Exploring New Ways to Keep ANCA Vasculitis in Check

February 12, 2024

ANCA Vasculitis is a rare but serious condition where the body’s immune system mistakenly attacks its own blood vessels, causing inflammation. This falls into a group of illnesses known as autoimmune diseases. Each year, about 3 out of every 100,000 people get diagnosed with it, mainly those who are between 50 and 70 years old. One of the biggest hurdles in treating ANCA Vasculitis is preventing it from coming back, which calls for some creative solutions to keep the disease in remission.

A groundbreaking study titled “Maintenance of Remission of ANCA Vasculitis by Rituximab Based on B Cell Repopulation Versus Serological Flare: A Randomised Trial” sheds light on a novel tactic for tackling this challenge. It zeroes in on the drug Rituximab, which helps calm the immune system’s overreaction that’s at the heart of this condition.

Why Focus on Rituximab for ANCA vasculitis?

Rituximab targets B cells, which play a big part in the body’s overactive immune response seen in ANCA Vasculitis. Doctors usually give this medication when they notice B cells coming back after treatment or when there’s a spike in ANCA levels, which can mean the disease is flaring up.

The Two Approaches Explained

The study looks at two ways of deciding when to give extra doses of Rituximab:

The first way is based on whether B cells are starting to show up again after being knocked down by treatment.
The second way relies on monitoring ANCA levels in the blood, even if the patient isn’t showing any symptoms, to catch any potential flare-ups.

What the Study Found

This research offers new insights by comparing these two strategies. It found that using Rituximab based on the return of B cells leads to fewer relapses than waiting for ANCA levels to rise, over an average follow-up of 4.1 years. This result supports the idea that tailoring treatment to each patient’s specific situation can really make a difference in managing complex autoimmune diseases like ANCA Vasculitis.

However, both methods have their challenges, such as predicting disease flares accurately and the feasibility of frequent testing. The study also closely monitored safety, noting similar side effects in both groups but a slightly higher risk of serious issues related to COVID-19 in those treated based on B cell repopulation.

Personalized Care for ANCA Vasculitis is Key

The findings highlight that there’s no one-size-fits-all answer to treating ANCA Vasculitis. Some patients might do better with one approach over the other, emphasizing the importance of customizing treatment plans.

Looking Ahead

This study is a significant step forward in improving how we maintain remission in ANCA Vasculitis. It encourages us to keep asking questions and searching for better ways to care for those affected by this disease.

Even though the medical terms might sound complex, they’re part of understanding how to best manage ANCA Vasculitis. As we work to unravel these complexities, it’s crucial to keep learning, adapting, and showing compassion for those living with this condition.

This research marks an important progress in our journey, and we’re committed to sharing the latest and most accurate information to help make informed health decisions. Our dedication to understanding and empathizing with your health challenges stands firm.

References

Zonozi R, Cortazar FB, Jeyabalan A, Sauvage G, Nithagon P, Huizenga NR, Rosenthal JM, Sipilief A, Cosgrove K, Laliberte KA, Rhee EP, Pendergraft WF 3rd, Niles JL. Maintenance of remission of ANCA vasculitis by rituximab based on B cell repopulation versus serological flare: a randomised trial. Ann Rheum Dis. 2023 Dec 11:ard-2023-224489. doi: 10.1136/ard-2023-224489. Epub ahead of print. PMID: 38123922.

Medical Disclaimer

The information in this video is not intended nor implied to be a substitute for professional medical advice, diagnosis or treatment. All content, including text, graphics, images, and information, contained in this article is for general information purposes only and does not replace a consultation with your own doctor/health professional

Diseases and Conditions Self-Injection Videos

How to inject Actemra and Kevzara

October 24, 2017

In this week’s edition of RheumDoctor, Dr. Farrell will teach how to inject Actemra and Kevzara in the comfort of your home. Both of these medications work by blocking interleukin-6, a cytokine involved in inflammation. Kevzara, also known as sarilumab, recently obtained FDA approval for the treatment of rheumatoid arthritis. Actemra, also known as tocilizumab, is also prescribed for rheumatoid arthritis but also recently obtained FDA approval for the treatment of giant cell arteritis. Without further adieu…

