How is the immune system actually supposed to work?

Posted on by Grayson

Our immune systems are amazing. Even when they go wrong, they’re still fascinating — at least to me.

For those of us who aren’t in healthcare or medicine, it’s not always easy to understand and separate out all the cells, the roles they play, etc. Even people who didn’t focus their studies on immunology can be stymied by it, too!

So, how does the immune system work? For the answer, take a look at this video from Kurzgesagt.

Kurzgesagt is one of my favorite YouTube channels, working to make it easier to understand big ideas from health and immunity to our climate crisis and beyond. It’s about making learning fun, regardless of the topic — and that’s absolutely my jam!!

If you want to learn more, check out their recent book — Immune: A Journey Into the Mysterious System That Keeps You Alive. It’s a gorgeous book, full of the same type of art you see in the video.

Note: the Bookshop link in this post is an affiliate link. If you purchase the book from Bookshop, I receive a small kickback at no additional cost to you. If you like that idea, you can check out more of my favorite books here.

Fibromyalgia Patients may benefit from Tocilizumab (Actemra)

Fibromyalgia Patients may benefit from Tocilizumab (Actemra)

Posted on by Grayson

That what an article published August 10, 2023, on HCP Live says.

Now, it’s important to note that fibromyalgia isn’t well understood. That can make it hard to treat because we don’t know what treatments get to the heart of the disease. Actemra is an interleukin-6 inhibitor, often used for Still’s Disease and some other rheumatologic conditions. But, as the article says:

Investigators reported a case series of patients with fibromyalgia receiving tocilizumab treatment. Symptoms were assessed using the revised Fibromyalgia Impact Questionnaire (FIQ), which evaluated pain levels, and the 2016 criteria of the American College of Rheumatology (ACR). Symptoms were compared using the Wilcoxon signed-rank test and neutrophiles from patients with fibromyalgia and matched controls were isolated for transcriptome analysis. Each patient underwent a 40-joint sonography at baseline, including the elbows, wrists, knees, ankles, metacarpophalangeal joints, and thumb interphalangeal joints.

The FIQ and general fibromyalgia symptoms improved at both 4 and 12 weeks with 4 (67%) patients achieving a pain reduction of ≥30% at the 4-week mark and 3 (50%) achieving the same pain reduction at the 12-week mark. No significant changes in joint inflammation, as assessed by the 40-joint sonography, was observed.

There were possible differentially expressed genes identified in primary patients when compared with controls after treatment with tocilizumab. Additionally, 2 genes upregulated in patients with fibromyalgia (C3ARI and PI3) when compared with matched health controls.

The full journal article is available open access, too, in case you’re interested. In it, the authors point out:

We presented a total of two primary and four secondary FM patients who had received subcutaneous tocilizumab for a minimum of 12 weeks. All patients had severe symptoms despite standard treatments. Patients’ FIQR and fibromyalgianess both dropped at 4 and 12 weeks. Four (67%) of them reached a pain reduction of ≥30% at 4 weeks, and three (50%) reached a pain reduction of ≥30% at 12 weeks. Possible differentially expressed genes were identified in primary FM patients when compared with controls and after tocilizumab treatment. Conclusions: FM patients likely benefited from subcutaneous tocilizumab therapy. A randomized controlled trial is needed to verify its efficacy.

Obviously, 6 participants is a super low number. This is something that will require more research, for both those with primary or secondary fibromyalgia. It’s also going to be important to study younger people than 36, the youngest person in this study. Aside from that individual, the next youngest person was 43.

One incredibly interesting thing they noted:

Tocilizumab has been approved to treat cytokine storms in COVID-19 patients []. It could be interesting to investigate how FM symptoms change in patients treated with tocilizumab due to COVID-19.

I agree that this would be an interesting idea — especially because we know from another recent post that MAS is the king of cytokine storms.

Do you have fibromyalgia? If so, would you be willing to try a biologic to see if it helped your symptoms?

ACR Launches New Toolkit Aimed at Measuring RA Outcomes

Posted on by Grayson

The following is a press release issued by the ACR today August 9, 2023:

The American College of Rheumatology (ACR) is excited to announce the launch of its brand-new Rheumatoid Arthritis (RA) Measures Toolkit. In recent years, the landscape of RA care has witnessed remarkable progress, greatly improving outcomes for patients living with this chronic condition. The key to this success: vigilant monitoring of disease activity and functional status, which has enabled rheumatologists to tailor therapies and optimize treatment outcomes. The new RA Measures Toolkit will help rheumatologists and their practices harness the power of standardized RA outcome measures.

“There are currently no national resources available for rheumatologists that guide the effective implementation, collection, and use of disease activity and functional status outcomes for people with RA,” said Jinoos Yazdany, MD, MPH, Professor of Medicine and Chief of Rheumatology at San Francisco General Hospital, University of California, San Francisco and one of the lead authors of the RA Measures Toolkit. “We wanted to develop a tool that allows our community to share best practices and innovations in collecting RA outcomes.”

