BRIGHTON, ENGLAND – Multiple factors predict whether patients with inflammatory polyarthritis will require treatment with a biologic agent, according to new data from the Norfolk Arthritis Register.
Indeed, younger age, ACPA (anti–citrullinated protein/peptide antibody) positivity, and inefficacy of the first nonbiologic disease-modifying antirheumatic drug, (DMARD) within the first 6 months were associated with a higher chance of requiring biologic treatment with an anti–tumor necrosis factor (TNF) drug or rituximab (Rheumatology [Oxford] 2011;50 [suppl. 3];iii37-9, abstract OP16).
However, none of these baseline predictors is included in the National Institute for Health and Clinical Excellence (NICE) guidelines for prescribing biologic therapy," said Dr. Suzanne Verstappen, who presented the findings at the annual meeting of the British Society for Rheumatology.
More than 800 patients who were enrolled in the Norfolk Arthritis Register (NOAR), a primary care–based inception cohort, were studied, reported Dr. Verstappen, a research fellow at the Arthritis Research UK Epidemiology Unit at the University of Manchester (England). Two groups of patients were identified: those who were recruited in the prebiologic era of 1990-1994 (n = 407), and those who were recruited in 2000-2004 (n = 416), after biologic agents had become widely available in the United Kingdom.
For inclusion in the analysis, all patients had to have at least two swollen joints for 4 or more consecutive weeks. They also had to have symptom duration of less than 24 months, failure to respond to at least one nonbiologic DMARD, and 1 year or more of available follow-up data.
At baseline, the mean age of patients was 53 years in the prebiologic cohort and 57 years in the postbiologic cohort, with women accounting for about 63% of the overall study population. The average symptom duration was 5.4 and 6.7 months, respectively, and the prebiologic-era group had more swollen (seven vs. three) and tender (seven vs. three) joints than did the postbiologic-era group. DAS28 (disease activity score based on a 28-joint count) assessments were also higher at baseline in the prebiologic-era group, compared with postbiologic-era patients (4.5 vs. 3.7), although their use of nonbiologic DMARDs was lower at baseline (34% vs. 65%).
At follow-up, a higher percentage of patients in the 2000-2004 cohort had started to use a biologic agent (10.8% vs. 7.9% for the 1990-1994 cohort). As would be expected, the time before starting a biologic agent for the first time was longer (almost 12 years) for those who were recruited before these agents became available; the later cohort of patients received biologic treatment 3.9 years after recruitment into NOAR.
The most common first biologic agent used in the earlier cohort of patients was infliximab (44%) with etanercept, adalimumab, and rituximab being used in 34%, 19%, and 3% of patients, which reflected the timing of their introduction into U.K. clinical practice. Patients who were recruited later were more likely to receive adalimumab (51%), followed by etanercept (27%) and infliximab (22%).
Patients in both groups had used at least three nonbiologic DMARDs before starting biologic treatment, and around half to two-thirds of patients had also used steroids.
"In both cohorts, ACPA positivity at baseline was the strongest baseline predictor" for receiving biologic therapy, Dr. Verstappen reported. Hazard ratios were 7.58 and 4.66 for the pre- and postbiologic-era groups, respectively.
Patients with two alleles of the shared epitope were also more likely to start biologic therapy early (HR, 3.42 and 3.25 for the pre- and postbiologic-era groups, respectively).
In the postbiologic-era group, younger age was also associated with earlier biologic agent use, compared with older patients (HR, 0.97). Patients in this group were also more likely to receive biologic treatment if they had failed treatment with their first nonbiologic DMARD. (Failure was defined as either stopping the nonbiologic DMARD because of inefficacy or needing a second agent within the first 6 months of treatment.)
Baseline disease activity measures were not associated with the need to receive biologic therapy, although the study did not evaluate cumulative disease activity over time.
"If we identify patients who are ACPA positive and those who have failed their first nonbiologic DMARD very early on in the disease, we could perhaps fast-track them to biologic therapy and reduce long-term disability," Dr. Verstappen concluded.
NOAR is funded by Arthritis Research UK. Dr. Verstappen stated that she had no conflicts of interest.