title: The effect of comedication with conventional synthetic disease modifying antirheumatic drugs on TNF inhibitor drug survival in patients with ankylosing spondylitis and undifferentiated spondyloarthritis: results from a nationwide prospective study.
abstract: OBJECTIVE
  To assess the effect of comedication with conventional synthetic disease modifying antirheumatic drugs (csDMARDs) on retention to tumour necrosis factor inhibitor (TNFi) therapy in patients with ankylosing spondylitis (AS) and undifferentiated spondyloarthritis (uSpA).
  
  
  METHODS
  Data on patients with a clinical diagnosis of AS or uSpA starting treatment with adalimumab, etanercept or infliximab as their first TNFi during 2003-2010 were retrieved from the Swedish national biologics register and linked to national population based registers. Five-year drug survival was analysed by Cox regression with age, sex, baseline csDMARD comedication, TNFi type, prescription year and covariates representing frailty and socioeconomic status. AS and uSpA were analysed separately. Sensitivity analyses included models with csDMARD as a time-dependent covariate and adjustments for additional potential confounders.
  
  
  RESULTS
  1365 patients with AS and 1155 patients with uSpA were included, of whom 40.8% versus 50.3% used csDMARD comedication at baseline. In the unadjusted analyses superior drug survival was observed for patients using versus not using csDMARD comedication among patients with AS (p<0.001) but not among patients with uSpA (p=0.175). In the multivariable Cox regression analyses comedication with csDMARD was associated with better retention to TNFi therapy both in AS (HR 0.71, p<0.001) and uSpA (HR 0.82, p=0.020). The results were similar with csDMARD comedication as a time-dependent covariate, and the associations were retained when adjusting for erythrocyte sedimentation rate, C-reactive protein, patient global, swollen joints, uveitis, psoriasis and inflammatory bowel disease.
  
  
  CONCLUSIONS
  In this large register study of patients with AS and uSpA, use of csDMARD comedication was associated with better 5-year retention to the first TNFi.
authors.affiliation: Department of Rheumatology and Inflammation Research, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden Department of Rheumatology, Diakonhjemmet Hospital, Oslo, Norway.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Lie
authors.affiliation: Section of Rheumatology, Department of Clinical Sciences, Lund University, Malmö, Sweden Musculoskeletal Statistics Unit, Department of Rheumatology, The Parker Institute, Copenhagen University Hospital, Bispebjerg and Frederiksberg, Copenhagen, Denmark.
authors.forename: Lars Erik
authors.initials: LE
authors.lastname: Kristensen
authors.affiliation: Department of Rheumatology and Inflammation Research, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
authors.forename: Helena
authors.initials: H
authors.lastname: Forsblad-d'Elia
authors.affiliation: Department of Rheumatology and Inflammation Research, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
authors.forename: Tatiana
authors.initials: T
authors.lastname: Zverkova-Sandström
authors.affiliation: Clinical Epidemiology Unit & Rheumatology Unit, Department of Medicine, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Johan
authors.initials: J
authors.lastname: Askling
authors.affiliation: Department of Rheumatology and Inflammation Research, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
authors.forename: Lennart T
authors.initials: LT
authors.lastname: Jacobsson
mesh_terms: D000068879:Adalimumab; D000328:Adult; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D000068800:Etanercept; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000627:therapeutic use*; D000069285:Infliximab; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use*; D008875:Middle Aged; D016016:Proportional Hazards Models; D011446:Prospective Studies; D018124:Receptors, Tumor Necrosis Factor / Q000627:therapeutic use*; D025241:Spondylarthritis / Q000188:drug therapy; D013167:Spondylitis, Ankylosing / Q000188:drug therapy*; D012460:Sulfasalazine / Q000627:therapeutic use*; D016019:Survival Analysis; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents; D007074:Immunoglobulin G; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D012460:Sulfasalazine; D000069285:Infliximab; D000068879:Adalimumab; D000068800:Etanercept; D008727:Methotrexate
keywords: Ankylosing Spondylitis; Anti-TNF; DMARDs (synthetic); Spondyloarthritis