Preparing for your injection

Keep your medication stored in the refrigerator until use
- Before injecting medication, take the prefilled syringe out of the refrigerator.
- Allow it to warm up to room temperature.
Pick a place in your house that is clean and has room for your materials (such as the kitchen table).
Wash your hands thoroughly with either:
- Soap & water
- Hand sanitizer
Chose an area to inject – Thigh or Stomach.
- Chose an area that is intact and clear.
- It should not have any of the following:
  - Cuts
  - Scrapes
  - Bruises
  - Psoriasis patches
  - If you have extensive psoriasis, inject between patches
  - Moles
  - Scars
- Please rotate area each time you inject (shown in picture below).

Cleanse chosen area
- Cleanse chosen area with either of the following:
  - Alcohol swab
  - Alcohol and a cotton ball
- Use the chosen alcohol material to “swipe” area
  - Can either use a circular motion or wipe in “strips”
  - Allow the area to dry

Injecting Actemra or Kevzara with a prefilled syringe

Pull off the cap and observe the syringe.
Pinch the skin around the injection site and enter at a 45-degree angle
Press the plunger (slowly) to administer the medication
Once the medication is fully administered, the plunger will reach the bottom and a spring will place a cover over the needle

After the injection

Properly dispose of the entire prefilled syringe
- Sharps Container
  - Can be purchased at your local pharmacy
  - Disposal
- - - Hospitals may take full sharps containers, ask first.
    - Pharmacies and Doctors’ offices are not allowed to take used syringes or needles
Discard remaining materials in the trash (cap, alcohol swabs, etc.)

For more information about Actemra.

For more information about Kevzara.

Credits

Jessica Farrell, PharmD. Clinical Pharmacist, The Center for Rheumatology/Associate Professor, Albany College of Pharmacy and Health Sciences

With the help of Autumn Koniowka. Doctor of Pharmacy Candidate Class of 2018, Albany College of Pharmacy and Health Sciences, and Megan Phillips. Doctor of Pharmacy Candidate Class of 2018, Albany College of Pharmacy and Health Sciences.

A special thanks to Tammy Garren, PhD. Instructional Designer, Center for Innovative Learning, Albany College of Pharmacy and Health Sciences.

Injection site image: By British Columbia Institute of Technology (BCIT). Download this book for free at http://open.bccampus.ca [CC BY 4.0 (http://creativecommons.org/licenses/by/4.0)], via Wikimedia Commons

Medical Disclaimer

This information is offered to educate the general public. The information posted on this website does not replace professional medical advice, but for general information purposes only. There is no Doctor – Patient relationship established. We strongly advised you to speak with your medical professional if you have questions concerning your symptoms, diagnosis and treatment.

Diseases and Conditions

Tocilizumab: the new wonder drug for giant cell arteritis

June 7, 2017

People aged 50 years and above can develop giant cell arteritis

On May 22nd 2017 the FDA approved weekly subcutaneous tocilizumab (trade name Actemra®) to treat giant cell arteritis, a type of vasculitis that can cause blindness and in some cases death. Why is this so important and how does this change everything? The answer is simple. Previously there were no effective treatments. Rheumatologists used steroids like prednisone at high doses for months on end. Many people would get lot’s of side effects due to the steroids and even this did not guarantee success. Typically it takes many years for a medication to get FDA approval. Although it did take more than a year to get approval, the process in this particular situation was fast-tracked. Before I get into how we got to where we are today, let’s start with some background.

What is giant cell arteritis?

Giant cell arteritis is a type of large vessel vasculitis that tends to affect people aged 50 years and above.

Pay attention to the spelling, a-r-T-E-r-i-t-i-s. This is completely different from a-r-T-H-r-i-t-i-s.

