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Call for anti-TNF Availability for Takayasu's Arteritis from NHS

Manchester — Anti-tumour necrosis factor (TNF) therapy may be an option for patients with Takayasu's arteritis for whom tocilizumab is ineffective or not tolerated, suggest experts referring to new observational data presented at this year's annual conference of the British Society for Rheumatology (BSR). 

Rheumatology registrar, Dr Matthew Colquhoun, from Imperial College Healthcare Trust in London, presented the real-world data from patients attending Hammersmith Hospital, a UK tertiary referral centre.

"Anti-TNF therapy is already an established option worldwide, but not in the UK," he pointed out, adding that, "not only is there a failed trial of tocilizumab, but here we provide further observational evidence [of anti-TNF therapy] that is supportive in a highly previously treated cohort [of Takayasu arteritis patients] with a long duration of treatment persistence."

"We also provide anecdotal evidence of success in previously cyclophosphamide-refractory disease, and we suggest that there may be some patients in whom cyclophosphamide could be avoided altogether," added Dr Colquhoun.

Therapy a 'Rational Choice'

He stressed that anti-TNF therapy was "a rational choice" if the patient has a relevant co-morbidity such as uveitis or inflammatory bowel disease, for example, and in women of childbearing age. 

There are cost indications too, he added. "Unusually for the NHS, they have approved the drug that costs more [tocilizumab], and furthermore, there are biosimilar anti-TNF inhibitors coming onto the market that cost around £500 per year."

Takayasu's arteritis is a rare (0.4 to 2 cases per million/year) large vessel vasculitis affecting the aorta and proximal branches, and is more common in women than men (9:1), affecting those mostly in their 30s and 40s. It is also more common in the Asian population . 

Typically, patients receive corticosteroids and immunosuppressants including methotrexate, after which another disease-modifying antirheumatic drug (DMARD) might be added. and if this fails, then a biologic drug, for example, tocilizumab or anti-TNF therapy.

"For anti-TNF therapy, we have around 20 years of observational evidence [in Takayasu's arteritis] but no randomised controlled trials, while for tocilizumab we have around 20 observational studies and one randomised controlled trial," explained Dr Colquhoun. Around 80-90% of patients show at least a partial clinical response to both anti-TNF and tocilizumab, and angiographic stabilisation or improvement. Comparative observational studies show the two treatments are similar, he noted.  

"This interests us because the NHS has only commissioned tocilizumab for the treatment of Takayasu and not anti-TNF inhibitors, unlike in the United States where the ACR [American College of Rheumatology] 2022 guidelines advise anti-TNF over tocilizumab. France and EULAR see them as equivalent," he said. 

"Given these data and a trial of tocilizumab that essentially failed – why can't we use both drugs?" he suggested, and as such Dr Colquhoun began a set out with a study that described the characteristics and outcomes of Takayasu patients treated with anti-TNF at Hammersmith Hospital, London. 

Study Details

A total of 14 Takayasu’s arteritis patients treated with anti-TNF agents out of a total cohort of 158 patients were retrospectively evaluated. 

Of these 8.8% were treated with anti-TNF therapy, average age at diagnosis was 27 years, 93% were women, and 71% Caucasian, 21% Asian. They had severe disease with 42.8% having another auto-immune co-morbidity that justified treatment with anti-TNF therapy, for example ankylosing spondylitis, uveitis, or Crohn's disease, said Dr Colquhoun. 

In patients treated with anti-TNF therapy, the researchers found a partial disease response in 78.5%, a complete response in none, a clinical response in 76.5%, while 71.1% had stable, radiographic disease, 14.2% were off their conventional synthetic DMARDS, and average treatment duration was 70 months. "In terms of failure of treatment, these occurred at two (early failure) 13, 15, and 93 months (radiographic progression)," reported Dr Colquhoun.

Dr Colquhoun also described some case studies. One was a 47-year-old woman with refractory disease, diagnosed in 1998 who failed cyclophoshamide, azathioprine, methotrexate, and etanercept. Her disease was controlled with infliximab but flared when she discontinued treatment during pregnancy and regained control when restarted treatment. She experienced late progression at 93 months. He also outlined other patients controlled with etanercept, and another who switched from tocilizumab to anti-TNF therapy. 

Notwithstanding the small numbers of retrospective data in his study, and comparing to published data, the researcher remarked that, "we saw slightly worse angiographic stability, compared to other meta-analysis data, and a slightly lower partial treatment response of 70%, compared to 80-90% in published data. But we followed up patients for a long time – 70 months is longer than other studies, which average 37 months."

Next Steps

Delegate, Dr Bridget Griffiths, from the Freeman Hospital, Newcastle-upon-Tyne, commented on the study. Dr Griffiths is the clinical lead for the regional specialised rheumatology service, including over 2000 patients with autoimmune connective tissue diseases and vasculitis. "The data are now available, and the process to follow is to submit a policy proposition so it can be considered by the NHS England. They like evidence – ideally randomised controlled trials but it will accept observational data. They will probably look at some costs, and tocilizumab is probably more expensive than infliximab so I think it's a good opportunity to submit a proposition, and hopefully then it will be officially approved for Takayasu arteritis."

"We used infliximab in the early 2000s before the latest NHS England specialised guidance was in place, and we had more flexibility, despite postcode variation," she pointed out. 

"I think it is more pertinent now that this is being discussed, because previously you could submit a request to use it through NHS England's individual funding request, but now they would say this one patient is one of a cohort so we need to have a policy change. It takes a lot of work but it's needed."

Dr Colquhoun declares honoraria and support to attend a conference from Pfizer. Dr Griffiths was Chair of the Specialised Rheumatology Clinical Reference Group.