Current smoking strongly predicts rheumatoid arthritis radiographic progression

Current smoking at the time of early rheumatoid arthritis diagnosis was a strong risk factor for rapid radiographic progression in early rheumatoid arthritis, according to an analysis of patients in the multicenter, randomized SWEFOT trial.

Smoking emerged as an independent risk factor despite initial treatment with methotrexate, with or without subsequent adjunctive treatment with additional synthetic disease-modifying antirheumatic drugs or a biologic in nonresponders, wrote Dr. Saedis Saevarsdottir of the Karolinska Institute, Stockholm, and her associates in the trial’s study group.

The finding may be "perhaps not so surprising, since several older studies have previously reported an association between cigarette smoking and a more severe RA. ... [But] smoking habits have not been included in any of the recent studies on risk matrix of radiographic progression," she said.

The investigators identified 79 patients with radiographic progression among 311 patients in the trial who had radiographic data available at baseline and 1 year. Those who achieved a 28-joint disease activity score of less than 3.2 by 3-4 months remained on methotrexate (147 patients), whereas others were randomized again to add either infliximab (Remicade, 128 patients) or both sulfasalazine and hydroxychloroquine (130 patients). A total of 269 patients were included in a multivariable model (72 with radiographic progression) that included 80 who remained on methotrexate monotherapy, 94 who added infliximab, and 95 on triple therapy. The researchers defined radiographic progression as an increase in Sharp-van der Heijde score of 5 or greater after 1 year.

In the multivariable model, current smoking was the strongest baseline predictor of rapid radiographic progression (odds ratio, 2.78), and other independent predictors included erosions (OR, 2.21), C-reactive protein (CRP) level (OR, 1.49), and erythrocyte sedimentation rate (OR, 1.62) – all of which have been previously reported as baseline predictors of radiographic progression (Ann. Rheum. Dis. 2014 April 4 [doi:10.1136/annrheumdis-2013-204601]).

The investigators constructed a three-dimensional risk matrix for rapid radiographic progression based on their results with current smoking status, baseline erosions, and CRP level. At 1 year, 63% of patients who had all the predictors developed radiographic progression, compared with 12% of those without these three baseline predictors. The results were similar for men and women and within the different treatment subgroups. "Thus, the matrix may help to identify at baseline those patients at risk of radiographic progression, irrespective of which treatment is chosen on clinical grounds," the researchers wrote.

Two variables that had been significant predictors of radiographic progression in other studies and used in other risk matrices – swollen joint count and autoantibody positivity (rheumatoid factor and anti-cyclic citrullinated peptide antibodies [anti-CCP]) – were not independent predictors in the current study. In an exploratory analysis, the use of a lower Sharp-van der Heijde score cutoff of 1 or greater found both rheumatoid factor and anti-CCP positivity to be significant predictors of radiographic progression in unadjusted, but not adjusted, analyses. Tests of the current study’s risk matrix in anti-CCP negative and positive patients showed that current smokers with erosive disease had high risk for radiographic progression in both subsets of patients.

Data from the current study also performed "reasonably well" in a previous clinical trial–based risk matrix that had included autoantibody status instead of smoking status (Ann. Rheum. Dis. 2010;69:1333-7).

The study’s strength was its inclusion within a clinical trial of unselected early RA patients that reflects the common standard of care: giving methotrexate first, then adding a biologic or two additional synthetic disease-modifying antirheumatic drugs if low disease activity had not been achieved after 3-4 months of methotrexate monotherapy. Although patients’ pack-years of smoking were not available, the investigators noted that a previous study did not affect outcome when the smoking intensity was evaluated based on actual smoking status of current, past, or never smoker, "indicating that the actual smoking habits have most impact."

The study received no specific external funding. There were no relevant financial disclosures.

[email protected]

Current smoking at the time of early rheumatoid arthritis diagnosis was a strong risk factor for rapid radiographic progression in early rheumatoid arthritis, according to an analysis of patients in the multicenter, randomized SWEFOT trial.

Smoking emerged as an independent risk factor despite initial treatment with methotrexate, with or without subsequent adjunctive treatment with additional synthetic disease-modifying antirheumatic drugs or a biologic in nonresponders, wrote Dr. Saedis Saevarsdottir of the Karolinska Institute, Stockholm, and her associates in the trial’s study group.

The finding may be "perhaps not so surprising, since several older studies have previously reported an association between cigarette smoking and a more severe RA. ... [But] smoking habits have not been included in any of the recent studies on risk matrix of radiographic progression," she said.

The investigators identified 79 patients with radiographic progression among 311 patients in the trial who had radiographic data available at baseline and 1 year. Those who achieved a 28-joint disease activity score of less than 3.2 by 3-4 months remained on methotrexate (147 patients), whereas others were randomized again to add either infliximab (Remicade, 128 patients) or both sulfasalazine and hydroxychloroquine (130 patients). A total of 269 patients were included in a multivariable model (72 with radiographic progression) that included 80 who remained on methotrexate monotherapy, 94 who added infliximab, and 95 on triple therapy. The researchers defined radiographic progression as an increase in Sharp-van der Heijde score of 5 or greater after 1 year.

In the multivariable model, current smoking was the strongest baseline predictor of rapid radiographic progression (odds ratio, 2.78), and other independent predictors included erosions (OR, 2.21), C-reactive protein (CRP) level (OR, 1.49), and erythrocyte sedimentation rate (OR, 1.62) – all of which have been previously reported as baseline predictors of radiographic progression (Ann. Rheum. Dis. 2014 April 4 [doi:10.1136/annrheumdis-2013-204601]).

