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Biologic Adherence and Drug Survival in RA Patients

A real-world rheumatoid arthritis (RA) cohort study from Israel shows significant variability of drug survival using biologic disease-modifying anti-rheumatics drugs (bDMARDs) and targeted synthetic DMARDs (tsDMARDs).

A total of 753 RA patients were drawn from in a large Israeli health maintenance organization and included both treatment-naïve (62%) and treatment-experienced RA patients who initiated treatment with bDMARDs and tofactinib between 2015–2018.

Patients received 1287 treatment courses of DMARDs including tofacitinib 24.2%, tocilizumab 17.5%, etanercept 16.0%, adalimumab 10.4%, abatacept 9.9%, rituximab 9.0%, golimumab 6.9%, certolizumab pegol 3.6%, infliximab 1.9%, and sarilumab 0.5%. DMARDs were suspended in over 50% of all treatment episodes. Treatment-naïve patients were slightly younger (54.3 vs. 56.6 yrs), had shorter disease duration (12 vs. 101.5, mos.), were more likely to use csDMARDs (81.5% vs. 51%), and less likely to be diagnosed with diabetes, chronic kidney disease, and osteoporosis (P < 0.05).

DMARD discontinuation was reduced with Older age but was increased with higher number of primary care visits and higher Charlson’s comorbidity scores. First line bDMARD (or tsDMARD) use was commonly fTNF-α inhibitors (53.1%), followed by the JAK inhibitor (21.5%), IL-6 inhibitors (14.6%), anti-CD20 (5.6%), and CTLA4-Ig (5.2%). TNF-α inhibitors were the most frequently used drug as second line (34.4%) and third line (28.5%) therapy.

For all drugs, adherence ranged between 63.9 % and 67.4% and was higher in those using injectable (vs oral) drugs, regardless of treatment-experience status. In both sub-groups, adherencewas highest for drugs taken every 1-3 mos. (73.2%). In treatment-naïve patients, GLM had the highest adherence (79%), followed by ETN (70%), with RTX having the lowest (35%). In treatment-experienced patients, adherence was best with IFX (95%) and the lowest for CTZ (50%).

Using etanercept survival as a referent, treatment suspension was significiantly increased with adalimumab (HR 1.68), certolizumab (HR 1.62), and rituximab (HR 2.72).

Kaplan–Meier curves showed drug survival to be better in treatment-naïve patients. Among treatment-naïve patients, TCZ had the highest survival rate at 12 months, while at 24 and 36 months it was second to GLM. The survival rates of ETN were similar to those of TCZ. Lower survival rates were observed for TOF, ABA, and GLM throughout the study follow-up period.

In treatment-experienced patients, TCZ, ETN, TOF, ABA, and GLM had the highest survival rates at 12 and 24 months. At 36 months, GLM, TOF, ABA, and TCZ had similar survival rates (between 20% and 30%). In both treatment-naive and treatment-experienced patients, ADA, IFX, and RTX showed the lowest survival.

Drug survival in the real-world may be the best combined measure of treatment efficacy and safety. Such data is need with the growing number of available biologic and non-biologic therapies for RA patients.

There are significant limitations to these analyses, thereby limiting the applicability of such findings.


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The author has no conflicts of interest to disclose related to this subject