Psoriatic arthritis: the role of self-reported non-adherence, non-trough drug levels, immunogenicity and conventional synthetic DMARD co-therapy in adalimumab and etanercept response

Objective The aim of this study was to assess the relationship between self-reported non-adherence, non-trough drug levels, immunogenicity and conventional synthetic DMARD (csDMARD) co-therapy in TNF inhibitor (TNF-i) drug response in PsA. Methods Serum samples and adherence questionnaires were collected at baseline, 3, 6 and 12 months for PsA patients prescribed TNF-i. Non-trough adalimumab (ADL) and etanercept (ETN) drug levels were measured at 3 and 6 months using commercially available ELISAs. Clinical response was assessed using PsA response criteria (PsARC) and change in 28-joint DAS (Delta DAS28) between baseline and 3, 6 and 12 months. Results In 244 PsA patients (52.5% ADL and 47.5% ETN), self-reported non-adherence was associated with PsARC non-response over 12 months using generalized estimating equation (GEE) modelling (P = 0.037). However, there was no significant difference between non-trough ADL or ETN drug levels based on self-reported non-adherence. Higher ETN levels at 3 months were associated with PsARC response at 3 (P = 0.015), 6 (P = 0.037) and 12 months (P = 0.015) and over 12 months using GEE modelling (P = 0.026). Increased ADL drug levels at 3 months were associated with greater Delta DAS28 at 3 months (P = 0.019). ADL anti-drug antibody-positive status was significantly associated with lower 3- and 6-month ADL levels (P < 0.001) and Delta DAS28 and PsARC response at 3, 6 and 12 months. Meanwhile, MTX co-therapy was associated with a reduction in immunogenicity at 3 and 6 months (P = 0.008 and P = 0.024). Conclusion Although both were associated with reduced response, the objectively measured non-trough drug levels showed more significant associations with drug response than self-reported non-adherence measures. Lay Summary What does this mean for patients? Psoriatic arthritis (PsA) is a long-term condition that affects a person's skin and joints, owing to inflammation. Despite a wide range of drugs being available, treatment fails to improve the control of the condition in up to 40% of people with PsA, and this includes advanced biologic therapies that target the immune system. This might be attributable to a person not taking their therapy as prescribed, low levels of the drug in their blood or the presence of anti-drug antibodies. Here, we measured drug levels of two commonly prescribed biologic therapies (adalimumab and etanercept). We asked patients to tell us whether they took their drugs as prescribed and explored the relationship with treatment response. We found that 36% of people reported not taking their drugs as they were advised (non-adherence), and this group were less likely to respond to therapy over 12 months. Meanwhile, people with lower adalimumab and etanercept drug levels were less likely to respond to therapy at multiple time points. There was no clear relationship between drug levels and whether a person said they took their drug or not in this study. Lifestyle factors, including a person's body mass index and presence of antibodies that deactivate the biologics (anti-drug antibodies), were also seen to impact treatment response. Taking a commonly prescribed drug, methotrexate, in addition to advanced biologic therapy was seen to reduce the presence of anti-drug antibodies. Overall, drug levels were more significantly associated with drug response compared with whether a person reported taking their therapy.