The investigators constructed a three-dimensional risk matrix for rapid radiographic progression based on their results with current smoking status, baseline erosions, and CRP level. At 1 year, 63% of patients who had all the predictors developed radiographic progression, compared with 12% of those without these three baseline predictors. The results were similar for men and women and within the different treatment subgroups. "Thus, the matrix may help to identify at baseline those patients at risk of radiographic progression, irrespective of which treatment is chosen on clinical grounds," the researchers wrote.

Two variables that had been significant predictors of radiographic progression in other studies and used in other risk matrices – swollen joint count and autoantibody positivity (rheumatoid factor and anti-cyclic citrullinated peptide antibodies [anti-CCP]) – were not independent predictors in the current study. In an exploratory analysis, the use of a lower Sharp-van der Heijde score cutoff of 1 or greater found both rheumatoid factor and anti-CCP positivity to be significant predictors of radiographic progression in unadjusted, but not adjusted, analyses. Tests of the current study’s risk matrix in anti-CCP negative and positive patients showed that current smokers with erosive disease had high risk for radiographic progression in both subsets of patients.

Data from the current study also performed "reasonably well" in a previous clinical trial–based risk matrix that had included autoantibody status instead of smoking status (Ann. Rheum. Dis. 2010;69:1333-7).

The study’s strength was its inclusion within a clinical trial of unselected early RA patients that reflects the common standard of care: giving methotrexate first, then adding a biologic or two additional synthetic disease-modifying antirheumatic drugs if low disease activity had not been achieved after 3-4 months of methotrexate monotherapy. Although patients’ pack-years of smoking were not available, the investigators noted that a previous study did not affect outcome when the smoking intensity was evaluated based on actual smoking status of current, past, or never smoker, "indicating that the actual smoking habits have most impact."

The study received no specific external funding. There were no relevant financial disclosures.

[email protected]

Current smoking at the time of early rheumatoid arthritis diagnosis was a strong risk factor for rapid radiographic progression in early rheumatoid arthritis, according to an analysis of patients in the multicenter, randomized SWEFOT trial.

Smoking emerged as an independent risk factor despite initial treatment with methotrexate, with or without subsequent adjunctive treatment with additional synthetic disease-modifying antirheumatic drugs or a biologic in nonresponders, wrote Dr. Saedis Saevarsdottir of the Karolinska Institute, Stockholm, and her associates in the trial’s study group.

The finding may be "perhaps not so surprising, since several older studies have previously reported an association between cigarette smoking and a more severe RA. ... [But] smoking habits have not been included in any of the recent studies on risk matrix of radiographic progression," she said.

The investigators identified 79 patients with radiographic progression among 311 patients in the trial who had radiographic data available at baseline and 1 year. Those who achieved a 28-joint disease activity score of less than 3.2 by 3-4 months remained on methotrexate (147 patients), whereas others were randomized again to add either infliximab (Remicade, 128 patients) or both sulfasalazine and hydroxychloroquine (130 patients). A total of 269 patients were included in a multivariable model (72 with radiographic progression) that included 80 who remained on methotrexate monotherapy, 94 who added infliximab, and 95 on triple therapy. The researchers defined radiographic progression as an increase in Sharp-van der Heijde score of 5 or greater after 1 year.

In the multivariable model, current smoking was the strongest baseline predictor of rapid radiographic progression (odds ratio, 2.78), and other independent predictors included erosions (OR, 2.21), C-reactive protein (CRP) level (OR, 1.49), and erythrocyte sedimentation rate (OR, 1.62) – all of which have been previously reported as baseline predictors of radiographic progression (Ann. Rheum. Dis. 2014 April 4 [doi:10.1136/annrheumdis-2013-204601]).

The investigators constructed a three-dimensional risk matrix for rapid radiographic progression based on their results with current smoking status, baseline erosions, and CRP level. At 1 year, 63% of patients who had all the predictors developed radiographic progression, compared with 12% of those without these three baseline predictors. The results were similar for men and women and within the different treatment subgroups. "Thus, the matrix may help to identify at baseline those patients at risk of radiographic progression, irrespective of which treatment is chosen on clinical grounds," the researchers wrote.

Two variables that had been significant predictors of radiographic progression in other studies and used in other risk matrices – swollen joint count and autoantibody positivity (rheumatoid factor and anti-cyclic citrullinated peptide antibodies [anti-CCP]) – were not independent predictors in the current study. In an exploratory analysis, the use of a lower Sharp-van der Heijde score cutoff of 1 or greater found both rheumatoid factor and anti-CCP positivity to be significant predictors of radiographic progression in unadjusted, but not adjusted, analyses. Tests of the current study’s risk matrix in anti-CCP negative and positive patients showed that current smokers with erosive disease had high risk for radiographic progression in both subsets of patients.

Data from the current study also performed "reasonably well" in a previous clinical trial–based risk matrix that had included autoantibody status instead of smoking status (Ann. Rheum. Dis. 2010;69:1333-7).

The study’s strength was its inclusion within a clinical trial of unselected early RA patients that reflects the common standard of care: giving methotrexate first, then adding a biologic or two additional synthetic disease-modifying antirheumatic drugs if low disease activity had not been achieved after 3-4 months of methotrexate monotherapy. Although patients’ pack-years of smoking were not available, the investigators noted that a previous study did not affect outcome when the smoking intensity was evaluated based on actual smoking status of current, past, or never smoker, "indicating that the actual smoking habits have most impact."

The study received no specific external funding. There were no relevant financial disclosures.

[email protected]