Giant cell arteritis is an autoimmune disease that inflames blood vessels not joints. More specifically, it inflames the aorta and the branches of the aorta. Sometimes it’s also called temporal arteritis, but that’s not a good name for it because the temporal arteries are one type of artery that giant cell arteritis can affect. We call this autoimmune disease giant cell arteritis because if you biopsy an artery you will find “giant cells” also called “granulomatous inflammation”, when you look at it under a microscope. In fact, this is one way rheumatologists make the diagnosis.

By LadyofHats, Mariana Ruiz Villarreal [Public domain], via Wikimedia Commons

What are the symptoms of giant cell arteritis?

Giant cell arteritis can present in many ways. It really depends on the affected blood vessel(s). If there is vasculitis in a temporal artery, then people tend to have a bad headache and a cramping pain when chewing food. Maybe the blood vessels supplying the ears has vasculitis? This can cause a change in hearing and vertigo. If the blood vessels supplying the eyes is affected, then it can cause blindness. In some cases, people aren’t even aware of it. They get a CT scan for some unrelated issue and the radiologist finds a large aortic aneurysm. Giant cell arteritis is a condition that causes inflammation throughout the body, so many people present with fevers, drenching night sweats, and weight loss.

One of the most common presentations of giant cell arteritis is polymyalgia rheumatica. Sometimes doctors simply call it “PMR”. While 40% of people with giant cell arteritis have polymyalgia rheumatica, 10-20% of people with polymyalgia rheumatic develop giant cell arteritis. Polymyalgia rheumatica is an autoimmune disease that causes muscle pain and stiffness in the shoulders, neck, hips, and thighs. Finally, like giant cell arteritis, it affects people aged 50 years and above.

How do you diagnose giant cell arteritis?

There are many ways to diagnose giant cell arteritis. First of all, blood tests like the CRP and the sed rate are usually very high. These are tests that measure the amount of inflammation in your body. Ideally you want to have a biopsy of the affected blood vessel but sometimes that’s not possible. The biopsy should show giant cells but this only occurs in about 50% of cases so having a negative biopsy does not necessarily completely exclude disease. When a biopsy is not possible, certain imaging studies can help like ultrasound, CT angiography, and PET scans.

How is giant cell arteritis treated?

Steroids, steroids, and more steroids. If a doctor suspects that someone has giant cell arteritis, they immediately start treatment with high doses of steroids. This happens even before the workup! Once the diagnosis is firmly made the steroids are slowly tapered. This happens over months. It’s not uncommon to still be on steroids for YEARS after the diagnosis. In many cases, the vasculitis returns. This can be very frustrating and upsetting. Rheumatologists have tried to treat people with medications like methotrexate in addition to steroids, but these haven’t really worked.

That is until now…

How it began

In 1990 researchers tested the blood of 15 people who had untreated giant cell arteritis. They found high levels of a cytokine called interleukin 6 (IL-6) in their blood. After treatment with steroids, their interleukin 6 levels decreased except for a few people. Which is unsurprising since many people with giant cell arteritis relapse.

At that time, we didn’t have any medications that specifically blocked interleukin 6.

Flash forward to 1997. A company based in Japan called Chugai Pharmaceuticals began research on tocilizumab to treat rheumatoid arthritis. Tocilizumab is biologic humanized monoclonal antibody that blocks interleukin 6. Then in 2003 Genentech co-developed the medication. Genentech’s tocilizumab is called Actemra®. Finally in 2010 the FDA approved Actemra® for to treat moderate to severe rheumatoid arthritis.

Giant cell arteritis and tocilizumab

Now remember how researchers found high levels of interleukin 6 in the blood of people with giant cell arteritis? What would happen if you treated someone who has giant cell arteritis with tocilizumab? Would they go into remission? Maybe you could taper off steroids more quickly? That’s exactly what some Swiss scientists showed in 2011. They treated 5 people with giant cell arteritis with tocilizumab. All of them went into remission and all of them were able to taper off the steroids quickly. The elevation and blockade of interleukin 6 appeared to be especially relevant for the treatment of giant cell arteritis. But this was a case series with a very short follow-up time. Was this a fluke or were they onto something?

