Background/Purpose: To study the retention rate of the anti-TNF biologics in the treatment of rheumatic diseases and the associated factors for drug withdrawal

Methods: Data on the use of biological agents for the treatment of various rheumatological disorders in 14 public hospitals were collected prospectively.  Efficacy data, serious adverse events, withdrawal of biologics and reasons for withdrawal were collected at regular time intervals.  The cumulative retention rate of individual agent was studied by the Kaplan-Meier method and factors associated with drug withdrawal were studied by Cox regression.

Results: From 2005 to 2012, 1335 courses of anti-TNF biological agents in 991 patients with rheumatic diseases were used. There were 553 women and 438 men (mean age 44.9±13.9 years and duration of underlying disease 7.4±6.6 years).  Underlying rheumatic diseases were: rheumatoid arthritis(RA) (50%), spondyloarthropathy (SpA)(37%), psoriatic arthritis(PSA) (11%) and others (2%).  The initial choice of the anti-TNF biologics was: infliximab (IFX) (N=618, 46%), etanercept (ETN) (N=468, 35%), adalimumab (ADA) (N=208, 16%) and golimumab (GLM) (N=41, 3%). The dosages of the biologics used were: IFX (intravenous; 3-5mg/kg for RA, 5mg/kg for SpA and PSA), ETN (subcutaneous; 50mg/week or 25mg 2x/week), ADA (subcutaneous; 40mg every 2 weeks) and GLM (subcutaneous; 50mg every 4 weeks).  The mean duration of administration per course of biologic was 20.1±19.7 months.  692 (52%) courses of anti-TNF agents were abbreviated because of the following reasons: 238 (34%) lack /loss of efficacy (primary or secondary failure); 185 (27%) serious adverse events; 123 (18%) financial reasons; and 146 (21%) other or unspecified reasons.  The overall cumulative drug withdrawal rate (due to either lack /loss of efficacy or adverse events) at 12, 24 and 36 months was 28%, 39% and 46% for IFX, and 22%, 27% and 32% for ETN, and 23%, 27% and 34% for ADA, respectively (log rank test; p<0.005 between IFX and either ETN or ADA).  When drug withdrawal was broken down into that due to loss of efficacy and adverse events, data remained significant in favor of ETN to IFX.  The follow-up time of ADA users was significantly shorter than those of ETN, and there was no significantly difference in the withdrawal rates between ETN and ADA.  The commonest reasons for drug withdrawal because of serious adverse events were: allergic skin reaction (3.6%), infusion/injection site reactions (2.1%) and tuberculous infection (1.9%).  Among 26 patients who developed tuberculosis, 21 patients were IFX users, 4 were ETN users and 1 was GLM user.  Patients with RA had significantly lower drug retention rate than SpA or PSA patients (log rank test; p<0.05).  Cox regression analysis revealed that the anti-TNF agent used (IFX versus ETN/ADA/GLM; HR 1.46 [1.17-1.81]; p=0.001) and rheumatoid arthritis (vs other diagnoses; HR 1.47 [1.13-1.93]; p=0.005) was independent predictors for drug withdrawal due to inefficacy or serious adverse events after adjustment for age, sex and disease duration.

Conclusion:  Our Registry data reveals that IFX is associated with a significantly higher withdrawal rate for both loss of efficacy over time and the development of serious adverse events, in particular tuberculosis.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/retention-rate-of-the-anti-tnf-biologics-in-the-treatment-of-rheumatic-diseases-and-predictive-factors-for-drug-withdrawal-data-from-the-hong-kong-biologics-registry/