Study of Potential Clinical and Biologic Predictors of Maintaining Good Response at 1 Year Follow-up, in Patients with Ankylosing Spondylitis Under Dose Reduction of TNFi Treatment

Mireia Moreno¹, Caridad Pontes², Ferran Torres³, Agusti Sellas-Fernandez⁴, Miriam Almirall⁵, Juan Carlos Torre-Alonso⁶, Teresa Clavaguera⁷, Carlos Rodriguez-Lozano⁸, Luis Francisco Linares⁹, Ana Urruticoechea-Arana¹⁰, Eduardo Collantes-Estevez¹¹, Rosa Morla¹², Delia Reina¹³, Eduardo Cuende¹⁴, Pedro Zarco¹⁵, Cruz Fernandez-Espartero¹⁶, Rosario García-Vicuña¹⁷, Jesus Sanz¹⁸, Xavier Juanola¹⁹, Antoni Vallano²⁰, Francisco J Blanco²¹, Raimon Sanmarti²², Gonzalo Calvo²³, Cristina Avendaño²⁴, Eugenio De Miguel²⁵, Roser Vives²⁶, Raul Veroz Gonzalez²⁷, Carlos Alberto Montilla-Morales²⁸ and Jordi Gratacos-Masmitja²⁹, ¹Rheumatology, Parc Tauli Hospital Universitari, Sabadell, Spain, ²Clinic Pharmacology, Parc Tauli Hospital Universitari. I3PT. UAB, Sabadell, Spain, ³Hospital Clinic de Barcelona, Barcelona, Spain, ⁴Rheumatology, Hospital Universitario Valle Hebron, Barcelona, Spain, ⁵Rheumatology, Hospital del Mar, Barcelona, Spain, ⁶H Monte Naranco, Oviedo, Spain, ⁷Rheumatology. Palamós Hospital, Rheumatologist, Catalonia, Spain, ⁸Rheumatology, Hospital Universitario Dr. Negrin, Gran Canaria, Spain, ⁹Rheumatology, Hospital Virgen de la Arrixaca. Murcia. Spain, Murcia, Spain, ¹⁰Rheumatology Department. Hospital Can Misses, IBIZA, Spain, ¹¹Rheumatology, IMIBIC-Hospital Universitario Reina Sofia, Cordoba, Spain, ¹²Rambla Vella, 14, Hospital La Tecla, Tarragona, Spain, ¹³Rheumatology, Hospital de Sant Joan Despí Moisès Broggi, Barcelona, Spain, ¹⁴University Hospital Príncipe de Asturias, Immune System Diseases, Rheumatology department, Alcalá de Henares, Madrid, Spain, ¹⁵H Fundación Alcorcón, Alcorcón, Spain, ¹⁶Rheumatology, Hospital de Mostoles, Madrid, Spain, ¹⁷Rheumatology, Hospital Universitario de La Princesa. IIS La Princesa, Madrid, Spain, ¹⁸Rheumatology, Hospital Universitario Puerta de Hierro Majadahonda, Madrid, Spain, ¹⁹Rheumatology, Hospital Universitario de Bellvitge, Barcelona, Spain, ²⁰Clinic pharmacology, Hospital Universitari Bellvitge, Barcelona, Spain, ²¹Servicio de Reumatología. Area Genomica. Instituto de Investigación Biomédica de A Coruña (INIBIC). Complexo Hospitalario Universitario de A Coruña (CHUAC), Sergas. Universidade da Coruña (UDC), A Coruña, Spain, ²²Arthritis Unit, Rheumatology Dpt, Hospital Clinic of Barcelona, Barcelona, Spain, ²³Clinic pharmacology, Hospital Clinic Barcelona, Barcelona, Spain, ²⁴Clinic pharmacology, Hospital Puerta de Hierro, Madrid, Spain, ²⁵Medicine, Universidad Autonoma Madrid, MADRID, Spain, ²⁶Clinic pharmacology, Parc Tauli Hospital Universitari. I3PT. UAB, Sabadell, Spain, ²⁷Hospital de Mérida, Mérida, Spain, ²⁸Hospital Clínico Universitario de Salamanca, Salamanca, Spain, ²⁹Rheumatology, Parc Tauli Hospital Universitari, Sabadell, Barcelona, Spain

Meeting: 2017 ACR/ARHP Annual Meeting

Date of first publication: September 18, 2017

Keywords: Ankylosing spondylitis (AS), Biomarkers, Spondylarthritis, treatment and tumor necrosis factor (TNF)

Session Information

Date: Monday, November 6, 2017

Title: Spondyloarthropathies and Psoriatic Arthritis – Clinical Aspects and Treatment Poster II

Session Type: ACR Poster Session B

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

Background/Purpose:

Some clinical guidance recommends empirical TNFi dose reductions in AS patients despite lack of robust supportive evidence. Recently, we communicated that a strategy of dose reduction in patients with persistent clinical remission is not inferior to full doses. While it has been suggested that drug level monitoring may guide optimization and prevent overtreatment in rheumatoid arthritis patients on TNFi therapy, there is no conclusive data on biomarkers that may help the monitoring of TNFi treatment in AS. The objective of the present study was to explore potential clinical and biologic predictors of poor clinical response, defined as not meeting low disease activity (LDA) defined as: BASDAI, physician global assessment and patient and nocturnal axial pain, all <4, after 1 year of follow-up.

