients. Between happening during infection, we also know that COVID-19 causes major upset to the body’s systems, leading to the development of a host of conditions that may themselves cause MAS. And, in children, MIS-C may often appear — a condition somewhere between MAS and Kawasaki Syndrome.

In the rheumatology world, MAS is most common in AOSD and SJIA, happening in 10-15% and roughly 10% of patients respectively. It can occur in patients with other autoimmune and autoinflammatory arthritis types, most often Systemic Lupus Erythematosus (SLE). According to research, mortality in MAS cases is between 20-53%. It’s hard to know exact numbers when MAS may not be caught before a patient dies — if they even can access healthcare and try to do so.

This is also part of why it is imperative for AOSD, SJIA, and SLE patients to all know the early signs and symptoms of MAS — and to trust your gut if you feel something is really wrong.

Citation

Gullickson M, Nichols L, Scheibe M (August 04, 2023) A Novel Therapy for a Rare Condition: Continuous Anakinra Infusion for a Patient With Macrophage Activation Syndrome. Cureus 15(8): e42968. doi:10.7759/cureus.42968

Emapalumab Induces Remission of MAS

Posted on by Grayson

Amazing news! Emapalumab can help treat Macrophage Activation Syndrome (MAS)!

an illustration of ifny
Source

The brand name for emapalumab is Gamifant. It’s FDA-approved to treat hemophagocytic lymphohistiocytosis (HLH), which is pretty similar to MAS in many respects.

The following paragraph is from a summary on Contemporary Pediatrics:

Emapalumab, a fully human anti-interferon-γ (IFNγ), demonstrated efficacy for inducing remission of macrophage activation syndrome (MAS) secondary to systemic juvenile idiopathic arthritis (sJIA) or adult-onset Still’s disease (AOSD) in patients who failed standard care with high-dose glucocorticoids, with or without anakinra (Kineret; Sobi) and/or cyclosporin, according to a recent study.

This is amazing news. MAS is a terrifying secondary condition. It is most common in SJIA and AOSD, but can pop up in lupus and other conditions. If you want to learn more about MAS itself, I covered a session on the condition at the 2017 ACR annual meeting. You can learn more about the immunology on Frontiers.

Normal treatment involves a ton of gluticosteroids and often Anakinra/Kineret. That doesn’t do it for enough patients, though. It’s important to note that there was a small N (or participant number) of 14. However, by week 8, 13 of the 14 patients had achieved remission. That’s not shabby at all.

Most importantly, no deaths were reported during the trial and the long-term follow-up. That’s amazing for a condition that has a mortality rate between 20-53%.

This was a phase II, open-label, single-arm trial conducted in the US, UK, Spain, Italy, and France. I was also happy to see that Dr. Alexei Grom, who I interviewed several years ago, was a part of this study.

Read more of the summary on Contemporary Pediatrics. Or, you can read the full journal article, Efficacy and safety of emapalumab in macrophage activation syndrome, here.