Downloaded from http://ard.bmj.com/ on March 31, 2015 - Published by group.bmj.com
ARD Online First, published on February 9, 2015 as 10.1136/annrheumdis-2013-205133 Clinical and epidemiological research
EXTENDED REPORT
Impaired response to treatment with tumour necrosis factor α inhibitors in smokers with axial spondyloarthritis Adrian Ciurea,1 Almut Scherer,2 Ulrich Weber,3 Pascale Exer,4 Jürg Bernhard,5 Giorgio Tamborrini,6 Myriam Riek,2 Rüdiger B Müller,7 Bettina Weiss,8 Michael J Nissen,9 Rudolf Kissling,8 Beat A Michel,1 Axel Finckh,9 on behalf of the Rheumatologists of Swiss Clinical Quality Management Program for Axial Spondyloarthritis Handling editor Tore K Kvien ▸ Additional material is published online only. To view please visit the journal online (http://dx.doi.org/10.1136/ annrheumdis-2013-205133). For numbered affiliations see end of article. Correspondence to Dr Adrian Ciurea, Department of Rheumatology, University Hospital Zurich, Gloriastrasse 25, Zurich CH-8091, Switzerland; [email protected] AC and AS contributed equally. Received 21 December 2013 Revised 23 December 2014 Accepted 6 January 2015
ABSTRACT Objectives To investigate the impact of smoking on the response to treatment with a first tumour necrosis factor inhibitor (TNFi) in patients with axial spondyloarthritis (axSpA) in a real-life cohort. Methods Patients fulfilling the Assessment of SpondyloArthritis international Society (ASAS) classification criteria for axSpA in the Swiss Clinical Quality Management Cohort were included in this study. The potential association between smoking status and differential response to TNFi in terms of the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and the Ankylosing Spondylitis Disease Activity Score (ASDAS) was analysed using multiple adjusted longitudinal mixed effect models. Binary response rates at 1 year were assessed with multiple adjusted logistic analyses. Results A first TNFi was initiated in 698 patients with axSpA with available smoking status and a baseline or follow-up BASDAI assessment, of which 490 (70%) had complete covariate data. In comparison to non-smokers, current smokers demonstrated significantly smaller reductions in BASDAI and ASDAS scores upon treatment with TNFi (0.75 BASDAI units and 0.69 ASDAS units less, p=0.005 and 0.001, respectively) for patients with elevated baseline C-reactive protein (CRP) level. This effect was numerically smaller in patients with normal CRP. The odds for reaching a 50% improvement in BASDAI response or the ASAS criteria for 40% improvement after 1 year were significantly lower in current smokers than in nonsmokers (0.54, 95% CI 0.31 to 0.95, p=0.03 and 0.43, 95% CI 0.24 to 0.76, p=0.004, respectively). Conclusions Current smoking is associated with an impaired response to TNFi in axSpA.
INTRODUCTION
To cite: Ciurea A, Scherer A, Weber U, et al. Ann Rheum Dis Published Online First: [ please include Day Month Year] doi:10.1136/annrheumdis2013-205133
The influence of smoking on the development of rheumatoid arthritis (RA) is well established,1 and several therapeutic agents, including tumour necrosis factor inhibitors (TNFi), have been shown to be less effective in smokers with RA.2–4 Smokers have also been shown to have a shorter treatment adherence and a poorer response to TNFi in psoriatic arthritis.5 The impact of tobacco use in patients with axial spondyloarthritis (axSpA) is only beginning to emerge. Smoking was associated with incident ankylosing spondylitis (AS) in a recent
longitudinal cohort study.6 In several cross-sectional analyses, smokers with AS and early axSpA showed increased levels of disease activity markers in comparison to non-smokers.7–10 Several predictors of good response have been identified after the introduction of TNFi to the therapeutic armamentarium in axSpA, but smoking was not among them: young age, short disease duration, male gender, elevated C-reactive protein (CRP), human leucocyte antigen (HLA)-B27 positivity, high baseline disease activity as assessed by the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), as well as good functional status and spinal mobility expressed by the Bath Ankylosing Spondylitis Functional Index (BASFI) and Bath Ankylosing Spondylitis Metrology Index (BASMI), respectively.11–15 The aim of our study was to investigate the effect of smoking on the response to TNFi in a large cohort of patients with axSpA.