Methods:

This is a nested study on a prospective multicenter, parallel controlled and randomized open-label clinical trial testing non-inferiority of dose reduction vs maintenance of full doses in patients with remission while treated with any antiTNF drug (REDES-TNF, NCT01604629 / EudraCT 2011-005871-18). The study included and analyzed a total of 113 AS patients (55 full dose arm and 58 reduced dose arm) with persistent clinical remission under TNFi.

Clinical variables analyzed incuded ASDAS-CRP, ASAS response criteria, BASDAI, BASFi and quality of life (ASQoL). Blood samples for measurement of TNFi levels, antibodies anti-drug and inflammatory mediators were collected whenever possible within the 24 hours before TNFi Injection. Plasma levels of TNF alpha, IL-6, esclerostin (SOST) and dickkopf-related protein 1 (DKK-1), high sensitivity CRP (hs-CRP). All TNF inhibitor concentrations were measured by capture ELISA with available commercial kits, and antibodies against drugs were analysed by a homemade two-site (bridging) ELISA.

Results: BASFI, ASQoL and the type of TNFi used were all significantly associated with the probability of LDA after 1 year in univariate models, but only the type of TNFi (Infliximab) and BASFI continued to be significant in multivariate models. Since type of TNFi was not randomized, no conclusions can be derived on whether infliximab is having poor outcomes or used differentially. The treatment effect (dose group assigned) did not show significant heterogeneity according to either BASFI (p=0.5244) nor type of TNFi (p=0.887) suggesting that dose reduction is not predictive of poor outcome. Plasma levels for inflammatory biomarkers and drug levels were available for 55 subjects (29 in full dose group and 26 in experimental group); of all of biomarkers analyzed, only values for hs-CRP were higher in subjects not meetign LDA at 1 year. Univariate methods for clinical and analytical biomarkers showed poor predictive value, with lower bonds of 95% CI for ROC AUC values always below 0.62; multivariate methods were unfeasible since no combination of factors improved the univariate models

Conclusion: Baseline BASFI and high hs-CRP serum levels have been identified as potential markers of poor prognosis of LDA at 1 year, regardless of dose reduction or not. Further studies may include these markers and explore additional factors in order to build a predictive model for persistent LDA.

Disclosure: M. Moreno, None; C. Pontes, None; F. Torres, None; A. Sellas-Fernandez, None; M. Almirall, None; J. C. Torre-Alonso, None; T. Clavaguera, None; C. Rodriguez-Lozano, None; L. F. Linares, None; A. Urruticoechea-Arana, None; E. Collantes-Estevez, None; R. Morla, None; D. Reina, None; E. Cuende, None; P. Zarco, None; C. Fernandez-Espartero, None; R. García-Vicuña, None; J. Sanz, None; X. Juanola, None; A. Vallano, None; F. J. Blanco, Pfizer Inc, 5; R. Sanmarti, None; G. Calvo, None; C. Avendaño, None; E. De Miguel, None; R. Vives, None; R. Veroz Gonzalez, None; C. A. Montilla-Morales, None; J. Gratacos-Masmitja, None.

To cite this abstract in AMA style:

Moreno M, Pontes C, Torres F, Sellas-Fernandez A, Almirall M, Torre-Alonso JC, Clavaguera T, Rodriguez-Lozano C, Linares LF, Urruticoechea-Arana A, Collantes-Estevez E, Morla R, Reina D, Cuende E, Zarco P, Fernandez-Espartero C, García-Vicuña R, Sanz J, Juanola X, Vallano A, Blanco FJ, Sanmarti R, Calvo G, Avendaño C, De Miguel E, Vives R, Veroz Gonzalez R, Montilla-Morales CA, Gratacos-Masmitja J. Study of Potential Clinical and Biologic Predictors of Maintaining Good Response at 1 Year Follow-up, in Patients with Ankylosing Spondylitis Under Dose Reduction of TNFi Treatment [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 10). https://acrabstracts.org/abstract/study-of-potential-clinical-and-biologic-predictors-of-maintaining-good-response-at-1-year-follow-up-in-patients-with-ankylosing-spondylitis-under-dose-reduction-of-tnfi-treatment/. Accessed .

« Back to 2017 ACR/ARHP Annual Meeting

ACR Meeting Abstracts - https://acrabstracts.org/abstract/study-of-potential-clinical-and-biologic-predictors-of-maintaining-good-response-at-1-year-follow-up-in-patients-with-ankylosing-spondylitis-under-dose-reduction-of-tnfi-treatment/