The toolkit includes a wealth of resources like training guides for nurses and medical assistants who are administering RA outcome surveys (e.g., RAPID-3, PROMIS-PF or patient global assessments), copies of the ACR recommended RA outcome measures (including versions in Spanish and Chinese), sample workflows that rheumatologists are using in different electronic health record systems, and videos featuring best practices from rheumatologists with highly effective strategies for collecting RA measures.

The toolkit also includes guidance on utilizing the ACR’s RISE registry, a powerful tool for tracking performance on the collection of RA measures. With RISE, rheumatologists can effectively monitor and evaluate the implementation of RA measures in their practice and track performance in the Quality Payment Program (QPP).

The new toolkit is not just an asset when it comes to providing rheumatologists with standardized outcome measures for assessing disease activity and functional status for people with RA, it’s also helpful for training medical staff on collecting RA outcome measures.

“Collecting RA outcome measures accurately and efficiently requires a team-based approach that includes nursing staff. Proper training of staff ensures that surveys are administered accurately and consistently, leading to reliable data collection,” said Yazdany. “Moreover, training can help staff engage patients, emphasizing the importance of collecting this information. By providing training materials for staff, the toolkit saves time and allows rheumatologists to focus on taking care of patients.”

The authors of the toolkit interviewed dozens of rheumatologists and their staff to gather best practices and innovations for collecting RA outcomes.

“The information gathered in the toolkit allows our community to learn from both the successes and challenges encountered by our colleagues. The toolkit includes examples of successful clinic workflows, tips for efficient RA outcome measure collection, as well as interviews with high-performing practices,” said Dr. Yazdany.

The RA Measures toolkit e-book can be viewed in full online at https://ratoolkit.kotobee.com/#/.

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

ACR Significantly Concerned with MedPAC’s Latest Recommendations to Cut Part B Drug Reimbursement

Posted on by Grayson

The following is a press release from ACR dated June 15, 2023:

The American College of Rheumatology (ACR) today expressed disappointment that the Medicare Payment Advisory Commission (MedPAC) has recommended yet another cut to physician reimbursement for infusing life-altering treatments as part of its June 2023 Report to the Congress: Medicare and the Health Care Delivery System.

In a letter to MedPAC, ACR took issue with the organization’s recommendation to Congress to keep a six percent add-on payment for the lowest-cost drugs, reduce the add-on payment for mid-to-high-level drugs, and add a payment cap for the costliest drugs.

“While we support efforts to rein in the cost of prescription drugs, we firmly believe that this policy would jeopardize provider practices and patients’ health by reducing access to life-changing provider-administered therapies,” said Douglas White, MD, PhD, president of the ACR. “We urge Congress to address the high cost of drugs at the root cause, like the opaque pharmacy benefit manager business practices, and not at the expense of providers.”

In its recommendation, MedPAC asserted that providers prescribe and administer the highest-price medications in order to receive higher reimbursement. ACR firmly rejects this premise. Administering Medicare Part B drugs in provider offices requires rheumatologists to buy the drug in bulk, maintain full-time staff to administer the treatment, and only bill Medicare after it has been given to the patient.

The six percent of the average sales price (ASP) add-on does not incentivize high-cost treatments, but rather offsets the costs of acquiring, storing, and administering treatments. As written, MedPAC’s recommendation would force providers to cut back on offering cutting-edge therapies or offer these medications at a loss, severely limiting patients’ access to medication and threatening practice viability.

“As providers, it is our job to prescribe the most appropriate treatment for our patients. The add-on payments are not considered in our clinical decision-making. We are concerned that policymakers are concentrating on these add-on payments rather than focusing on policies that address the true cause of drug prices,” said Christina Downey, MD, chair of ACR’s Government Affairs Committee. “The ACR will always express concern when provider payments to administer drugs are eschewed by widely supported policies. Hopefully, the bipartisan movement to reform the PBMs industry will yield meaningful change, and patients will see the benefits.”

EULAR: Systemic JIA, adult-onset Still’s disease ‘are the same disease’

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The following are excerpts of an article released by Healio Rheumatology on June 12, 2023.

Systemic juvenile idiopathic arthritis and adult-onset Still’s disease have been combined into one entity called Still’s disease in new recommendations document presented at the EULAR 2023 Congress.

“The first [overarching principle] was that systemic JIA and adult-onset Still’s disease are the same disease and should be called by the same name, and that is Still’s disease,” [Bruno] Fautrel said.

Read more.

disabled and pregnant? research opportunity

Are you disabled / chronically ill and pregnant?

Posted on by Grayson

The follow is a call for research participants to test a tool. I’m not involved, but it popped up on my radar, but I’m sharing here.

Brandeis University, the Cincinnati Children’s Hospital Medical Center, and others have worked together to develop a new tool – an Accessible Pregnancy Action Plan. This tool would help pregnant people with disabilities think about what they need during pregnancy, during birth, and after having their baby.

They are looking for people between 12 and 36 weeks along in their pregnancies who have disabilities / chronic illnesses and also use English or American Sign Language (ASL) to communicate.

