Background Despite of the differences in the mode of action between abatacept (ABT) and cytokine-targeted biologics, accumulating clinical evidences have shown comparable clinical efficacy and effectiveness in patients with rheumatoid arthritis (RA). Therefore, the effect of ABT treatment on the serum cytokine profiles in RA patients needs to be elucidated.
Objectives To examine the association of serum cytokine levels at baseline or at follow-up with clinical and radiographic outcomes after ABT therapy.
Methods A total of 51 biologics-naive RA patients were enrolled in this cohort at the commencement of ABT. The levels of cytokines, including IL-6, TNFα, IL-1β, IL-2, IL-8, IL-10, IL-12p70, IFNγ and GM-CSF were quantified by a high-sensitivity, multi-cytokine, electrochemiluminescence assay at baseline (week 0), week 2, week 12 and week 24 after starting ABT. The relations between the levels of cytokines and clinical, functional and structural data were analyzed. At week 24, clinical remission was defined as DAS28 < 2.6, while radiographic remission as ΔTSS (van der Heijde-modified total Sharp score) ≤0.5.
Results The mean age of 51 patients was 65.8 years, and the mean disease duration of 8.6 years. The mean DAS28 decreased from 5.33 at week 0 to 3.66 at week 12 and 3.43 at week 24, respectively. Clinical and radiographic remissions at week 24 were achieved in 23.5% and 45.8% of patients, respectively. The levels of all 9 cytokines were not significantly altered during 24 weeks. Notably, radiographic remission at week 24 was significantly inversely correlated to the baseline serum IL-6 level (r=-0.34, p=0.0052 with logistic regression analysis). And 86.7% of patients with serum IL-6 ≤2.1 pg/ml at baseline showed radiographic remission, which was significantly higher than those with serum IL-6 >2.1 pg/ml at baseline (odds ratio=17.3, p=0.0001 with Pearson’s test). Interestingly, however, both the serum IL-6 levels at week 12 or week 24, and the time-averaged IL-6 during 24 weeks, as well as those values of other cytokines, were not significantly correlated with radiographic remission.
Conclusions High serum IL-6 level at baseline was identified as a risk for radiographic progression in RA patients receiving ABT. This may be partly explained by less potent inhibition of IL-6 production of ABT than anti-TNFα biological agents, suggesting different modes of action between those agents in terms of the effects on serum cytokines.
Disclosure of Interest J. Kikuchi Consultant for: Pfizer Japan Inc., H. Kameda: None Declared, K. Yoshimoto: None Declared, T. Takeuchi Grant/research support from: Abott Japan Co., LTD., Astellas Pharma, Bristol- Myers K.K., Chugai Pharmaceutical Co., LTD., Daiichi Sankyo Co., LTD., Eisai Co., LTD., Janssen Pharmaceutical K.K., Mitsubishi Tanabe Pharma Co., Nippon Shinyaku Co., LTD., Otsuka Pharmaceutical, Pfizer Japan Inc., Sanofi- aventis K.K., Santen Pharmaceutical, Takeda Pharmaceutical Co., LTD., Teijin Phrma Ltd., Consultant for: Astra Zeneca, K.K., Eli-Lilly Japan K.K., Novartis Pharma K.K., Mitsubishi Tanabe Pharma Co., Asahi Kasei Medical K.K., Speakers bureau: Abott Japan Co., LTD., Bristol-Myers K.K., Chugai Pharmaceutical Co., LTD., Eisai Co., LTD., Janssen Pharmaceutical K.K., Mitsubishi Tanabe Pharma Co., Pfizer Japan Inc., Takeda Pharmaceutical Co., LTD.