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Cancer risk in patients with spondyloarthritis treated with TNF inhibitors: a collaborative study from the ARTIS and DANBIO registers
  1. Karin Hellgren1,2,
  2. Lene Dreyer3,4,
  3. Elizabeth V Arkema2,
  4. Bente Glintborg3,4,
  5. Lennart T H Jacobsson5,
  6. Lars-Erik Kristensen4,6,
  7. Nils Feltelius1,7,
  8. Merete Lund Hetland8,9,
  9. Johan Askling1,2
  10. For the ARTIS Study Group, For the DANBIO Study Group
    1. 1Rheumatology Unit, Department of Medicine, Solna, Karolinska Institutet at Karolinska University Hospital, Stockholm, Sweden
    2. 2Clinical Epidemiology Unit, Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden
    3. 3Department of Rheumatology, Herlev and Gentofte University Hospital, Hellerup, Denmark
    4. 4The Parker Institute, Bispebjerg and Frederiksberg, University of Copenhagen, Copenhagen, Denmark
    5. 5Department of Rheumatology and Inflammation Research, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
    6. 6Department of Rheumatology, Lund University Hospital, Lund, Sweden
    7. 7Swedish Medical Products Agency, Uppsala, Sweden
    8. 8DANBIO Registry, Center for Rheumatology and Spine Diseases, Centre for Head and Orthopaedics, Rigshospitalet, Glostrup, Denmark
    9. 9Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
    1. Correspondence to Dr Karin Hellgren, Rheumatology Unit, Department of Medicine, Solna, Karolinska Institutet at Karolinska University Hospital, 171 76 Stockholm, Sweden; karin.hellgren{at}karolinska.se

    Abstract

    Background Safety data on cancer risks following tumour necrosis factor α inhibitors (TNFi) in patients with spondyloarthritis (SpA) (here defined as ankylosing spondylitis (AS), undifferentiated spondarthropaties (SpA UNS), psoriatic arthritis (PsA)) are scarce. Our objective was to assess risks for cancer overall and for common subtypes in patients with SpA treated with TNFi compared with TNFi-naïve patients with SpA and to the general population.

    Methods From the Swedish (Anti-Rheumatic Therapy in Sweden (ARTIS)) and Danish (DANBIO) biologics registers, we assembled 8703 (ARTIS=5448, DANBIO=3255) patients with SpA initiating a first TNFi 2001–2011. From the Swedish National Patient and Population Registers we assembled a TNFi-naïve SpA cohort (n=28,164) and a Swedish age-matched and sex-matched general population comparator cohort (n=131 687). We identified incident cancers by linkage with the nationwide Swedish and Danish Cancer Registers 2001–2011, and calculated age-standardised and sex-standardised incidence ratios as measures of relative risk (RR).

    Results Based on 1188 cancers among the TNFi-naïve patients with SpA, RR of cancer overall was 1.1 (95% CI 1.0 to 1.2). Based on 147 cancers among TNFi initiators with SpA, RR versus TNFi-naïve was 0.8 (95% CI 0.7 to 1.0) and results were similar for AS and PsA when analysed separately. Site-specific cancer RRs: prostate 0.5 (95% CI 0.3 to 0.8), lung 0.6 (95% CI 0.3 to 1.3), colorectal 1.0 (95% CI 0.5 to 2.0), breast 1.3 (95% CI 0.9 to 2.0), lymphoma 0.8 (95% CI 0.4 to 1.8) and melanoma 1.4 (95% CI 0.7 to 2.6).

    Conclusions In patients with SpA, treatment with TNFi was not associated with increased risks of cancer, neither overall nor for the six most common cancer types.

    • Anti-TNF
    • Ankylosing Spondylitis
    • Psoriatic Arthritis
    • Spondyloarthritis
    • Outcomes research

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    Footnotes

    • Handling editor Tore K Kvien

    • KH, LD, MLH and JA shared authorships.

    • Collaborators The ARTIS Study Group (Eva Baecklund, Nils Feltelius, Alf Kastbom, Carl Turesson, Elisabeth Lindqvist, Lars-Erik Kristensen, Lennart T.H Jacobsson, Lars Klareskog, Helena Forsblad d'Elia, Solbritt Rantapää-Dahlqvist, Ronald van Vollenhoven). The DANBIO Study Group comprised the departments of rheumatology at the following hospitals in Denmark: Ålborg, Århus, Bispebjerg/Frederiksberg, Esbjerg, Fredericia, Gentofte/Herlev, Glostrup/Rigshospitalet, Gråsten, Hillerød, Hjørring, Holbæk, Holstebro, Horsens, Kolding, Odense, Randers, Roskilde/Køge, Rønne, Silkeborg, Slagelse, Svendborg, Vejle and Viborg. The Oak foundation and the Danish Cancer Society.

    • Contributors All authors have made substantial contributions to conception and design, acquisition of data or analysis and interpretation of data; drafting the article or revising it critically for important intellectual content and final approval of the version to be published.

    • Funding The ARTIS Study Group conducts scientific analyses using data from the Swedish Biologics Register (ARTIS) run by the Swedish Society for Rheumatology. For the maintenance of this register, the Swedish Society for Rheumatology has received funding, independent of the conduct of these scientific analyses, from Merck, BMS, Pfizer, AbbVie, SOBI, UCB, Astra Zeneca and Roche. DANBIO has an independent steering committee with representatives from the Danish Society of Rheumatology and the hospital owners. It handles the regulatory, practical, financial and scientific challenges of the registry. DANBIO is sponsored by the hospital owners (Danish Regions) and by the pharmaceutical companies that offer biological treatments in rheumatology (AbbVie, Bristol Myers Squibb, Hospira, Roche, MSD, UCB-Nordic, Pfizer). The sponsors have no influence on the registry set-up, data collection, data analysis or publication of results. This specific study further received funding from the Swedish Foundation for Strategic Research, The Danish Cancer Society and the Danish Rheumatism Association.

    • Competing interests LD has received speaking fees from MSD and UCB. LTHJ has received consultancy fees or speaker honoraria from Abbvie, Actavis, Celgene, Novartis and Pfizer. LEK has received fees for consultancy and/or speaking from Pfizer, Abbvie, MSD, Janssen, Novartis, Celgene and UCB. NF is employed by the Medical Products Agency. MLH has received research grants from AbbVie, Bristol Myers Squibb, Pfizer, MSD and UCB-Nordic. JA has received research grants from Pfizer and AstraZeneca.

    • Ethics approval Ethics approval was granted by the Regional Ethics Committee, Karolinska Institutet, Stockholm, Sweden.

    • Provenance and peer review Not commissioned; externally peer reviewed.

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