Background Resistin is an adipocytokine related to insulin resistance, inflammation and arthritis (1).
Objectives We investigated if resistin is associated with the disease activity and inflammation in DMARD-naïve rheumatoid arthritis (RA) patients, if it possesses predictive value on the disease progression, and if TNFα is involved in these effects.
Methods Ninety patients with early, DMARD-naïve RA participated in the NEO-RACo study. The patients were treated for the first four weeks with a combination of methotrexate (max 25 mg/week), sulfasalazine (max 2 g/day), hydroxychloroquine (35 mg/kg/week), and prednisolone (7.5 mg/day) (FIN-RACo treatment strategy). Thereafter patients were randomized to receive either infliximab or placebo added on the combination therapy and infusions were given at weeks 4, 6, 10, 18 and 26. Patients were followed for 5 years. Human macrophage cell-line THP-1 was used to study the effects of resistin on TNFα production in the in vitro studies.
Results At baseline, resistin levels correlated with disease activity and inflammation measured as DAS28 and ESR: when the patients were divided in tertiles based on their plasma resistin levels at baseline, DAS score showed positive linearity (p for linearity =0.0072) and similarly, ESR levels increased linearly in resistin tertiles (p for linearity <0.001). During the first four weeks of treatment with FIN-RACo + placebo, a significant decrease in plasma resistin levels was observed and there was a similar decrease in the FIN-RACo + infliximab group.
The predictive value of baseline resistin was evaluated on the disease progression during the 5 years follow-up. Highest resistin predicted more rapid radiological progression in the FIN-RACo + placebo group as measured by change in Sharp-van der Heijde total score (Fig. 1A). However, the baseline resistin level was not predictive in relation to the remission rate. Interestingly, adding infliximab to the treatment delayed the radiological progression and there was no difference in the radiological progression in the FIN-RACo + infliximab group between the resistin tertiles (Fig. 1B). Resistin also increased TNFα production THP-1 macrophages in vitro.
Conclusions High resistin level at the baseline was linked to active inflammatory disease and predicted erosive disease progression. Further, resistin increased the production of TNFα in macrophages in the in vitro studies and infliximab treatment overcame the poor predictive value of high resistin levels in the NEO-RACo study suggesting that the effects of resistin are mediated by TNFα. High resistin concentration may be a useful marker to distinguish patients with risk for erosive disease, who respond better to treatment with a combination of DMARDs and TNFα-antagonists rather than with traditional DMARDs only.
M. Scotece, J. Conde, K. Vuolteenaho, A. Koskinen, V. Lόpez, J. Gόmez-Reino, F. Lago, E. Moilanen, O. Gualillo. Adipokines as drug targets in joint and bone disease. Drug Discov Today, in press 2014.
Acknowledgements The participating patients, research personnel and other members of NEO-RACo Study Group are greatly acknowledged.
Disclosure of Interest K. Vuolteenaho Consultant for: *, H. Kautiainen Consultant for: *, T. Möttönen Consultant for: *, P. Hannonen Consultant for: *, M. Korpela Consultant for: *, M. Kauppi Consultant for: *, O. Kaipiainen-Seppänen Consultant for: *, R. Luosujärvi Consultant for: *, R. Nieminen Consultant for: *, M. Leirisalo-Repo Consultant for: *, E. Moilanen Consultant for: *All authors have received consulting fees or honoraria from all or some of the following: Abbott, Actelion, Amgen, Astra-Zeneca, BMS, Ely Lilly, GSK, MSD, Mundipharma, Pfizer, Roche, Schering-Plough, Servier, UCB Pharma.
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