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Cancer patients being treated with immunotherapy called checkpoint inhibitors often experience arthritis as a side effect. The first clinical trial of its kind in the UK is now open to test whether a powerful arthritis treatment is suitable for patients receiving ongoing cancer treatment.

The REmission induction of Arthritis caused by Cancer ImmunoTherapy (REACT) trial, led by researchers at Queen Elizabeth Hospital Birmingham (QEHB) and the University of Birmingham, is one of the first global studies of its kind.

The trial, which is being delivered through the National Institute for Health and Care Research (NIHR) Birmingham Biomedical Research Centre, hosted by University Hospitals Birmingham, will recruit 70 patients across sites in the UK.

It aims to find out whether initial treatment with anti-TNF (anti-tumour necrosis factor) therapy in cancer patients receiving a type of cancer immunotherapy called an immune checkpoint inhibitor (ICI) can better control this type of arthritis, without significantly interfering with their cancer therapy.

Professor Benjamin Fisher, Consultant Rheumatologist at QEHB and Chief Investigator of the REACT trial, said: "Immune checkpoint inhibitors have revolutionised cancer treatment, but they come with the risk of severe inflammatory side effects, including arthritis.

“The REACT trial aims to provide critical insights into the most effective initial treatments for patients suffering from this debilitating condition, potentially improving their quality of life significantly without affecting their cancer treatment."

Immune checkpoint inhibitors are drugs that block 'off' signals in the immune system to help it fight cancer. While they have revolutionised cancer treatment, they can cause severe inflammatory side effects, including arthritis - which affects at least 5% of treated cancer patients and significantly impacts quality of life. It may persist even after ICI is stopped and may require treatment with drugs to suppress the immune system.

The current treatment approach for arthritis that has resulted from ICI treatment is to typically start with steroid tablets, then gradually try other treatments if these fail. Anti-TNF is currently often the last treatment used. Anti-TNF is a drug that blocks an immune protein called Tumour Necrosis Factor.

TNF inhibitors have good evidence for other types of arthritis but there is no evidence for patients with ICI-induced arthritis to safely guide initial treatment strategy. This trial will therefore be the first to test the effects of immune suppressing drugs on cancer outcomes in response to ICI.

Rebecca Smith, 53, from Solihull, was diagnosed with eye cancer in early 2020, just before the pandemic. Within weeks, she underwent surgery to remove her eye and adapted quickly to life with an artificial eye. For several years, she remained cancer-free - until the disease spread to her liver.

“I started immunotherapy last year, and while it offered hope, the side effects were brutal,” Rebecca explains. “I developed colitis, meningitis, and severe arthritis that attacked 90% of my joints. I couldn’t climb stairs, get dressed, or even get out of bed without help. It was devastating.”

These side effects forced Rebecca to take a year off work. “I love my job, but I simply couldn’t manage. Every cycle of treatment left me in hospital with side effects. It was a vicious circle.”

Standard steroid therapy offered little relief and clashed with her ongoing immunotherapy. That’s when her consultant suggested the REACT trial.

“I jumped at the chance. I thought, if it doesn’t work, at least I’ve tried - and maybe I’ll help others,” she says.

Rebecca was randomly assigned to receive adalimumab injections every two weeks. The impact was life-changing: “It’s been a godsend. My pain has eased, I can walk, I’ve returned to work, I can even wear heels again! My quality of life is back to what it was before.”

She still experiences mild aches before her next dose, but the improvement has been dramatic. “I’ve gone from being housebound to going on holiday and making memories with my family. Trials like this give people hope - and that’s priceless.”

Rebecca shares her journey on Instagram (@one_eye_survivor_living_life) to inspire others: “Don’t lose hope. Cancer and its side effects aren’t the end of the world. If you get the chance to join a trial, take it. It might change your life - it’s certainly changed mine.”

To compare the safety and effectiveness of these treatment strategies, the trial aims to recruit 70 ICI-induced arthritis patients across multiple centres in the UK. Participants will either receive current standard of care (initial steroid treatment in the form of prednisolone) or the anti-TNF drug adalimumab.

Treatments will be gradually reduced once the arthritis is controlled, or further treatment given if needed. The research team will compare the proportion of patients in each treatment group who have no arthritis and no steroid use six months after the start of treatment.

Researchers will also compare how fast the arthritis is controlled, and will continue to follow patients until one year to compare arthritis activity, quality of life, ability to function, total amount of immunosuppressive drugs received over time, number of ICI doses missed, new immune-related side effects, cancer outcomes and survival.

The clinical trial has received funding of more than £1 million from the National Institute for Health and Care Research (NIHR), supported by the NIHR UK Musculoskeletal Translational Research Collaboration and the NIHR/Wellcome Trust Birmingham Clinical Research Facility. The study will run until August 2028.