title: Smoking and pre-existing organ damage reduce the efficacy of belimumab in systemic lupus erythematosus.
abstract: OBJECTIVE
  Belimumab is the first biologic drug approved for Systemic Lupus Erythematosus (SLE). Here, we aimed to investigate the effects of belimumab on clinical and serologic outcomes, and sought to identify predictors of treatment response in three Swedish real-life settings.
  
  
  METHODS
  Fifty-eight patients were enrolled at initiation of belimumab and followed longitudinally for up to 53months. Surveillance outcomes included the SLE Disease Activity Index 2000 (SLEDAI-2K), 100mm Visual Analogue Scales for Physician's Global Assessment (PGA), fatigue, pain and general health, and the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI). Assessment of treatment response included the SLE responder index (SRI). B lymphocyte stimulator (BLyS) levels were determined using ELISA.
  
  
  RESULTS
  SLEDAI-2K (median baseline score: 8.0; IQR: 4.0-13.8), PGA and corticosteroid use decreased during therapy, and patients reported improvements on fatigue, pain, and general health (p<0.0001 for all). SDI scores remained stable (p=0.08). Patients with baseline SDI scores >1 showed decreased probability and prolonged time to attain SRI response (HR: 0.449; 95% CI: 0.208-0.967), as did current smokers compared with non-smokers (HR: 0.103; 95% CI: 0.025-0.427). In contrast, baseline BLyS levels ≥1.2ng/mL predicted increased probability and shorter time to attain SRI response (HR: 2.566; 95% CI: 1.222-5.387).
  
  
  CONCLUSIONS
  Disease activity and corticosteroid usage decreased, patient-reported outcomes improved, and no significant organ damage was accrued during follow-up. Smoking and organ damage predicted reduced treatment efficacy. These findings might contribute to a better selection of patients who are likely to benefit from belimumab.
authors.affiliation: Department of Medicine, Rheumatology Unit, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden. Electronic address: ioannis.parodis@karolinska.se.
authors.forename: Ioannis
authors.initials: I
authors.lastname: Parodis
authors.affiliation: Department of Clinical and Experimental Medicine, Rheumatology/Division of Neuro and Inflammation Sciences, Linköping University, Linköping, Sweden.
authors.forename: Christopher
authors.initials: C
authors.lastname: Sjöwall
authors.affiliation: Department of Clinical Sciences Lund, Rheumatology, Lund University, Lund, Sweden.
authors.forename: Andreas
authors.initials: A
authors.lastname: Jönsen
authors.affiliation: Department of Medicine, Rheumatology Unit, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Daniel
authors.initials: D
authors.lastname: Ramsköld
authors.affiliation: Department of Medicine, Rheumatology Unit, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Agneta
authors.initials: A
authors.lastname: Zickert
authors.affiliation: Department of Clinical and Experimental Medicine, Rheumatology/Division of Neuro and Inflammation Sciences, Linköping University, Linköping, Sweden.
authors.forename: Martina
authors.initials: M
authors.lastname: Frodlund
authors.affiliation: Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
authors.forename: Azita
authors.initials: A
authors.lastname: Sohrabian
authors.affiliation: Department of Medicine, Rheumatology Unit, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden; Service de Rhumatologie, Centre National de Référence pour les Maladies Auto-Immunes Systémiques Rares, Université de Strasbourg, Strasbourg, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Arnaud
authors.affiliation: Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
authors.forename: Johan
authors.initials: J
authors.lastname: Rönnelid
authors.affiliation: Department of Medicine, Rheumatology Unit, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Vivianne
authors.initials: V
authors.lastname: Malmström
authors.affiliation: Department of Clinical Sciences Lund, Rheumatology, Lund University, Lund, Sweden.
authors.forename: Anders A
authors.initials: AA
authors.lastname: Bengtsson
authors.affiliation: Department of Medicine, Rheumatology Unit, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Iva
authors.initials: I
authors.lastname: Gunnarsson
mesh_terms: D000328:Adult; D061067:Antibodies, Monoclonal, Humanized / Q000494:pharmacology*; D005260:Female; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000188:drug therapy* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D012720:Severity of Illness Index; D012907:Smoking / Q000009:adverse effects*; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; C511911:belimumab
keywords: BAFF; BLyS; Belimumab; Biologics; Systemic lupus erythematosus