Drug survival of second biological DMARD therapy in patients with rheumatoid arthritis: a retrospective non-interventional cohort analysis

Abstract

Background: Since persistence to first biological disease modifying anti-rheumatic drugs (bDMARDs) is far from ideal in rheumatoid arthritis (RA) patients, many do receive a second and/or third bDMARD treatment. However, little is known about treatment persistence of the second-line bDMARD and it is specifically unknown whether the mode of action of such a treatment is associated with different persistence rates. We aimed to assess discontinuation-, re-initiation- or continuation-rates of a 2nd bDMARD therapy as well as switching-rates to a third biological DMARD (3rd bDMARD) therapy in RA patients.

Method: Analysis was based on German claims data (2010-2013). Patients were included if they had received at least one prescription for an anti-TNF and at least one follow-up prescription of a 2nd bDMARD different from the first anti-TNF. Patient follow-up started on the date of the first prescription for the 2nd bDMARD and lasted for 12 months or until a patient's death.

Results: 2667 RA patients received at least one anti-TNF prescription. Of these, 451 patients received a second bDMARD (340 anti-TNF, mean age 52.6 years; 111 non-anti-TNF, mean age 55.9 years). During the follow-up, 28.8% vs. 11.7% of the 2nd anti-TNF vs. non-anti-TNF patients (p < 0.001) switched to a 3rd bDMARD; 14.1% vs. 19.8% (p = 0.179) discontinued without re-start; 3.8% vs.1.8% (p = 0.387) re-started and 53.5 vs. 66.7% (p < 0.050) continued therapy. Patients in the non-anti-TNF group demonstrated longer drug survival (295 days) than patients in the anti-TNF group (264 days; p = 0.016). Independent variables associated with earlier discontinuation (including re-start) or switch were prescription of an anti-TNF as 2nd bDMARD (HR = 1.512) and a higher comorbidity level (CCI, HR = 1.112), whereas previous painkiller medication (HR = 0.629) was associated with later discontinuation or switch.

Conclusions: Only 56.8% of RA patients continued 2nd bDMARD treatment after 12 months; 60% if re-start was included. Non-anti-TNF patients had a higher probability of continuing 2nd bDMARD therapy.

Keywords: Anti-TNF; Continuation of bDMARD therapy; Rheumatoid arthritis; Switch of bDMARD therapy; bDMARD therapy.

Fig. 1

12-month drug survival of 2nd bDMARD therapy in RA patients. Shows 12-month drug survival of RA patients having initiated a 2nd bDMARD therapy. Patients died during the observation period were censored. Differences between patients having received an anti-TNF versus those having received a non-anti-TNF were analysed using Log-Rank tests

Fig. 2

Predictors of 2nd bDMARD drug discontinuation. Estimation was done using multivariable Cox regression analysis based on a backward inclusion methodology (all variables with p < 0.100 were included). The model was controlled for age, gender and previous prescribed medications (differentiated by 12 different ATC main groups). Excluded variables were: concomitant DMARD therapy, concomitant painkiller medication, concomitant corticosteroid medication, adverse events before index date as defined in Additional file 2. Results are shown as 95%-CIs