Prospective, Intervention, Multicenter, Non-Inferiority Study of Utility of Therapeutic Drug Monitoring with Respect to the Efficacy and Cost of Adalimumab Tapering in Patients with Rheumatic Diseases

Catalina Gómez Arango¹, Maria Luz Garcia Vivar², Eduardo Úcar Angulo¹, Iñigo Gorostiza³, Clara Eugenia Perez², Juan Ramon De Dios⁴, Belen Alvarez⁵, Ana Ruibal Escribano⁶, Claudia Stoye⁵, Margarida Vasques⁵, Joaquin Belzunegui Otano⁷, Antonio Escobar³, Ziortza Trancho⁸, Ainhoa Ruiz del Agua⁹, Lorena Del Rio⁹, Cristina Jorquera¹⁰, Antonio Martínez⁹ and Daniel Nagore⁹, ¹Rheumatology Department; Basurto University Hospital, Bilbao, Spain, ²RHEUMATOLOGY, Rheumatology Department; Basurto University Hospital, Bilbao, Spain, ³Research Unit, Basurto Univeristy Hospital, Bilbao, Spain, ⁴Rheumatology Department. Hospital Universitario de Araba, Vitoria, Spain, ⁵Rheumatology, Hospital Universitario de Araba, Vitoria, Spain, ⁶Rheumatology, Hospital Universitario de Araba, Vittoria, Spain, ⁷Donostia University Hospital, San Sebastian, Spain, ⁸Unidad de Investigación, Hospital Universitario de Basurto, Bilbao, Spain, ⁹R&D, Progenika-Grifols, Derio, Spain, ¹⁰Hospital Universitario de Basurto, Bilbao, Spain

Meeting: 2017 ACR/ARHP Annual Meeting

Date of first publication: September 18, 2017

Keywords: adalimumab and rheumatoid arthritis (RA), Biologics

Session Information

Date: Monday, November 6, 2017

Title: Rheumatoid Arthritis – Small Molecules, Biologics and Gene Therapy Poster II: Prognostic Factors, Imaging and Miscellaneous Reports

Session Type: ACR Poster Session B

Session Time: 9:00AM-11:00AM

Background/Purpose: Adalimumab (ADL) tapering based on clinical assessment is an usual practice, especially in patients in remission. The objective of INGEBIO was to analyze how personalized management guided by Therapeutic Drug Monitoring (TDM) in rheumatoid arthritis (RA), psoriatic arthritis (PsA) and ankylosing spondylitis (AS) patients impacts the annual direct costs to the Health System and the quality-adjusted life year (QALY) gained with respect to conventional practice in Spain. Second, to evaluate the effectiveness of TDM in the reduction of the number of days with high disease activity compared with conventional practice.

Methods: In a pragmatic, non-randomized, non-inferiority trial, adult patients treated with ADL (40 mg sc) who remained clinically stable for at least 6 months were recruited in 3 sites. Patients were grouped in Control (CG) and Intervention groups (IG) according to the site. ADL frequency was adjusted based on physician criteria. Patients are assessed at 8 visits for up to 18 months. Trough ADL and anti-ADL antibodies levels are measured with Promonitor-ADL and Promonitor-ANTI-ADL (Progenika). TDM data were released only to the IG, and blinded to the CG. Physicians in the IG were not obliged to follow any therapeutic algorithm based on TDM results but could use tests to alter doses based on their clinical judgement. Endpoints include DAS28, BASDAI, BASFI and HAQ-DI scores at every time point. Cost-effectiveness is evaluated according to associated costs and QALY.

Results: A total of 169 patients were recruited, but 19 were lost to follow-up (disease, N IG, N CG, %) (RA, 25, 29, 36.0%; PsA, 30, 18, 32.0%; and AS, 43, 5, 32.0%). Median disease duration was 124.0, 105.5 and 129.0 months for RA, PsA and AS, respectively. At baseline, 9 (17.3%) and 28 (28.6%) patients had low disease activity, 43 (82.7%) and 70 (71.4%) patients were in remission, and median trough ADL levels were 5.76 and 5.04 mg/L in the CG and IG, respectively. Mean follow-up (FU) was 544.6 and 530.8 days in the CG and IG, respectively. ADL doses were tapered in 18/52 (34.6%) and 35/98 (35.7%) patients in the CG and IG, respectively. Patients were in remission/low activity an average of 475.2 vs 460.2 days in the CG and IG, respectively. The number of flares in the CG and IG was 47 and 66, respectively. The rate of flares per patient-year of FU is 0.639 vs 0.463 in the CG and IG, respectively (a difference of -0.176; CI95%: -0.379 to 0.0289). The risk of flare is 27.5% lower in the IG (IRR= 0.7252; CI95%: 0.4997 to 1.0578). Median time to first flare was 136,5 and 145 days in the CG and IG, respectively. Quality of life (EQ-5D-5L) was significantly better in the IG at visits 2 (p=0.001) and 3 (p=0.035); EQ-5D-5L was higher (although not statistically significant) in the IG in the remaining visits. Mean QALY were 1.145 and 1.076 during FU per intervention and control patient, respectively (gain of 0.069). Average cost of Humira per patient-year was 10,664.54€ vs 9,856.45€ (-808.08€, 8% savings) in the CG and IG, respectively.

Conclusion: BDM-guided management is not inferior to clinically based management for maintaining remission after 18 months and is associated with fewer flares, better quality of life and lower treatment costs during the course of treatment.

Disclosure: C. Gómez Arango, None; M. L. Garcia Vivar, None; E. Úcar Angulo, None; I. Gorostiza, None; C. E. Perez, None; J. R. De Dios, None; B. Alvarez, None; A. Ruibal Escribano, None; C. Stoye, None; M. Vasques, None; J. Belzunegui Otano, None; A. Escobar, None; Z. Trancho, None; A. Ruiz del Agua, Progenika, 3; L. Del Rio, Progenika, 3; C. Jorquera, None; A. Martínez, Progenika, 3; D. Nagore, Procenika, 3.

To cite this abstract in AMA style:

Gómez Arango C, Garcia Vivar ML, Úcar Angulo E, Gorostiza I, Perez CE, De Dios JR, Alvarez B, Ruibal Escribano A, Stoye C, Vasques M, Belzunegui Otano J, Escobar A, Trancho Z, Ruiz del Agua A, Del Rio L, Jorquera C, Martínez A, Nagore D. Prospective, Intervention, Multicenter, Non-Inferiority Study of Utility of Therapeutic Drug Monitoring with Respect to the Efficacy and Cost of Adalimumab Tapering in Patients with Rheumatic Diseases [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 10). https://acrabstracts.org/abstract/prospective-intervention-multicenter-non-inferiority-study-of-utility-of-therapeutic-drug-monitoring-with-respect-to-the-efficacy-and-cost-of-adalimumab-tapering-in-patients-with-rheumati/. Accessed .

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