Based on CORRONA data through 12/30/2009, a total of 22,966 RA patients were enrolled with 136,738 visits accrued. Overall, the prevalence of biologic agent use within CORRONA increased from 40% in 2003 to 62% in 2009 (). When subjects were categorized based on whether they are on their 1st, 2nd, 3rd or more biologic agents, the greatest amount of increase in the prevalence was observed among subjects receiving their 2nd–7th biologic agents. The level of disease activity at which patients switched gradually decreased over time (). In 2008 – 2009, patients who switched had a median CDAI between 10 and 15, slightly above the CDAI threshold for low disease activity.
Prevalence of biologic agent use in a large North American cohort of RA patients by calendar year and history of previous biologic agent use
Level of disease activity* at which RA patients switched their biologic treatment regimen, by calendar year
We identified 3,351 RA patients who initiated a new anti-TNF agent, and after applying the inclusion and exclusion criteria, 1,549 patients were eligible and they contributed 2,302 treatment episodes that were included in this analysis. Among these patients, 1,247 continued on the same treatment and 302 discontinued and/or switched to a different biologic agent within one year. Most (62%) of these patients were on their first anti-TNF treatment, 30% were on the second anti-TNF treatment, and 8% were on the third. At the time of treatment initiation, the average age was 56.1 (standard deviation, 12.9) and 80% were women.
At the follow-up visit within one year, maintainers had lower disease activity compared to switchers (median CDAI 8.4 vs. 15.2; mean DAS28 3.1 vs. 4.0) (). Maintainers also experienced a greater amount of improvement (reduction) in disease activity since treatment initiation (median change in CDAI −7.7 vs. −2.3, median change in DAS28 −1.1 vs. −0.3). Significant differences were also observed in tender and swollen joint counts, patient and physician global, pain, and mHAQ. On average, maintainers used a greater number of prior DMARDS compared to switchers. None of the laboratory measures (i.e. CRP and ESR) were significantly different between maintainers and switchers ().
Comparison of patient characteristics measured at time of biologic treatment regimen switch or the corresponding visit for those maintained on therapy
Stratifying patients by their baseline level of disease activity and RA disease duration, descriptive statistics measured at the follow-up visit suggested that the level of disease activity and the amount of improvement acceptable enough to continue patients on biologic treatment regimen was dependent on patients’ initial disease activity (). For example, for patients with disease duration ≥ 2 years, the median change in CDAI measured at the follow-up visit for patients who switched was 1.7 units (i.e. slight worsening), −1.3 units (slight improvement), and −9.6 units (some improvement) for those who started in low, moderate, and high baseline disease activity, respectively. Among those who remained on therapy, the median change in CDAI at the corresponding visits were −1.9, −7.1, and −20.0 units, respectively, demonstrating that physicians required differing levels of response in order to continue patients on therapy, conditional on where the patient started. Similar trends were observed with respect to patient and physician global and pain. Results were similar for those with RA disease duration < 2 years (data not shown).
Comparison of selected patient characteristics at time of biologic treatment regimen switch or the corresponding visit for those who were maintained on therapy among those with ≥ 2 years disease duration, by baseline disease activity level
After controlling for both the level of disease activity and the amount of improvement from baseline, calendar year was significantly associated with switching (). Compared to patients who initiated anti-TNF treatment between 2002 and 2005, the likelihood of switching was more than two folder greater in 2005–2006 (odds ratio [OR] = 2.62, 95% CI 1.64–4.19); this effect was even greater in 2008–2009 (OR = 6.05, 95% CI 3.72–9.86). There was a significant clustering effect by physician in the decision to switch (OR=1.32, 95%CI 1.16–1.95). Additionally, a significant interaction between calendar year at treatment initiation and disease activity was observed: the likelihood to switch among patients with moderate disease activity (CDAI between 10 and 22) was greater over calendar time compared to those with low or high disease activity (OR = 2.4, 95% CI 1.0 – 6.0).
Table 3 Multivariable Adjusted Association between Absolute Disease Activity, Change in Disease Activity, and Calendar Time with Switching the Biologic Treatment Regimen within the first year (A total of 2,070 treatment episodes; 272 switched and 1,798 maintained (more ...)
To examine whether the observed association between calendar time and switching biologics may be explained by changing patient characteristics over time, we have compared baseline patient characteristics across the three cohorts of patients including age, age at RA onset, disease duration, mHAQ, DAS28, CDAI, patient and physician global, and glucocorticoid use. The distributions of these characteristics were comparable (data not shown).
The sensitivity analysis that restricted the study population to only those who switched for physician designated reasons of lack of efficacy yielded a similar effect of calendar year (data not shown). The interaction between moderate disease activity and calendar year at treatment initiation was likewise stronger (OR=3.4, 95% CI 1.1 – 10.2). When those did not initiate another biologic agent after discontinuing the initial anti-TNF agent were excluded, the results were consistent with those from the main analysis, and the interaction between calendar time and moderate disease activity was similar (OR=5.7, 95% CI 1.1 – 30.4).
We identified a subgroup of 667 treatment episodes (159 switched and 508 maintained therapy) with sub-optimal response to their anti-TNF treatment (CDAI > 10 and change in CDAI > −10). After adjusting for comorbidities, level of disease activity, and calendar year, patients with a SJC/TJC ratio < 0.4 and higher (better) physician global were more likely to be maintained on the same therapy ().