POS0917 EFFECTIVENESS AND SAFETY OF COMBINED BIOLOGICAL THERAPY IN PATIENTS WITH REFRACTORY SPONDYLOARTHRITIS
Authors: C. Valero, J. P. Baldivieso, I. Llorente, E. Tomero Muriel, I. González-Álvaro, S. Castañeda, R. Garcia de Vicuna
Journal: Annals of the Rheumatic Diseases (2021)

Background: Biological therapy in combination is discouraged in the guidelines for the treatment of immune-mediated inflammatory diseases, attending to safety reasons. However, combined biological therapy could be a valid alternative in patients with highly refractory spondyloarthritis (SpA) as has been previously demonstrated in some reluctant inflammatory bowel disease patients. Published experiences in the literature are very scarce and the follow-up is limited. Objectives: The aim of this study is to determine the effectiveness and safety of the association of biological drugs in patients with SpA and describe the clinical profile of these patients. Methods: This is a retrospective, cross-sectional and descriptive study. We included patients with SpA who had received simultaneously at least two biological drugs with different therapeutic targets. We reviewed the database of our hospital that included all patients diagnosed with SpA meeting the ASAS criteria for axial SpA under active biological treatment. Demographics, clinical and laboratory data, previous treatments, disease activity index (ASDAS CRP) and adverse events were collected. Remission and low activity criteria were considered according to cut-off descriptions in ASDAS CRP, &lt;1.3 and 2.1, respectively. Results: We identified six patients with SpA receiving combined biological therapy (Table 1). All patients showed high disease activity at the start of combination treatment and most of them presented several disease domains involvement. The average of previous biologics drugs was 5.33 ± 1.75. Four patients received an anti-TNF in combination with an anti-IL17 agent and one patient with concomitant Crohn disease was prescribed an anti-TNF combined with an anti-IL23 agent. The sixth patient, with SpA and concomitant systemic lupus erythematosus, received rituximab with an anti-IL17 (Table 1). The median treatment duration of the combined biological therapy was 12.5 months (IQR 4-43.5; range: 4-117). All patients achieved low disease activity or clinical remission at some point during follow-up, allowing for initial de-escalation of initial dose in some patients. Only one patient experienced a transient relapse (unic uveitis episode). No relevant adverse effects have been found clearly attributable to combination therapy. A 60-year-old patient with multiple comorbidities has stopped treatment due to aggravation of a previous liver cirrhosis. Conclusion: Combined biological therapy could be an effective therapeutic alternative to patients with multidomain and refractory SpA. In our series, we provide acceptable safety data for follow-up periods that it are longer than the majority of reported cases to date. Table 1. Main characteristics of patients with SpA and treatment schedules. Characteristics Patients (N= 6) Male, n 3 Age at diagnosis (years) mean (IQR) 25 (8-52) Ethnicity, n 5 Caucasian; 1 Hispanic Smoker, n 1 Diagnosis 3 Juvenile SpA-ERA, 2 PsA, 1 SpA + SLE Duration of disease (years) mean (IQR) 20.5 (5.25-33.5) Domains involved, n 6 Axial 6 Peripheral 6 Enthesis 5 Extra-articular 2 psoriasis (1 with aortic insufficiency), 2 uveitis, 1 Crohn disease HLA-B27 +, n 4 Previous biological or targeted therapy, n Anti-TNF 6 (5 etanercept, 5 adalimumab, 4 infliximab, 4 golimumab, 3 certolizumab) Anti-IL17 6 (5 secukinumab, 1 ixekizumab) Jakinibs 1 (1 tofacitinib) Other 3 (1 anakinra, 1 tocilizumab, 1 apremilast) Combined biological Therapy Treatment 1 + Treatment 2 Time of follow-up (months) Actual state 1.GOL 100 mg/4w + SEC 150 mg/1w 117 Remission 2.ETN 50 mg/1w + SEC 150 mg/2w 9 *Low activity 3.ETN 50 mg/1w + SEC 150 mg/4w; 16 Remission 4.GOL 100 mg/4w + SEC 150 mg/2w 4 Low activity 5.GOL 100 mg/3w + RIS 250 mg/12w 4 Low activity 6.RTX 2g infusion + SEC 150 mg/4w 19 Remission *At treatment interruption Abbreviations: ERA: enthesitis-related arthritis; ETN: etanercept; GOL: golimumab; IQR: interquartile range; PsA: psoriatic arthritis; RIS: risankizumab; RTX: rituximab SEC: secukinumab; SLE: systemic lupus erythematosus; SpA: spondyloarthritis; w: week. Disclosure of Interests: None declared