BIOTIPRA: BIOmarker-guided Treatment Decisions In Psoriatic and Rheumatoid Arthritis

TNFi drugs remain the most prescribed first-line biologics for patients with rheumatoid arthritis (RA). However, up to 40% of RA patients fail to respond to TNFi treatment. One explanation of non-response is the development of anti-drug antibodies and low drug levels. Studies have consistently shown that: 1. Serum drug levels of monoclonal antibodies (such as adalimumab, certolizumab, infliximab) and the presence of anti-drug antibodies in samples taken at 3 and 6 months correlate with subsequent response at 12 months. 2. Non-responders and those who develop anti-drug antibodies are less likely to receive concomitant methotrexate or, if they do receive it, are on lower doses than responder groups. However, it has not been proven that knowing that a patient had low drug levels or anti-drug antibodies would have improved the outcome; neither has it been shown that introducing or increasing the dose of methotrexate would reduce the formation of anti-drug antibodies, thereby improving outcome. Observational data has revealed that RA non-responders, who exhibit adequate serum drug levels and no detectable anti-drug antibodies, have lower probability of response to another agent with the same mechanism of action (MOA), and may benefit in switching to a drug with a different MOA (12). RA non-responders, who have low detectable serum trough levels and detectable anti-drug antibodies, may benefit in switching to a less immunogenic drug (13, 14). These patients may have a predisposition of developing immunogenicity against the introduced foreign protein (12). Neutralising anti-drug antibodies against the TNFi etanercept or the T-cell co-stimulation inhibitor abatacept have not been detected (10, 12, 15). Furthermore whilst the use and dose of methotrexate at initiation of TNFi, has been associated with lower levels of anti-drug antibodies in our work and others (10, 16), it is not known if increasing the MTX dose once immunogenicity has developed reduces anti-drug antibod