The Impact Of Inadequate Response To Prior Biologic Agents On Abatacept Drug Retention In Rheumatoid Arthritis Patients. A Pan-European Analysis Of RA Registries

Axel Finckh¹, Florenzo Iannone², Juan Gomez Reino³, David Neto⁴, Elisabeth Lie⁵, Piet van Riel⁶, Merete Lund Hetland⁷, Karel Pavelka⁸, Carl Turesson⁹, Xavier Mariette¹⁰ and Jacques-Eric Gottenberg¹¹, ¹Department of Medical Specialities, University of Geneva, Geneva, Switzerland, ²D.I.M.I.M.P, Rheumatology Unit - University of Bari, Bari, Italy, ³Rheumatology Department, Hospital Clínico de Santiago, Santiago de Compostela, Spain, ⁴Rheumatology, University of Geneva, Geneva, Switzerland, ⁵Rheumatology, Diakonhjemmet Hospital, Oslo, Norway, ⁶Rheumatology, Radboud University Nijmegen Medical Centre, Nijmegen, Netherlands, ⁷Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, The Danish Rheumatologic Database (DANBIO), Glostrup Hospital., Copenhagen, Denmark, ⁸Department of Clinical and Experimental Rheumatology, Charles University, Prague, Czech Republic, ⁹Lund University, Malmö, Sweden, ¹⁰Paris-Sud University, Paris, France, ¹¹Division of Rheumatology, University Hospital of Strasbourg, Strasbourg, France

Meeting: 2013 ACR/ARHP Annual Meeting

Keywords: Abatacept, Biologic drugs, drug therapy, registries and rheumatoid arthritis (RA)

Session Information

Title: Rheumatoid Arthritis Treatment - Small Molecules, Biologics and Gene Therapy I

Session Type: Abstract Submissions (ACR)

Background/Purpose:

In rheumatoid arthritis (RA), abatacept (ABA) may be used in biologic naïve patients (pts) or after failure to an anti-TNF or other biologic agents (BIO-IR). Drug retention is a useful overall measure of effectiveness, integrating both clinical response and tolerance. For several biologic antirheumatic agents (BIO), it has been demonstrated that a history of BIO-IR strongly decreases subsequent drug retention. The impact of BIO-IR has been less studied with ABA.

The objective of this study was to compare drug retention of ABA in BIO-IR pts.

Methods:

This is an observational cohort analysis of 8 prospective, longitudinal, European cohorts of RA pts (ARTIS (Sweden), ATTRA (Czech Republic), BIOBADASER (Spain), DANBIO (Denmark), GISEA (Italy), NORDMARDS (Norway), ORA (France), SCQM (Switzerland)). We included all RA pts treated with ABA in real life settings. The primary end point was drug retention of ABA. Secondary endpoint was ABA discontinuation for ineffectiveness. Time to discontinuation was defined as the time between drug initiation and last administration plus one dispensation interval. Drug discontinuation was analyzed using a Cox proportional hazards model, adjusting for potential confounders, such as calendar year of treatment initiation, patient demographics and disease characteristics.

Results:

We identified 3783 pts initiating ABA contributing 5980 patient-years of follow-up. Of these, 1159 pts were BIO-naïve, 883 pts had 1 prior BIO-IR, 861 pts had 2, 555 pts had 3 and 325 pts had 4 or more prior BIO-IRs. 85% of pts in the BIO-IR group had failed an anti-TNF agent as last biotherapy. Pts were mostly female (81%), with a mean age of 57 yrs, long disease durations (mean 12.1 yrs), and active, severe disease at baseline (mean values for DAS28: 5.1, ESR: 33 mm/hr, HAQ: 1.3).

In the 1977 ABA discontinuations, 72% were motivated by ineffectiveness, 24% by adverse events, 2% by remission and 2% by other reasons, when the reason for discontinuation was indicated. Drug retention differed significantly by prior BIO-IRs (p<0.001, logrank test). BIO-naïve pts had the highest drug retention (reference Hazard Ratio (HR): 1), pts with 1-3 prior BIO-IRs had lower retention (HR: 1.2-1.3, p<0.01), and pts with 4 or more BIO-IRs had the lowest retention (HR: 1.4, p < 0.001). A similar trend was observed when examining treatment discontinuation for ABA ineffectiveness (p< 0.001, logrank test). Drug discontinuation for ineffectiveness was uncommon in BIO-naïve pts (reference HR: 1), higher in pts with 1-2 prior BIO-IRs (HR: 1.2, p<0.05) and highest in pts with 3 or more BIO-IRs (HR: 1.5-1.6, p<0.01). Other strong predictors of drug retention were calendar year of ABA initiation, with significantly shorter drug retention in recent years (≤2007: HR=1; 2008-9: HR=1.2; ≥2010: HR: 2.2) and country of origin.

Conclusion:

Drug retention of ABA is strongly influenced by a history of prior BIO-IR, with higher discontinuation rates in pts having experienced more BIO-IRs, which suggests a progressive selection of pts with more resistant disease. However, some pts with a history of several BIO-IRs remained on ABA for an extensive time, suggesting some benefit of switching modes of action after anti-TNF-IR.

Disclosure:

A. Finckh,

BMS, Pfizer,

BMS, Abbvie, Roche, Pfizer,

Roche,,

F. Iannone,

BMS, Pfizer, Abbvie, UCB, Merck,

Roche, Actelion, Merck,

J. Gomez Reino,
None;

D. Neto,
None;

E. Lie,

Pfizer, Abbvie, Roche,

BMS, Pfizer, Abbvie, Roche,

P. van Riel,
None;

M. L. Hetland,

Roche Pharmaceuticals,

MSD, Pfizer,

K. Pavelka,

Roche, BMS, Pfizer, MSD, AbbVie,

C. Turesson,

Abbvie, Pfizer, Roche,

Abbvie, BMS, Janssen, MSD, Pfizer, Roche, UCB,

X. Mariette,

Pfizer, Roche,

BMD, GSK, LFB, Pfizer, Roche,

J. E. Gottenberg,

Pfizer, Roche,

Abbvie, BMS,MSD, Pfizer, Roche,

« Back to 2013 ACR/ARHP Annual Meeting

ACR Meeting Abstracts - https://acrabstracts.org/abstract/the-impact-of-inadequate-response-to-prior-biologic-agents-on-abatacept-drug-retention-in-rheumatoid-arthritis-patients-a-pan-european-analysis-of-ra-registries/