Avacopan controversy: could this vasculitis treatment be withdrawn?
In my previous article we discussed potential new and exciting medications and research that was presented at the recent EULAR meeting in London. This highlighted how rheumatology continues to evolve with new therapies potentially changing patients’ lives.
However, controversy has erupted over a recent therapy that was approved in 2021. You might have seen Avacopan (brand name Tavneos) in the news recently. So what has happened?
What is ANCA Vasculitis, and How Is ANCA Vasculitis Usually Treated?
ANCA vasculitis (Anti-Neutrophil Cytoplasmic Antibody) is a rheumatological condition where the immune system starts attacking the small blood vessels, leading to problems in multiple organs. Originally characterised in the 1980s, it used to carry a poor prognosis with over 80% of untreated people dying within one year of diagnosis. With the introduction of medications like steroids, cyclophosphamide and rituximab, outcomes have improved significantly, with the risk of death in the first year dropping to below 10%.
However, while steroids are very good at controlling inflammation, prolonged high-dose steroid use carries significant risk in itself - including infection, diabetes, high blood pressure and thinning of the bones (to name a few). Therefore, there was a big unmet need for long-term treatment without steroids.
What is Avacopan (Tavneos) and why is it controversial?
Avacopan appeared to be the saviour to meet that unmet need. It blocks an immune system molecule called complement 5a, and is used alongside other treatments to help control ANCA-associated vasculitis whilst reducing the need for long-term steroid treatment.
In 2021, a trial called ADVOCATE was published in the New England Journal of Medicine, a high-profile and well-respected medical journal. It compared Avacopan to the standard treatment of long-term steroids and showed that people on the medication did better at 52 weeks, with fewer disease flare-ups. This was seen as an important breakthrough because it offered the possibility of reducing patients' exposure to long-term steroid treatment.
This led to approval for the use of Avacopan across the world, and it appeared in guidelines as a treatment option in Europe, USA and Britain.
However, a subsequent investigation by the US regulator the FDA revealed that trial data for a small number of patient records had been manipulated, without the knowledge of the doctors conducting the trial. These altered records were the tipping point for the data calculations, resulting in the medication being shown to be superior to steroids. Had this small number of records not been manipulated, the results would not have shown clear evidence that Avacopan performed better than steroids.
The doctors involved then retracted the study from the journal, citing improper research conduct.
Unfortunately, the controversy didn’t end there. Liver side effects in real-world patient populations have been reported at a much higher rate than in the original trial. In Japan, there have been cases of a very rare condition where bile ducts in the liver become damaged and disappear, called Vanishing Bile Duct Syndrome (VBDS). This has led to liver failure, which is very serious.
This has left the future role of Avacopan very tenuous. The FDA has recommended the drug is withdrawn, with similar statements issued by the European Medicines Agency (EMA). In the UK the medication is undergoing a review, but a statement by the Medicines and Healthcare Products Regulatory Agency (MHRA) has suggested extreme caution while this review is taking place. On a personal note, I have stopped this medication on all my patients to be on the safe side.
What does this mean for patients taking Avacopan?
Occurrences like this are extremely rare. Throughout my whole rheumatology career, I have never seen another medication go through such controversy. While it is an intriguing story and has impacted my clinical practice, new innovations in treatment options continue to change my patients lives for the better.
If you are currently taking Avacopan, it is important not to stop treatment without discussing it with your rheumatology team. Although the recent concerns have raised important questions about the medication, treatment decisions should always be made on an individual basis. Fortunately, there remain several effective treatment options for ANCA vasculitis, and ongoing reviews by regulators are designed to ensure medicines remain both safe and effective.
Frequently Asked Questions
Should I stop taking Avacopan (Tavneos)?
No. You should not stop taking Avacopan without first discussing it with your rheumatology team. Stopping treatment suddenly may increase the risk of your vasculitis becoming active again. Decisions about changing treatment should always be made with specialist advice.
I am currently taking Avacopan. Should I be worried?
The recent concerns relate to questions about the original clinical trial data and reports of rare liver complications. However, not every patient taking Avacopan will experience side effects. If you are concerned, speak to your rheumatology team before making any changes to your medication.
What Are the Warning Signs of Liver Problems While Taking Avacopan?
Patients taking Avacopan should seek medical advice if they develop symptoms that could suggest liver problems, including:
- Yellowing of the skin or eyes (jaundice)
- Dark urine
- Pale stools
- Persistent nausea
- Abdominal pain
- Severe itching
- Unusual fatigue
What Treatments Can Be Used Instead of Avacopan?
ANCA vasculitis can still be treated effectively using established therapies including corticosteroids, rituximab and, in some cases, cyclophosphamide. The most appropriate treatment depends on the severity of the disease and each patient's individual circumstances.
Will Avacopan be withdrawn in the UK?
At the time of writing, regulatory reviews are ongoing. Guidance may change as more information becomes available. Patients should discuss any concerns with their rheumatologist rather than making treatment decisions based on media reports.
Does this affect all forms of vasculitis?
No. The concerns discussed in this article relate specifically to ANCA-associated vasculitis and the use of Avacopan in that condition. There are many different forms of vasculitis which are treated in different ways.
Are situations like this common?
No. Drug withdrawals following concerns about clinical trial data are extremely uncommon. Although this has become a high-profile story within rheumatology, the vast majority of new treatments undergo extensive safety monitoring and continue to benefit patients.