Low-dose prednisolone treatment of early rheumatoid arthritis and late cardiovascular outcome and survival: 10-year follow-up of a 2-year randomised trial

Abstract

ObjectiveTo examine the long-term effects of early low-dose prednisolone use in patients with rheumatoid arthritis (RA) on cardiovascular (CV) morbidity and mortality.DesignRetrieval of data from a 2-year open randomised trial comparing prednisolone 7.5 mg/day in addition to disease-modifying antirheumatic drugs (DMARDs) with DMARD therapy alone. Participants were followed for 10 years since inclusion into the original prednisolone trial or until occurrence of the studied outcomes.SettingSecondary level of care; six participating centres from southern Sweden; both urban and rural populations.ParticipantsOverall, 223 patients with early RA were included. The participants had no history of CV events at baseline and incident cases were identified via the Swedish Hospital Discharge and Cause of Death Registries.OutcomesComposite CV events, that is, ischaemic coronary and cerebrovascular events, components of the composite CV outcome, and death. Relative HRs from Cox proportional-hazards regression models were calculated.ResultsWithin 2041 person-years, 17 incident composite CV events occurred in 112 patients (15%) randomised to prednisolone, and 15 events of 111 patients (14%) who were assigned not to receive prednisolone. There were nine deaths (8%) in each group. The age-adjusted relative hazards (HRs; 95% CI) for the first composite CV event, first coronary event and death in the prednisolone group versus the group not treated with prednisolone were 1.8 (0.9 to 3.6), 0.98 (0.4 to 2.6) and 1.6 (0.6 to 4.1), respectively. The risk for the first cerebrovascular event showed a 3.7-fold increased relative hazard (95% CI 1.2 to 11.4) among prednisolone treated patients.ConclusionsIn this inception cohort study of low-dose prednisolone use during the first 2 years of RA disease, the incidence of ischaemic coronary artery events was similar in the two treatment groups, whereas the long-term risk of ischaemic cerebrovascular events was higher in the prednisolone group. There was a trend towards reduced survival in the prednisolone group.Trial registration numberISRCTN20612367.

Seven-year tolerability profile of glucocorticoids use in early rheumatoid arthritis: data from the ESPOIR cohort

“…Most notably, two recent studies suggested a dose-dependent increase in mortality in RA27 28; del Rincón et al 27 revealed a daily threshold dose of 8 mg at which all-cause mortality increased with GC dose (adjusted HR=1.78; 95% CI 1.22 to 2.60), and in the German register Rheumatoid Arthritis oBservation of BIologic Therapy (RABBIT), use of GC >5 mg/day was associated with increased mortality risk, independent of RA activity 28. Moreover, a 10-year follow-up study examined cardiovascular events and deaths in early patients with RA with no history of CVD who were included in a recent open-label randomised trial of low-dose prednisolone (7.5 mg/day) over the first 2 years of early RA Better Anti-Rheumatic PharmacOTherapy (BARFOT+): low-dose prednisolone use was associated with increased incidence of cerebrovascular events and, although not significant, increased mortality 29. Long-term follow-up of Computer Assisted Management in Early Rheumatoid Arthritis (CAMERA II) patients with early RA who received prednisone at 10 mg/day for at least 2 years revealed increased cardiovascular risk and, although not significant, increased mortality 30…”

According to the Materials of the 2015/2016 New European League Against Rheumatism (Eular) Guidelines for Reducing Cardiovascular Risk in Patients With Inflammatory Arthritis: General Characterization and Discussion Problems

“…Доказан дозозависимый эффект ГК на повыше-ние вероятности развития ССО в группе больных с воспа-лительными артритами [36,108,109]. Длительное приме-нение ГК приводит к увеличению риска смертности.…”

The 2016 Eular Guidelines for the Diagnosis and Treatment of Early Arthritis

“…Обращается особое внимание на риск НР (инфекционных осложнений и кардиоваску-лярной патологии, увеличения массы тела, артериальной гипертензии, диабета, катаракты, остеопороза), который нарастает при достижении высокой кумулятивной дозы ГК и их длительном приеме [83][84][85][86][87][88][89][90][91].…”