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Patients with psoriatic arthritis who smoke have worse patient-reported disease features at baseline and don't respond as well as nonsmokers to anti-tumor necrosis factor (TNF) treatment, a Danish study found.

Current smokers had higher patient global scores on a 100-mm visual analog scale compared with patients who had never smoked (72 mm versus 68 mm), higher scores for fatigue (72 mm versus 63 mm), and worse functional status on the Health Assessment Questionnaire (1.1 versus 1, P<0.05 for all), according to Bente Glintborg, MD, of Copenhagen University Hospital, and colleagues.

They also had lower rates of response on the American College of Rheumatology (ACR) 20% and 50% improvement criteria at 6 months (24% versus 33% and 17% versus 24%, P<0.05 for both),

Patients who smoked also had shorter disease duration at the time of initiating anti-TNF therapy (3 years versus 5 years, P<0.01), "which may indicate a more aggressive disease course among smokers," they commented.

"The impact of smoking on disease activity and functional status is , but has scarcely been investigated in psoriatic arthritis," Glintborg and colleagues wrote.

To address this, they analyzed data from , which includes more than 90% of Danish patients receiving treatment with biologic medications.

The analysis included 1,388 patients with psoriatic arthritis who had begun treatment with etanercept (Enbrel), infliximab (Remicade), or adalimumab (Humira).

One third were current smokers, while 41% had never smoked and 26% had smoked in the past but had quit.

While smoking did influence patient-reported disease features, less effect was seen on objective measures such as swollen joint count (P=0.1) and C-reactive protein level (P=0.2).

When response was assessed according to the criteria of the European League Against Rheumatism (EULAR), 34% of never smokers had good responses compared with 23% of current smokers (P=0.01).

Responses were most pronounced among men, with EULAR good responses for never smokers being 42% compared with 24% of current smokers (P=0.002), and ACR 20 and 50 responses being seen in 41% versus 25% (P=0.01) and 32% versus 21% (P=0.05), respectively.

On univariate analyses, current smokers were less likely to achieve EULAR good responses and ACR 20, 50, and 70 responses, although on multivariate analysis the significant difference was seen only on EULAR good responses among men who were current smokers (OR 0.5, 95% CI 0.3-0.9, P=0.03).

Overall, treatment adherence was lower in current smokers, whose median time on treatment was 1.56 years compared with 2.43 years for patients who had never smoked (P=0.02).

On a univariate analysis, current smoking was associated with lower adherence to treatment (HR 1.29, 95% CI 1.08-1.55), though after adjustment for age, sex, disease duration, and year in which treatment began on a multivariate analysis, no significant differences were seen.

The researchers also considered the possible interaction between smoking and the individual type of TNF inhibitor, and found that current smokers were less likely to be adherent to treatment with infliximab (HR 1.62, 95% CI 1.06-2.48) and etanercept (HR 1.74, 95% CI 1.14-2.66), although not with adalimumab (HR 0.80, 95% CI 0.52-1.23).

Possible explanations for smoking's adverse impact on disease include increases in inflammatory cytokines such as TNF-alpha, interference with drug bioavailability, and alterations in absorption following injections.

The researchers also noted that patients who had stopped smoking more than 4 years before beginning treatment showed very similar rates of adherence to treatment as did those who had never smoked.

"This may illustrate a gradual normalization of pathological processes and smoking-related behavior, and is noteworthy, as tobacco smoking is a potentially modifiable lifestyle factor," they observed.

This potential reversibility of the negative influence of smoking on disease and treatment highlights the need for clinicians to encourage patients to quit, they also noted.

Limitations of the study included a lack of information about pack-years of smoking and about the effects of socioeconomic factors and comorbid disease.

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