In this primary care-based inception cohort of patients with recent-onset IP who used at least one non-biological DMARD during follow-up, 7.9% of patients who were registered in the prebiological therapy era (cohort 1) and 10.8% of patients who were registered in the biological therapy era (cohort 2) received biological therapies within a median of 11.2 and 3.9 years from symptom onset, respectively. For patients in cohort 1, biological therapies only became available 5–10 years after registration in the NOAR cohort. Registration into cohort 2 started at approximately the same time as biological therapies became available in the UK. It, therefore, seems appropriate to show the results of these two cohorts separately.
A positive ACPA, measured at baseline, was the strongest predictor for starting biological therapy in both cohorts. The ACPA status was not known to the physician at the time treatment was started, and so cannot have directly influenced treatment decisions. Previous studies have shown that ACPA is a marker of disease severity10
and is strongly associated with joint damage,11–14
independent of RF status. The genetic contribution of SE to RA susceptibility15 16
and the production of ACPA17–19
is well established. The linkage between SE and disease progression has, however, been investigated less.20–22
In univariate analysis, but not multivariate regression analysis, we found in both cohorts that, compared with the carriage of no alleles of SE, carriers of two copies of SE were more likely to start biological therapy. Interestingly, we did not find an association between DAS28(3)CRP
or functional disability at baseline, factors often associated with a worse disease course, with the need to start biological therapy. We did not look at the cumulative disease activity, which may be an independent predictor for starting biological therapy.
Patients in cohort 2 who failed their first non-biological DMARD in the first 6 months due to inefficacy were more likely to receive biological therapy. This association is probably not observed in cohort 1 because biological therapy was not available until later in the disease. In a previous study from NOAR, we found that patients who discontinued their first treatment within 6 months experienced more deterioration in physical functioning in the long term.23
Given these findings, it may be appropriate to fast-track these patients for biological therapy as soon as they have failed their first non-biological DMARD for inefficacy.
Only one other study has looked at predictors of starting biological therapy. In the US ARAMIS database high levels of functional disability were associated with the initiation of biological therapy.6
In both the US study and our study, biological therapies were more often prescribed to younger patients. In general, there seems to be a trend towards less prescribing of non-biological DMARD and biological therapies in older patients,24 25
despite the fact that there is no difference in efficacy or tolerability of more aggressive treatment strategies in patients aged under 65 years than in those aged 65 years or older.26
This study comprised patients with IP recruited to a primary care-based inception cohort. Some people may argue that the disease course and applied treatment strategies may differ between patients with IP and RA and that biological therapy may only be prescribed to patients with RA. In our study population, 76/77 (98.7%) patients using biological therapy fulfilled the criteria for RA at some point during follow-up. However, some of these patients were not classified as having RA at baseline (33%), and when trying to identify predictors for the need to start biological therapy in patients with recent onset arthritis it is important to include all patients with IP in the analysis.
Overall, the factors identified in this study as predictors for receiving (or deciding to prescribe) biological therapy are a combination of factors associated with severe disease progression such as ACPA positivity, SE status, failure on the first non-biological DMARD and current smoking, plus demographic characteristics of the patients such as age and gender. Interestingly, none of these factors is included in the National Institute for Health and Clinical Excellence guidance for prescribing biological therapies in RA.