METHODS Study population and design Patients recruited in the ongoing Swiss Clinical Quality Management Cohort for axSpA (SCQMaxSpA) were required to have a clinical diagnosis of AS or another form of SpA with predominantly axial disease according to the treating rheumatologist.16 Clinical and laboratory data were collected annually with the additional possibility to include data at intermediate visits.17 Smoking status was obtained through a patient questionnaire: nonsmoker, previous smoker or current smoker, without reference to the quantity (eg, pack-years). Data on physical activity at each visit were also collected as a standardised patient questionnaire indicating the type of training: (a) none, (b) weekly 1 h group flexibility exercises offered by the Swiss AS Association throughout Switzerland, (c) flexibility exercises at home, (d) training in a gym and (f ) other physical activity as training. The answer options for the frequency of training periods per week for exercise types c–e were 1–2x, 3–4x and 5–7x. The number of exercise sessions per week equalled the sum of the indicated exercise types (using the lower value of the indicated frequency interval). Therapeutic interventions after inclusion into SCQM were left to the discretion of the
Ciurea A, et al. Ann Rheum Dis 2015;0:1–8. doi:10.1136/annrheumdis-2013-205133
1
Copyright Article author (or their employer) 2015. Produced by BMJ Publishing Group Ltd (& EULAR) under licence.
Downloaded from http://ard.bmj.com/ on March 31, 2015 - Published by group.bmj.com
Clinical and epidemiological research treating rheumatologist. However, patients eligible for treatment with TNFi were preferentially enrolled because regulatory authorities have called for continuous monitoring of patients receiving biologics and rheumatologists can deduct the costs of biologics used to treat patients included in SCQM-axSpA from their global treatment expenditures. This was a longitudinal study within the SCQM-axSpA cohort analysing data collected between the start of data collection in January 2005 and the end of January 2014. The major inclusion criterion for this study was the fulfilment of the Assessment of SpondyloArthritis international Society (ASAS) 2009 classification criteria for axSpA18 with the following minor modifications as the cohort was initiated before publication of these criteria: the ASAS criterion ‘inflammatory back pain’ was defined as low back pain and morning stiffness for >3 months, improving with exercise but not relieved by rest, as well as age at onset
ARD Online First, published on February 9, 2015 as 10.1136/annrheumdis-2013-205133 Clinical and epidemiological research
EXTENDED REPORT
Impaired response to treatment with tumour necrosis factor α inhibitors in smokers with axial spondyloarthritis Adrian Ciurea,1 Almut Scherer,2 Ulrich Weber,3 Pascale Exer,4 Jürg Bernhard,5 Giorgio Tamborrini,6 Myriam Riek,2 Rüdiger B Müller,7 Bettina Weiss,8 Michael J Nissen,9 Rudolf Kissling,8 Beat A Michel,1 Axel Finckh,9 on behalf of the Rheumatologists of Swiss Clinical Quality Management Program for Axial Spondyloarthritis Handling editor Tore K Kvien ▸ Additional material is published online only. To view please visit the journal online (http://dx.doi.org/10.1136/ annrheumdis-2013-205133). For numbered affiliations see end of article. Correspondence to Dr Adrian Ciurea, Department of Rheumatology, University Hospital Zurich, Gloriastrasse 25, Zurich CH-8091, Switzerland; [email protected] AC and AS contributed equally. Received 21 December 2013 Revised 23 December 2014 Accepted 6 January 2015
ABSTRACT Objectives To investigate the impact of smoking on the response to treatment with a first tumour necrosis factor inhibitor (TNFi) in patients with axial spondyloarthritis (axSpA) in a real-life cohort. Methods Patients fulfilling the Assessment of SpondyloArthritis international Society (ASAS) classification criteria for axSpA in the Swiss Clinical Quality Management Cohort were included in this study. The potential association between smoking status and differential response to TNFi in terms of the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and the Ankylosing Spondylitis Disease Activity Score (ASDAS) was analysed using multiple adjusted longitudinal mixed effect models. Binary response rates at 1 year were assessed with multiple adjusted logistic analyses. Results A first TNFi was initiated in 698 patients with axSpA with available smoking status and a baseline or follow-up BASDAI assessment, of which 490 (70%) had complete covariate data. In comparison to non-smokers, current smokers demonstrated significantly smaller reductions in BASDAI and ASDAS scores upon treatment with TNFi (0.75 BASDAI units and 0.69 ASDAS units less, p=0.005 and 0.001, respectively) for patients with elevated baseline C-reactive protein (CRP) level. This effect was numerically smaller in patients with normal CRP. The odds for reaching a 50% improvement in BASDAI response or the ASAS criteria for 40% improvement after 1 year were significantly lower in current smokers than in nonsmokers (0.54, 95% CI 0.31 to 0.95, p=0.03 and 0.43, 95% CI 0.24 to 0.76, p=0.004, respectively). Conclusions Current smoking is associated with an impaired response to TNFi in axSpA.