Participants will work on their Action Plan with a peer facilitator, who is also a parent with a disability. These meetings will take place over Zoom. There will be between 2 and 4 meetings.

Most participants will complete the intervention in two sessions. They will be paid $50 per session. Participants who complete the program will also be compensated an additional $50.

Learn more about the study and take the screener here.

screener poster (has all the same information as in the Brandeis link)

Tocilizumab-induced Hypofibrinogenemia in SJIA Patients

Posted on by Grayson

Tocilizumab (or Actemra) is an IL-6 inhibitor commonly used to treat SJIA and other types of autoimmune and autoinflammatory arthritis. As with all medications, we know that tocilizumab has a variety of side effects. These include lowering blood cell counts, making it easier to catch upper respiratory infections, and allergic reactions (in extreme cases).

Before we dig into the latest study on tocilizumab and hypofibrinogenemia, what in the world is hypofibrinogenemia?

Fibrinogen is a protein that is created in the liver. The body uses this, along with other proteins, to form blood clots and stop bleeding. Depending on how often you’ve run into issues with this protein, you may also know it as Coagulation Factor 1. Blood tests like Factor 1 and serum fibrinogen help monitor the level of fibrinogen in the body, either taking a look at how well the protein is working or what level of the protein is in your blood. Medscape has a really deep dive for those interested.

Generally speaking, hypofibrinogenemia is a rare, inherited blood disorder. They’ve found some responsible chromosomes for this. What hypofibrinogenemia does is present as an abnormality in the quality of fibrinogen, and so it causes issues with blood clotting. Folks with this condition might have things like GI bleeding, excess bleeding following surgeries or procedures, or even events like miscarriages. This can often present as bloody noses that take a long time or are difficult to stop. People may require plasma infusions all the way up to a liver transplant, depending on the severity of this condition. They also have to avoid medications such as NSAIDs that tend to alter bleeding and platelets.

Now, what does this have to do with tocilizumab?

According to a study in Nature, tocilizumab can cause hypofibrinogenemia in SJIA patients. They found that 76.47% of SJIA patients receiving tocilizumab had hypofibrinogenemia. The patients with this condition had a variety of disease activity, including inactive disease, and some were on both methotrexate and prednisone as well. However, those medications were determined to have negligible effects on developing hypofibrinogenemia.

It’s important to note that there was a pretty small number of patients retroactively studied. Around 60% of these patients had no specific symptoms, but some symptoms included bleeding gums and increased bruising. Only one patient studied struggled with nose bleeds.

Why is this happening?

IL-1, IL-6, and TNF all affect fibrinogen. IL-1 and TNF negatively affect it, meaning those of us on IL-1 or TNF inhibitors may receive a boost in our fibrinogen levels due to lower IL-1 and TNF levels. Makes sense, right? Well, IL-6 positively affects fibrinogen. That means IL-6 inhibitors like tocilizumab may cause issues such as hypofibrinogenemia.

Should I be worried?

Worried? No. Proactive? Yes.

First, some notes:

They did test these patients and found they did not have the chromosomes related to hypofibrinogenemia. That means this may not have been an inherited condition for them OR there may be a link between SJIA and this condition that we’re unaware of at the moment.

The researchers admit that this retroactive study with a small number of patients means not enough overall data was collected, so a lot more research needs to be done. They also wondered if there’s a difference for adults versus children when it comes to this, especially since hypofibrinogenemia set in after 1-4 doses of tocilizumab in pediatric patients.

Now, as far as being proactive:

If you or your child is on tocilizumab, it’s worth keeping track of symptoms that may be related – nose bleeds, increased bruising, etc. These could be explained by anemia, which needs to be treated, too. However, it’s worth sharing this study with your rheumatologist to see if they can test your fibrinogen levels if/when they test for anemia as well.

You can read the full study here.

A hand is over a blanket while the person the hand belongs to is under the blanket

JIA Patients More At-Risk for Psychiatric and Sleep Conditions

Posted on by Grayson

The following are excerpts from an article on Rheumatology Advisor from June 2, 2023:

Incidence and burden of psychiatric disorders are increased among patients with juvenile idiopathic arthritis (JIA), which may be related to environmental stressors and genetic susceptibility, according to study findings published in ACR Open Rheumatology.

The most common conditions were sleep disorders, mood disorders (such as depression), anxiety disorders, and suicidal ideation. I don’t see sleep disorders as psychiatric in nature, but they’re often classified as such. It’s really silly when we think about it. No amount of therapy will help anyone stop their brain from interpreting chronic pain as a reason to wake up from REM. (That is called alpha-wave intrusion, by the way, and is incredibly common for chronic pain sufferers.)

Researchers concluded, “[P]atients with JIA are at increased risk of developing psychiatric disorders, resulting in an increased burden of psychiatric comorbidities, both in childhood and when reaching adulthood.”

You can read the Rheumatology Advisor article in full here as well as check out the full journal article from Bénédicte Delcoigne, AnnaCarin Horne, Johan Reutfors, and Johan Askling.