The Impact of Tobacco Smoking on the Effectiveness of Abatacept in Rheumatoid Arthritis: Data from a Paneuropean Analysis of RA Registries

Axel Finckh^1,2, Jacques Gottenberg³, M. Victoria Hernández⁴, Florenzo Iannone⁵, Elisabeth Lie⁶, Helena Canhao⁷, Karel Pavelka⁸, Carl Turesson⁹, Merete Lund Hetland¹⁰ and Xavier Mariette¹¹, ¹Rheumatology Division, University Hospital of Geneva, Geneva, Switzerland, ²Div of Rheumatology, University of Geneva, Geneva, Switzerland, ³Hautepierre, Strasbourg, France, ⁴Arthritis Unit, Rheumatology, Hospital Clinic, Barcelona, Spain, ⁵Interdisciplinary Department of Medicine (DIM), Rheumatology Unit, University of Bari, Bari, Italy, ⁶Dept. of Rheumatology, Diakonhjemmet Hospital, Oslo, Norway, ⁷Rheumatology Research Unit, Instituto de Medicina Molecular, Lisbon, Portugal, ⁸Institute of Rheumatology, Department of Rheumatology, 1st Faculty of Medicine, Charles University, Prague, Czech Republic, ⁹Lund University, Rheumatology, Dept. of Clinical Sciences,, Malmö, Sweden, ¹⁰Copenhagen Center for Arthritis Research (COPECARE), Center for Rheumatology and Spine Diseases, Rigshospitalet - Glostrup, University of Copenhagen, Denmark, Glostrup, Denmark, ¹¹Université Paris-Sud, AP-HP, Hôpitaux Universitaires Paris-Sud, Paris, France

Meeting: 2015 ACR/ARHP Annual Meeting

Date of first publication: September 29, 2015

Keywords: Abatacept, prognostic factors and tobacco use

Session Information

Date: Sunday, November 8, 2015

Title: Rheumatoid Arthritis - Small Molecules, Biologics and Gene Therapy

Session Type: ACR Poster Session A

Session Time: 9:00AM-11:00AM

Background/Purpose:

It has previously been shown that current smoking is a predictor of poor response to methotrexate or anti-TNF treatment in rheumatoid arthritis (RA). The impact of smoking for response to biologic DMARDs (bDMARDs) with different modes of action is not known. The objective of this study was to investigate the effect of smoking on the effectiveness of abatacept (ABA) in patients (pts) with RA.

Methods:

This is a pooled observational database analysis of 9 European RA registries (ARTIS-SE, ATTRA-CZ, BIOBADASER-ES, DANBIO-DK, GISEA-IT, NOR-DMARD-NO, ORA-FR, SCQM-CH, Reuma.PT). Inclusion criteria for this analysis were a diagnosis of RA, initiation of ABA and available information on current smoking status. The primary endpoint was ABA drug retention. A secondary endpoint was EULAR good or moderate response rate at one year, estimated by longitudinal interpolation (mixed linear model) and corrected for drug retention (Lundex¹).Time to discontinuation was defined as the time between drug initiation and last administration plus one dispensation interval. Drug retention was analyzed using a Cox proportional hazards model, adjusting for potential confounders, including calendar year of treatment initiation, patient demographics, country of origin and disease characteristics.

Results:

We identified 4476 pts initiating ABA with 7881 pt-years (PY) of follow-up, of whom 721 (16%) were current smokers, and 3755 were non-smokers. Smokers were significantly younger (mean age 55.2 versus 58.4 yrs, p<0.001), with shorter disease durations (10 vs 13 yrs, p<0.001), more often RF-positive (78% vs 73%, p=0.03), more commonly males (27.5% vs 17.8%, p<0.001), with lower disease activity at baseline (DAS28 4.6 vs 4.8, , p<0.01) and less prior bDMARD exposure (median number of past bDMARDs 1 vs 2, p<0.001). Smoking was associated with an increased risk of ABA discontinuation for any reason (crude median survival time of 1.67 yrs vs 1.99 yrs for non smokers, p=0.04, hazard ratio (HR) (95% CI): 1.12, (1.01-1.32)), even after adjusting for potential confounding factors (HR (95% CI): 1.17 (1.01-1.35), p=0.03). When examining the role of current smoking on specific causes of drug discontinuation, only discontinuations due to ineffectiveness were associated with smoking (crude HR: 1.17, p=0.03; adjusted HR 1.17, p=0.10), but not discontinuations due to adverse events (crude HR: 1.03, p=0.80; adjusted HR 1.17, p=0.38). The EULAR good or moderate response rates at one year were lower in smokers than in non-smokers (73% versus 84%) (p<0.001). The Lundex based on EULAR good or moderate response rates were also lower in smokers then in non-smokers (48% versus 56%). The effect of smoking on ABA effectiveness was not modified by country of origin.

Conclusion:

Data from this Pan-European registry analysis suggest that smoking is associated with a decreased effectiveness of ABA, with higher discontinuation rates and lower response rates, as has previously been reported for methotrexate and anti-TNF agents. The difference in drug retention was modest and mainly due to discontinuations related to ineffectiveness. The mechanisms underlying this association remain to be elucidated and unmeasured confounding cannot be ruled out.

¹ A&R 2006;54:600-6

Disclosure: A. Finckh, BMS, 2; J. Gottenberg, None; M. V. Hernández, None; F. Iannone, None; E. Lie, Abbvie, 8,UCB, 8,Abbvie, 5,Bristol-Myers Squibb, 5,Hospira, 5,Pfizer Inc, 5,UCB, 5; H. Canhao, None; K. Pavelka, BMS, 8,Abbvie, 8,UCB, 8,Roche Pharmaceuticals, 8,Amgen, 8,Pfizer Inc, 8,MSD, 8,Egis, 8; C. Turesson, None; M. Lund Hetland, None; X. Mariette, None.

To cite this abstract in AMA style:

Finckh A, Gottenberg J, Hernández MV, Iannone F, Lie E, Canhao H, Pavelka K, Turesson C, Lund Hetland M, Mariette X. The Impact of Tobacco Smoking on the Effectiveness of Abatacept in Rheumatoid Arthritis: Data from a Paneuropean Analysis of RA Registries [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/the-impact-of-tobacco-smoking-on-the-effectiveness-of-abatacept-in-rheumatoid-arthritis-data-from-a-paneuropean-analysis-of-ra-registries/. Accessed .

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