INTRODUCTION
To cite: Ciurea A, Scherer A, Weber U, et al. Ann Rheum Dis Published Online First: [ please include Day Month Year] doi:10.1136/annrheumdis2013-205133
The influence of smoking on the development of rheumatoid arthritis (RA) is well established,1 and several therapeutic agents, including tumour necrosis factor inhibitors (TNFi), have been shown to be less effective in smokers with RA.2–4 Smokers have also been shown to have a shorter treatment adherence and a poorer response to TNFi in psoriatic arthritis.5 The impact of tobacco use in patients with axial spondyloarthritis (axSpA) is only beginning to emerge. Smoking was associated with incident ankylosing spondylitis (AS) in a recent
longitudinal cohort study.6 In several cross-sectional analyses, smokers with AS and early axSpA showed increased levels of disease activity markers in comparison to non-smokers.7–10 Several predictors of good response have been identified after the introduction of TNFi to the therapeutic armamentarium in axSpA, but smoking was not among them: young age, short disease duration, male gender, elevated C-reactive protein (CRP), human leucocyte antigen (HLA)-B27 positivity, high baseline disease activity as assessed by the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), as well as good functional status and spinal mobility expressed by the Bath Ankylosing Spondylitis Functional Index (BASFI) and Bath Ankylosing Spondylitis Metrology Index (BASMI), respectively.11–15 The aim of our study was to investigate the effect of smoking on the response to TNFi in a large cohort of patients with axSpA.
METHODS Study population and design Patients recruited in the ongoing Swiss Clinical Quality Management Cohort for axSpA (SCQMaxSpA) were required to have a clinical diagnosis of AS or another form of SpA with predominantly axial disease according to the treating rheumatologist.16 Clinical and laboratory data were collected annually with the additional possibility to include data at intermediate visits.17 Smoking status was obtained through a patient questionnaire: nonsmoker, previous smoker or current smoker, without reference to the quantity (eg, pack-years). Data on physical activity at each visit were also collected as a standardised patient questionnaire indicating the type of training: (a) none, (b) weekly 1 h group flexibility exercises offered by the Swiss AS Association throughout Switzerland, (c) flexibility exercises at home, (d) training in a gym and (f ) other physical activity as training. The answer options for the frequency of training periods per week for exercise types c–e were 1–2x, 3–4x and 5–7x. The number of exercise sessions per week equalled the sum of the indicated exercise types (using the lower value of the indicated frequency interval). Therapeutic interventions after inclusion into SCQM were left to the discretion of the
Ciurea A, et al. Ann Rheum Dis 2015;0:1–8. doi:10.1136/annrheumdis-2013-205133
1
Copyright Article author (or their employer) 2015. Produced by BMJ Publishing Group Ltd (& EULAR) under licence.
Downloaded from http://ard.bmj.com/ on March 31, 2015 - Published by group.bmj.com
Clinical and epidemiological research treating rheumatologist. However, patients eligible for treatment with TNFi were preferentially enrolled because regulatory authorities have called for continuous monitoring of patients receiving biologics and rheumatologists can deduct the costs of biologics used to treat patients included in SCQM-axSpA from their global treatment expenditures. This was a longitudinal study within the SCQM-axSpA cohort analysing data collected between the start of data collection in January 2005 and the end of January 2014. The major inclusion criterion for this study was the fulfilment of the Assessment of SpondyloArthritis international Society (ASAS) 2009 classification criteria for axSpA18 with the following minor modifications as the cohort was initiated before publication of these criteria: the ASAS criterion ‘inflammatory back pain’ was defined as low back pain and morning stiffness for >3 months, improving with exercise but not relieved by rest, as well as age at onset
