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The development of anti-TNF therapy

Three reseachers in a lab

The introduction of a new class of treatments for inflammatory arthritis, known as biological therapies, in the early 2000s revolutionised the treatment of this condition. The first of these were treatments targeting a molecule called TNF, which occurs naturally in the body and plays a key role in inflammation. This groundbreaking research is one of our key achievements to date.

Uncovering the importance of anti-TNF

Professors Sir Marc Feldmann and Sir Ravinder (Tiny) Maini, together with their teams at the Kennedy Institute of Rheumatology, have dedicated their lives to studying the causes of rheumatoid arthritis.

In this quest they uncovered a key molecule that causes inflammation and joint damage – known as tumour necrosis factor or TNF.

Initial studies led by Professor Fionula Brennan identified TNF as a key therapeutic target. At the time, it wasn’t widely accepted that blocking a single molecule could stop rheumatoid arthritis.

But in February 1994, Tiny and Marc held a press call to announce the success of the first clinical trial of anti-TNF therapy, which involved just 20 patients.

They showed a now legendary video of a patient, formerly severely disabled due to rheumatoid arthritis, walking unaided up a flight of stairs.

The announcement caught the attention of the national media, and the Kennedy Institute received more than 4,000 calls from people desperate to get hold of this new therapy.

We were key funders of this work through grants to Professors Feldman, Maini and Brennan.

Using anti-TNF in combination with other treatments

Subsequent studies in mice, led by Dr Richard Williams, showed that use of anti-TNF in combination with a treatment targeting T-cells improved treatment response. Large clinical trials demonstrated that combining an anti-TNF blocker called infliximab with methotrexate significantly improved disease symptoms. It also reduced joint damage, which had previously been thought to be progressive and irreversible. 

This pioneering work has had a massive impact. Drugs such as infliximab have transformed the treatment of rheumatoid arthritis and improved the quality of life for many patients.

Changing the guidelines

Anti-TNF treatment is recommended by the National Institute for Health and Care Excellence (NICE) for people with moderate to severe rheumatoid arthritis who:

  • haven’t responded to disease-modifying anti-rheumatic drugs (DMARDs) including methotrexate.
  • have severe, active and progressive disease but haven’t previously been treated with DMARDs.

Under certain conditions it’s also approved for people with psoriatic arthritis and juvenile idiopathic arthritis.

Globally, infliximab (brand name Remicade) has been used to treat more than 1.9 million patients with inflammatory disease since its approval in 1998, which also includes conditions such as Crohn’s disease and ulcerative colitis.

In 2014, three of the four top-selling drugs globally were anti-TNF treatments, with combined worldwide sales of $32.3 billion.

The success of anti-TNF therapy has led to the development of a broader therapeutic field of drugs called biological therapies, which target or mimic the action of biological molecules, including anakinra and tocilizumab.

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