Early treatment of rheumatoid arthritis (RA) leads to improved long-term functional outcomes compared with later treatment (>6 months after symptom onset), according to a 20-year follow-up of patients included in the Norfolk Arthritis Register (Gwinnutt JM, et al. Arthritis Rheumatol. 2017 Apr 20. Epub ahead of print).
Although previous clinical trials have shown the benefits of early initiation of RA treatment over the short-term, few studies have evaluated long-term outcomes. One study, initiated in 1964, did not reflect modern treatment approaches. The 20-year data on patients initiating treatment in the early 1990s reflect advances in management over the past 2 decades, including the introduction of methotrexate (a conventional disease-modifying antirheumatic drug [DMARD]), as well as biologic DMARDs. Treatment strategies have also shifted toward initiating treatment early in the course of disease when there is a “window of opportunity” to affect the natural history of RA and improve outcomes.
“It was already known that early treatment was beneficial in the short-term. This study also emphasizes that it is important to treat patients with RA early, and that there are long-term benefits. These results emphasize again that early treatment is important, and early referral to a rheumatologist and early treatment will improve outcomes,” stated lead investigator Suzanne M. M. Verstappen, PhD, Senior Research Fellow, Arthritis Research UK Centre for Epidemiology, Centre for Musculoskeletal Research, School of Biological Sciences, University of Manchester, United Kingdom, in an interview with Value-Based Care in Rheumatology.
Dr Verstappen and colleagues had previously shown that patients treated within 6 months of symptom onset had improved 10-year outcomes compared with those who were treated later.
The present trial sought to define 20-year outcomes of patients with early RA, including mortality, disease activity, and physical function. The study included 602 patients with RA recruited for the Norfolk Arthritis Register between 1990 and 1994. At baseline, median symptom duration was 5.4 months, median age was 56 years, and 65.9% of participants were women.
Overall, 160 (26.6%) patients received treatment within 6 months of symptom onset (ie, early treatment group). Of these patients, 94 (58.8%) received sulfasalazine, 45 (28.1%) were prescribed steroids, 8 (5.0%) were prescribed methotrexate, and 13 (8.1%) were prescribed other DMARDs.
Of the remaining patients, 88 (19.9%) were given initial therapy 6 to 12 months following symptom onset, 77 patients (17.4%) 1 to 2 years following symptom onset, and 84 (19.0%) ≥2 years following symptom onset; 193 patients (43.7%) never received treatment during follow-up. Patients in the early treatment group were more likely to be men and have shorter disease duration at presentation than those who received treatment later. Patients who received early treatment also had worse clinical characteristics at baseline.
A 20-year assessment was performed on 207 (34.4%) patients. During the follow-up period, 205 (34.1%) patients died, 135 (22.4%) declined additional follow-up visits, 8 (1.3%) were ineligible after year 5, and 47 (7.8%) were lost to follow-up.
According to a multivariate Cox regression analysis, factors associated with increased risk for death included older age at symptom onset, male sex, and being a current smoker. For the total cohort, mean swollen and tender joint counts fell rapidly during the first year, and remained low during follow-up. Median Health Assessment Questionnaire scores fell initially, but increased after 2 years, culminating in a higher median score after year 7 compared with baseline. Initially, a higher proportion of patients were taking conventional DMARDs in the early treatment group, but the percentage was similar in both the early and late treatment groups by year 2 (55%-65%). Only 7.6% of patients took biologic DMARDs during the study, and they were evenly distributed in the 2 treatment groups. Functional disability was consistently higher in patients who received any treatment compared with those who did not.
After controlling for age and sex in an adjusted model accounting for confounding by indication, the early treatment group had similar disability compared with the never-treated group during follow-up, whereas patients treated later had significantly higher disability scores during follow-up.
“Considering treatment was provided 20 years ago, patients experienced relatively good long-term outcomes, including functional disability. After adjusting for the fact that patients with more severe disease activity would be prescribed certain therapies more often, there was no difference in functional disability between patients who received therapy within the first 6 months...and those who did not receive any treatment. We also found that patients who were treated in the first 6 months had a lower risk of death, although this result was not significantly different. These results indicate that early treatment is not only of significance in the short-term, but in the long-term as well,” Dr Verstappen concluded.