In 2012, researchers started a larger phase 2 study. This time they studied 30 people and they randomized them to either receive tocilizumab+prednisone or placebo+prednisone. The results were favorable:

85% of the people who received tocilizumab and 40% of the people who received placebo went into remission by week 12.
15 % of the people who received tocilizumab relapsed, where 80% of the people who received placebo relapsed by week 52.
People who received tocilizumab on average stopped prednisone 12 weeks in advance compared to people who received placebo.
35% of people who received tocilizumab had a serious side effect, where 50% of people who received placebo had a serious side effect.

The last act

At last year’s American College of Rheumatology conference, Dr. John Stone presented data from the GiACTA trial, which was a randomized, double-blind, placebo-controlled trial. This was a phase 3 study. So they looked at more people from various locations. There were 251 people placed into 4 different groups.

A short course of prednisone (26 weeks) + a weekly subcutaneous placebo
A long course of prednisone (52 weeks) + a weekly subcutaneous placebo
A short course of prednisone + weekly subcutaneous tocilizumab
A short course of prednisone + every other week subcutaneous tocilizumab

The results

56% of people who received weekly tocilizumab achieved and stayed in remission after 12 months.
53.1% of people who received every other week tocilizumab achieved and stayed in remission after 12 months.
14% of people who received a short course prednisone + placebo were in remission after 12 months (p <0.0001).
17.6% of people who received a long course of prednisone + placebo were in remission after 12 months (p ≤ 0.0002).
People who received tocilizumab received about half as much prednisone overall.
Adverse events were about the same in all groups and there were no deaths or vision loss.

The conclusion

Due to these extraordinary results and the dire need for effective treatment for giant cell arteritis, the FDA approved weekly subcutaneous tocilizumab. I don’t know about you, but I’m very excited about this! Finally a medication that works! Mind you, it doesn’t work in every single case but this is definitely is a step forward. And to add icing on the cake, although tocilizumab doesn’t eliminate the need for steroids, it does drastically decrease the total amount people get…another big plus.

To continue learning more about rheumatology and how to read research articles from their original source, please read on!

References

https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm559791.htm

Rheumatology Secrets, 3rd edition

Dasgupta B, Panayi GS. Interleukin-6 in serum of patients with polymyalgia rheumatica and giant cell arteritis. Br J Rheumatol. 1990 Dec;29(6):456-8.

https://www.drugs.com/history/actemra.html

Seitz M, Reichenbach S, Bonel HM, Adler S, Wermelinger F, Villiger PM. Rapid induction of remission in large vessel vasculitis by IL-6 blockade. A case series.Swiss Med Wkly. 2011 Jan 17;141:w13156. doi: 10.4414/smw.2011.13156.

Villiger PM, Adler S, Kuchen S, Wermelinger F, Dan D, Fiege V, Bütikofer L, Seitz M, Reichenbach. Tocilizumab for induction and maintenance of remission in giant cell arteritis: a phase 2, randomised, double-blind, placebo-controlled trial.Lancet. 2016 May 7;387(10031):1921-7. doi: 10.1016/S0140-6736(16)00560-2. Epub 2016 Mar 4.

Stone JH, Tuckwell K, Dimonaco S, Klearman M, Aringer M, Blockmans D, Brouwer E, Cid MC, Dasgupta B, Rech J, Salvarani C, Spiera RF, Unizony SH, Collinson N. Efficacy and Safety of Tocilizumab in Patients with Giant Cell Arteritis: Primary and Secondary Outcomes from a Phase 3, Randomized, Double-Blind, Placebo-Controlled Trial [abstract]. Arthritis Rheumatol. 2016; 68 (suppl 10). http://acrabstracts.org/abstract/efficacy-and-safety-of-tocilizumab-in-patients-with-giant-cell-arteritis-primary-and-secondary-outcomes-from-a-phase-3-randomized-double-blind-placebo-controlled-trial/. Accessed May 29, 2017.