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Smoking paradox in the development of psoriatic arthritis among patients with psoriasis: a population-based study
  1. Uyen-Sa D T Nguyen1,2,
  2. Yuqing Zhang2,3,
  3. Na Lu2,3,
  4. Qiong Louie-Gao2,
  5. Jingbo Niu2,4,
  6. Alexis Ogdie5,
  7. Joel M Gelfand5,
  8. Michael P LaValley2,
  9. Maureen Dubreuil2,
  10. Jeffrey A Sparks6,
  11. Elizabeth W Karlson6,
  12. Hyon K Choi2,3
  1. 1 Department of Orthopedics and Physical Rehabilitation, University of Massachusetts Medical School, Massachusetts, USA
  2. 2 Department of Medicine, Clinical Epidemiology Research and Training Unit, Boston University School of Medicine, Massachusetts, USA
  3. 3 Division of Rheumatology, Massachusetts General Hospital, Harvard Medical School, Massachusetts, USA
  4. 4 Department of Medicine, Baylor Medical School, Houston, Texas, USA
  5. 5 Departments of Medicine, Dermatology, Biostatistics and Epidemiology, Perelman School of Medicine-University of Pennsylvania, Philadelphia, Pennsylvania, USA
  6. 6 Department of Medicine, Division of Rheumatology, Immunology and Allergy, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, USA
  1. Correspondence to Dr Uyen-Sa D T Nguyen, Department of Orthopedics and Physical Rehabilitation, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655, USA; uyensa.nguyen{at}


Objectives Smoking is associated with an increased risk of psoriatic arthritis (PsA) in the general population, but not among patients with psoriasis. We sought to clarify the possible methodological mechanisms behind this paradox.

Methods Using 1995–2015 data from The Health Improvement Network, we performed survival analysis to examine the association between smoking and incident PsA in the general population and among patients with psoriasis. We clarified the paradox using mediation analysis and conducted bias sensitivity analyses to evaluate the potential impact of index event bias and quantify its magnitude from uncontrolled/unmeasured confounders.

Results Of 6.65 million subjects without PsA at baseline, 225 213 participants had psoriasis and 7057 developed incident PsA. Smoking was associated with an increased risk of PsA in the general population (HR 1.27; 95% CI 1.19 to 1.36), but with a decreased risk among patients with psoriasis (HR 0.91; 95% CI 0.84 to 0.99). Mediation analysis showed that the effect of smoking on the risk of PsA was mediated almost entirely through its effect on psoriasis. Bias-sensitivity analyses indicated that even when the relation of uncontrolled confounders to either smoking or PsA was modest (both HRs=~1.5), it could reverse the biased effect of smoking among patients with psoriasis (HR=0.9).

Conclusions In this large cohort representative of the UK general population, smoking was positively associated with PsA risk in the general population, but negatively associated among patients with psoriasis. Conditioning on a causal intermediate variable (psoriasis) may even reverse the association between smoking and PsA, potentially explaining the smoking paradox for the risk of PsA among patients with psoriasis.

  • smoking
  • psoriatic arthritis
  • epidemiology

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  • Handling editor Tore K Kvien

  • Contributors Study conception/design: USDTN, YZ and HKC. Data coding/analysis: USDTN, NL, QLG and MD. Manuscript drafting: USDTN, YZ and HKC. All authors substantially contributed to the data interpretation, manuscript revising, critical review and final approval.

  • Funding This current study was partly funded by the American College of Rheumatology RRF Investigator Award, the NIH NIAMS K01AR064351, K23 AR069668, K24AR064310 and P60AR047785. The funders had no involvement in the study design; in the collection, analysis, or interpretation of the data; in the writing of the report; or in the decision to submit the article for publication.

  • Competing interests None declared.

  • Ethics approval Institutional Review Board from the University of Massachusetts and Boston University Medical Schools.

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

  • Data sharing statement THIN is a licensed proprietary database from IMS Health Real World Evidence Solutions.