Manchester study finds no evidence to suggest that genetic variant helps to predict how rheumatoid arthritis patients will respond to treatment

Researchers in Manchester have found no evidence to suggest that a genetic variant in the DNA of patients with rheumatoid arthritis (RA) helps to predict their response to treatment before they receive it.

The findings of scientists at the NIHR Manchester Musculoskeletal Biomedical Research Unit (BRU) have recently been published in The Pharmacogenomics Journal, following several previous European studies.

Biological therapies were first introduced in the treatment of RA in the late 1990s. Such drugs compared to those traditionally used, target specific components of the immune system and have proven highly effective in the majority of patients receiving them. However, adequate disease control is not achieved in up to 40% of patients.

Researchers cannot currently predict who is going to respond well to any given treatment and so such drugs are prescribed on a trial and error basis. In line with the BRU’s vision of Treating arthritis: right first time, scientists set out to identify factors which can predict response to treatment before it is administered.

By comparing parts of the DNA sequence between different patients, researchers can see different compounds at the same position; this variation at a specific position is called a single nucleotide polymorphism or SNP.

Whilst the majority of these SNPs seem to cause no observable differences between individuals, some can influence a number of characteristics including eye colour, susceptibility to certain diseases or even in how patients respond to drugs. An SNP located within a certain region of DNA called PDE3A-SLCO1C1 has been linked with response to the group of biologic drugs known as anti-TNF inhibitors in two previous studies.

The Manchester study, led by Samantha Smith, Research Associate, The University of Manchester Institute of Inflammation and Repair, set out with the aim of replicating this finding in a large UK population of RA patients receiving anti-TNF therapies.

DNA samples from more than 1,500 patients in the Biologics in Rheumatoid Arthritis Genetics and Genomics Study Syndicate (BRAGGSS) were analysed. BRAGGSS is a study which recruits RA patients across the UK who are about to commence or currently receive treatment with biologic drugs, and has the specific aim of identifying factors able to predict response to treatment.

As a part of the study, measurements of a patient’s disease activity were taken prior to treatment and following three, six and twelve months on treatment, to determine their response. Patients also provided a blood sample so that DNA could be extracted for analysis.

Researchers examined the DNA to determine whether the previously reported SNP at the PDE3A-SLCO1C1 gene region differed between patients who responded well to treatment with anti-TNF biologics and those who did not respond.

Anne Barton, Professor of Rheumatology and BRU Inflammatory Arthritis in Adults Theme Lead, said: “It is important that any factors reported to be predictive of treatment response are replicated in large independent populations to ensure that the associations are real, as they could go on to be used in clinics to help patients and doctors to choose the right treatment.

“Through this research we found no evidence to support the use of this SNP in predicting response to treatment with anti-TNF biological therapies in a UK population. It could be that this SNP is only predictive in certain populations, as the previously reported association was found in Dutch and Spanish rheumatoid arthritis patients and so further experiments in these populations, and others, are needed to investigate this further.”