title: Association of the TNF-α G-308A polymorphism with TNF-inhibitor response in sarcoidosis.
abstract: Responsiveness to tumour necrosis factor (TNF) inhibitors has been associated with the TNF-α G-308A polymorphism in rheumatoid arthritis. The aim of this study was to examine the association between the presence of this polymorphism and the response to TNF inhibitors in patients with refractory sarcoidosis. Patients (n=111) who started TNF-inhibitor treatment (76 infliximab, 35 adalimumab) were followed for at least 1 year. The main symptoms in these patients were fatigue (n=100, 90.1%), small fibre neuropathy (n=91, 82.0%), pulmonary involvement (n=69, 62.2%), and/or uveitis (n=31, 27.9%). Patients were additionally genotyped for the presence of the TNF-α G-308A polymorphism. Treatment response was assessed using clinical outcome measures and questionnaires. Three-quarters (n=83, 74.8%) of the patients responded well. Of the patients without the variant A-allele 93.6% (73 out of 78, p<0.001) improved, while 30.3% (10 out of 33) of variant A-allele carriers responded favourably to TNF inhibitors. For patients with the GG-genotype, the probability of improving compared with remaining stable or deteriorating was three times higher (risk ratio 3.09, 95% CI 1.84-5.20). Sarcoidosis patients without the TNF-α -308A variant allele (GG-genotype) had a three-fold higher response to TNF inhibitors (adalimumab or infliximab). Further research is needed to evaluate the value of genotyping for the TNF-α G-308A polymorphism in order to tailor TNF-inhibitor treatment.
authors.affiliation: Central Diagnostic Laboratory, Maastricht University Medical Centre, Maastricht, The Netherlands.
authors.forename: Petal A
authors.initials: PA
authors.lastname: Wijnen
authors.affiliation: Dept of Interstitial Lung Diseases, Gelderse Vallei Hospital, Ede, The Netherlands.
authors.forename: Johanna P
authors.initials: JP
authors.lastname: Cremers
authors.affiliation: Dept of Epidemiology, Maastricht University, Maastricht, The Netherlands.
authors.forename: Patty J
authors.initials: PJ
authors.lastname: Nelemans
authors.affiliation: Dept of Ophthalmology, Maastricht University Medical Centre, Maastricht, The Netherlands.
authors.forename: Roel J
authors.initials: RJ
authors.lastname: Erckens
authors.affiliation: Dept of Neurology, Diaconessenhuis, Leiden, The Netherlands.
authors.forename: Elske
authors.initials: E
authors.lastname: Hoitsma
authors.affiliation: Dept of Rheumatology, University Medical Centre St. Radboud, Nijmegen, The Netherlands.
authors.forename: Tim L
authors.initials: TL
authors.lastname: Jansen
authors.affiliation: Central Diagnostic Laboratory, Maastricht University Medical Centre, Maastricht, The Netherlands.
authors.forename: Otto
authors.initials: O
authors.lastname: Bekers
authors.affiliation: Dept of Interstitial Lung Diseases, Gelderse Vallei Hospital, Ede, The Netherlands Dept of Toxicology, Maastricht University, Maastricht, The Netherlands m.drent@maastrichtuniversity.nl.
authors.forename: Marjolein
authors.initials: M
authors.lastname: Drent
mesh_terms: D000068879:Adalimumab; D000328:Adult; D000483:Alleles; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use; D005260:Female; D005838:Genotype; D006801:Humans; D007249:Inflammation; D000069285:Infliximab; D008297:Male; D008875:Middle Aged; D009422:Nervous System Diseases / Q000473:pathology; D011110:Polymorphism, Genetic; D011336:Probability; D013902:Radiography, Thoracic; D012507:Sarcoidosis / Q000188:drug therapy / Q000235:genetics*; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000235:genetics*; D014605:Uveitis / Q000150:complications / Q000175:diagnosis
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab; D000068879:Adalimumab