Data from the Dutch COBRA study show a normalization of rheumatoid arthritis (RA) mortality when compared to the general population after 23 years of follow-up. These findings confirm that early, intensive treatment of RA – which may include the use of glucocorticoids – offers long-term benefits.
Mortality in patients with RA is known to be higher than in the general population (See 1, 2, 3). The adverse effects (AEs) of the disease also take some time to show; they become apparent after more than a decade. Yet, it is was unknown whether early, intensive treatment is able to improve mortality rates. Research from the Combinatietherapie Bij Rheumatoïde Arthritis (COBRA) trial, a prospective cohort study of early RA, now shows that early RA treatment provides long-term effectiveness without causing undue harm (See 4). Patients with early RA (median disease duration 4 months) were treated with sulphasalazine monotherapy (n=79) or a combination of sulphasalazine, low-dose methotrexate, and initially high, step-down prednisolone (COBRA, n=76).
In 2010, after 11 years of follow-up, the COBRA follow-up study showed numerically lower mortality and a similar prevalence of comorbidity in patients with COBRA treatment compared to patients with initial sulphasalazine monotherapy. Also, the lower progression of joint damage suggested long-term disease modification (See 5).
In the current analysis presented at EULAR 2018, researchers investigated mortality in the COBRA trial cohort after 23 years. They compared this mortality to that of the general population in the Netherlands by using a reference sample of the general population matched for age and gender (data from Statistics Netherlands). The standardized mortality ratio (SMR) was used to compare the trial groups and the general population. Data for almost all COBRA patients (154/155) was available. The mean duration of follow-up in this cohort was 23 years (in patients alive in a range of 22-24 years). In total, 44 (28%) of all patients had died (SMR = 0.80 [95% CI: 0.59-1.06]). This number consists of 20/75 of COBRA patients (27%; SMR = 0.75; 0.47-1.14) and 24/79 of patients who used sulphasalazine (30%; SMR 0.85 [95% CI: 0.56-1.25]). This difference in mortality was not significant (P=0.61). Data from the reference sample of the general population (n=154) showed that 55 people (36%) had died. The positive trend for combined treatment over sulphasalazine decreased over time.
The author of the study, Professor Maarten Boers (VU University Medical Centre, Amsterdam, the Netherlands), commented on these results by stating that they confirm long-term benefits of early, intensive treatment of RA that includes the use of glucocorticoids. “What is also of importance,” he added, “is that this study is one of the first to show a normalization of RA mortality compared to the general population after 23 years of follow-up.” (See 1)
1. Poppelaars PBM, et al. Mortality of the COBRA early rheumatoid arthritis trial cohort after 23 years follow up. EULAR 2018; Amsterdam: Abstract OP0015.
2. Gabriel SE. The epidemiology of rheumatoid arthritis. Rheum Dis Clin North Am 2001;27:269-81.
3. Guedes C, et al. Mortality in rheumatoid arthritis. Rev Rhum Engl Ed 1999;66:492–8.
4. Boers M, et al. Randomized comparison of combined step-down prednisolone, methotrexate and sulfasalazine with sulphasalazine alone in early rheumatoid arthritis. Lancet 1997;350:309-18.
5. Van Tuyl LH, et al. Survival, comorbidities and joint damage 11 years after the COBRA combination therapy trial in early rheumatoid arthritis. Ann Rheum Dis 2010;69:807-12.