Dose REduction Strategy Study of TNF inhibitors in Psoriatic arthritis and axial Spondyloarthritis patients.

Spondyloarthritis, notably psoriatic arthritis (PsA) and axial SpA (axSpA) can successfully be treated with Tumour Necrosis Factor inhibitors (TNFi) therapy. When patients are in low disease activity (LDA), the question arises whether patients may be able to maintain LDA with a lower dose or without TNFi, as overtreatment with TNFi is associated with risk for infections and higher costs. A few non-randomised studies have previously explored the possibility of disease activity guided dose reduction in PsA and axSpA, but data is scarce and evidence from randomised trials is lacking. Also, no cost-effectiveness analysis has been performed to provide insight into the potential cost savings of effective dose reduction of TNFi. In contrast, the safety and efficacy of disease activity guided dose reduction of TNFi have already been shown in Rheumatoid Arthritis (RA), and similar strategy trials in Crohns’ disease and psoriasis are ongoing in the Netherlands. The aim of this study is therefore to investigate whether a treat-to-target (T2T) strategy with tapering attempt of TNFi is non-inferior to a T2T strategy without tapering attempt in PsA and axSpA patients having LDA for at least 6 months. In addition, a cost-effectiveness analysis will be performed to assess the cost effectiveness between both groups.

The aim of the study is to compare the proportion of patients (for PsA and axSpA together) having LDA at 12 months between a T2T strategy with versus without tapering attempt against a pre-set non-inferiority margin of 20%.

3, 6, 9 and 12 months

The following dose reduction strategy will be adviced to rheumatologists: For patients allocated to the T2T strategy group with tapering attempt the TNFi dose will be reduced about one third by extending the interval every 3 months from 14 to 21 to 28 days for adalimumab and certolizumab, from 7 to 10 to 14 days for etanercept, from 4 to 6 to 8 weeks for golimumab, after which the TNFi will be stopped For infliximab, the interval will remain 8 weeks but the dose will be reduced every 3 months from 3 to 2.25 to 1.5 mg/kg bodyweight after which infliximab will be stopped When a persistent loss of response/flare occurs, the treatment is intensified to the last effective interval/dose. Patients allocated to the T2T strategy group without tapering attempt will continue treatment following a standardized protocol that is aimed to maintain LDA, at the discretion of the rheumatologist and patiënt. Patients will have a 12 month follow-up period, which will be extended by an additional 12 months observational period (total 24 months of follow-up).