Background Cigarette smoking is considered an established risk factor for the development of rheumatoid arthritis (RA) and for poor response in RA patients to treatment with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) and with anti-tumor necrosis factor (anti-TNF) agents [1,2].
Objectives This interim analysis of the German non-interventional study ICHIBAN (NCT01194401) assessed the effectiveness and safety of intravenously administered Tocilizumab (TCZ i.v.) with respect to patients' smoking status (smoker, ex-smoker, non-smoker).
Methods Since 2010 the ICHIBAN study collects clinical data of the routine use of TCZ i.v. in RA patients. The observation period for each patient is up to two years. At the due date of the current interim analysis (Dec 10, 2015) 2999 patients were enrolled. 902 patients have completed the maximal 104 weeks observation period (Group W104). Patients were subgrouped according to their smoking status at baseline (BL).
Results At BL the subgroups showed the following distribution: smokers 19.0%, non-smokers 52.5%, and ex-smokers 17.0%. The mean TCZ i.v. treatment duration was 1.7, 1.8, and 1.6 years, respectively, for the three groups.
In comparison to non-smokers and ex-smokers, smokers comprised a higher percentage of male patients, were younger, and showed shorter disease duration. Smokers showed slightly lower overall comorbidity rates, while COPD was observed almost three times more among smokers (3.5%) and ex-smokers (3.9%) than in non-smokers (1.3%). Concomitant use of csDMARDs and glucocorticoids (GC) was more frequent among smokers.
DAS28-ESR disease activity at BL was similar between the 3 subgroups. After 2 years TCZ i.v. therapy, disease activity was comparably decreased in all 3 groups. The mean reduction from BL in DAS28-ESR was 2.6 (smokers), 2.8 (non-smokers), and 2.5 (ex-smokers). At last visit, DAS28-ESR remission (<2.6) was reached by 48.0%, 52.3%, and 51.6% of patients, respectively The similar effectiveness of TCZ i.v. was also shown by patient reported outcomes via visual analogue scales (VAS).
Regarding safety, smokers showed higher event rates of adverse events (AE), serious adverse events (SAE), infections, and serious infections [Tab. 1]
Conclusions TCZ i.v. treatment over two years resulted in improvements of all disease activity parameters. Contrary to csDMARDs and TNF-blockers, the results show that smokers benefit from TCZ i.v. to the same extent as non-smokers and ex-smokers. The similar effectiveness of TCZ i.v. was confirmed by distinctly improved patient reported outcomes (PROs) in all subgroups. On the other hand, smoking seems to coincide with a higher rate of adverse events and an increased risk of infections. However, due to differences in baseline characteristics between the subgroups, this has to be interpreted with caution.
Chang K, et al. Int J Mol Sci. 2014 Dec 3;15(12):22279–95.
Theander E, et al. EULAR 2015: FRI0163.
Acknowledgements This study was funded by Roche/Chugai, Germany.
Writing assistance was provided by Ecron Acunova GmbH, Germany with support from Roche/Chugai.
Disclosure of Interest C. Specker Grant/research support from: Chugai, DRFZ, Consultant for: Abbvie, Janssen, Chugai, MSD, Novartis, UCB, Lilly, Boehringer, Speakers bureau: Abbvie, Celgene, Chugai, Euroimmun, MSD, Pfizer, UCB, H. Kellner: None declared, P. Kästner: None declared, C. Volberg: None declared, V. Braunewell: None declared, I. Schwarze: None declared, M. Aringer: None declared, M. Sieburg: None declared, M. Hofmann Employee of: Chugai Pharma Europe Ltd., Zweigniederlassung Deutschland, J. Flacke Employee of: Roche Pharma AG, Germany, H.-P. Tony Consultant for: Roche Pharma, Abbvie, BMS, Chugai, Janssen, Novartis, Pfizer, Sanofi, Lilly, MSD, Astra-Zeneca., G. Fliedner: None declared