We have helped to fund the largest study ever to look at why anti-TNF drugs, infliximab and adalimumab do not always work for some patients.
Known as the Personalised anti-TNF therapy in Crohn’s Disease study (PANTS) study, the researchers, led by Tariq Ahmad from the University of Exeter, followed 1610 patients with Crohn’s who were starting anti-TNF treatment at 120 UK hospitals.
Infliximab and Adalimumab are used to treat patients with moderate to severe Crohn’s and Colitis when other treatments have not worked. Also known as biological medicines, these drugs work by blocking TNF, a protein which leads to gut inflammation.
Although anti-TNF drugs have given new hope for people with Crohn’s and Colitis, and provided an important treatment option, they do not work in some patients.
The research looked at the reasons why this might be the case in people with Crohn’s Disease. The PANTS study showed that about a quarter of people had no response to the drugs and in one third of people who had responded well initially, the drug stopped working within the first year of treatment.
Nearly 10% of people experienced harmful side effects that resulted in the treatment being stopped. Overall 37% of patients starting anti-TNF drugs were well and still on treatment at the end of the first year.
Anti-TNF drugs are large, complex molecules and in some cases repeatedly taking the drug causes the immune system to recognise it as a potential threat rather than a medicine. This leads to the production of antibodies. These anti-drug antibodies block the action of anti-TNF drugs and increase the rate at which the drugs are removed from the body, which can reduce the effectiveness of treatment.
The researchers from the PANTS study found that the risk of forming antibodies to anti-TNF treatment might be reduced by using personalised dosing particularly at the start of treatment, also prescribing people a thiopurine or methotrexate drug in combination with infliximab and adalimumab.
Anti-TNF drugs have been life-changing for many patients with Crohn’s, but we need to understand why this treatment doesn’t always work. Sometimes patients can go on a long journey to find the best medication for them, but this study means that personalised treatment could be implemented earlier.
Personalised dosing means that the amount of medication given to someone with Crohn’s or Colitis is tailored to them.
The PANTs study also looked at the biosimilar version of infliximab, which was shown to be as safe and effective as the original version, called Remicade. It is not possible to make an exact copy of an originator biological medicine, because they are made from living cells so there will always be some natural and slight differences between them. Therefore, the new versions are known as biosimilars.
The results from the PANTS study suggest there are opportunities to optimise the use of anti-TNF therapies to increase treatment effectiveness. In particular, our data suggests that early personalised dosing, guided by blood level monitoring, together with the use of thiopurine or methotrexate therapy, may help achieve optimal drug levels and minimise the risk of anti-drug antibody formation. We now have cheaper versions of infliximab and adalimumab which means that personalised dose intensification is now more affordable.
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