Abstract
BackgroundInfliximab (INX) and other tumour necrosis factor inhibitors (TNFi) have revolutionised the treatment of several immune mediated inflammatory diseases. Still, many patients do not respond sufficiently to therapy or lose efficacy over time. The large interindividual variation in serum drug concentrations on standard doses and the development of anti-drug antibodies are thought to be major reasons for treatment failures. Therapeutic drug monitoring (TDM), an individualised treatment strategy based on systematic assessments of serum drug concentrations, has been proposed as a clinical tool to optimise efficacy of INX treatment. TDM seems reasonable both from a clinical and an economical point of view, but the effectiveness of this treatment strategy has not yet been demonstrated in randomised clinical trials. The NORwegian DRUg Monitoring study (NOR-DRUM) aims to assess the effectiveness of TDM, both with regard to the achievement of remission in patients starting INX treatment (part A) as well as to maintain disease control in patients on INX treatment (part B).MethodsThe NOR-DRUM study is a randomised, open, controlled, parallel-group, comparative, multi-centre, national, superiority, phase IV study with two separate parts, NOR-DRUM A and NOR-DRUM B. Patients with rheumatoid arthritis, psoriatic arthritis, spondyloarthritis, ulcerative colitis, Crohn’s disease and psoriasis are included. In both study parts participants are randomised 1:1 to either TDM of infliximab (intervention group) or to standard treatment with infliximab without knowledge of drug levels or ADAb status (control group). NOR-DRUM A will include 400 patients starting INX therapy. The primary outcome is remission at 30 weeks. In NOR-DRUM B, 450 patients on maintenance treatment with INX will be included. The primary endpoint is occurrence of disease worsening during the 52-week study period.DiscussionAs the first trial to assess the effectiveness, safety and cost-effectiveness of TDM in patients receiving TNFi for a range of immune mediated inflammatory diseases, we hope that the NOR-DRUM study will contribute to the advancement of evidence based personalised treatment with biological medicines.Trial registrationClinicaltrials.gov, NCT03074656. Registered on 090317.
Highlights
Infliximab (INX) and other tumour necrosis factor inhibitors (TNFi) have revolutionised the treatment of several immune mediated inflammatory diseases
As the first trial to assess the effectiveness, safety and cost-effectiveness of Therapeutic drug monitoring (TDM) in patients receiving TNFi for a range of immune mediated inflammatory diseases, we hope that the NOR-DRUM study will contribute to the advancement of evidence based personalised treatment with biological medicines
One major reason for this interindividual variation is the development of anti-drug antibodies (ADAb) which occur in 10%–60% of patients on INX [9,10,11]
Summary
Overview of study design The NOR-DRUM study is a randomised, controlled, parallelgroup, open, comparative, multi-centre, national, superiority, phase IV study with two separate parts (NOR-DRUM A and NOR-DRUM B) comparing TDM of INX treatment to standard INX treatment. ALT alanine aminotransferase, ASDAS Ankylosing Spondylitis Disease Activity Score, BASDAI Bath Ankylosing Spondylitis Disease Activity Index, CD Crohn’s disease, CDAI Clinical Disease Activity Index, CRP C-reactive protein, DAS28 Disease Activity Score using 28 joints, DLQI Dermatology Life Quality Index, ESR erythrocyte sedimentation rate, HBI Harvey-Bradshaw Index, IBD inflammatory bowel diseases, IBDQ Inflammatory Bowel Disease Questionnaire, INX infliximab, MHAQ Modified Health Assessment Questionnaire, PASI Psoriasis Area and Severity Index, PMS partial Mayo score, Ps psoriasis, PsA psoriatic arthritis, PsAID Psoriatic Arthritis Impact of Disease, SDAI Simplified Disease Activity Index, RA rheumatoid arthritis, RAID Rheumatoid Arthritis Impact of Disease, SF-36 Short Form Health Survey, SpA spondyloarthritis, UC ulcerative colitis, VAS visual analogue scale the patient at risk of medical injury or there has been a major protocol violation. Patient-reported outcome measures (PROMs) and disability will be assessed using Short Form (36) Health Survey (SF-36) (generic), EuroQol 5 Dimensions (EQ-5D) (generic), MHAQ (RA, PsA, SpA), IBDQ (IBD) and DLQI (Ps) These scores will be summarised by descriptive summary tables at baseline and over time, and at the end of study.
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