AB0361 EFFECTIVENESS AND SAFETY OF INFLIXIMAB DOSE ESCALATION IN PATIENTS WITH REFRACTORY TAKAYASU ARTERITIS: A REAL-LIFE EXPERIENCE FROM A MONOCENTRIC COHORT
Authors: A. Tomelleri, C. Campochiaro, S. Sartorelli, F. Baldassi, F. Fallanca, M. Picchio, E. Baldissera, L. Dagna
Journal: Annals of the Rheumatic Diseases (2021)

Background: Most published evidence on infliximab (IFX) in Takayasu arteritis (TAK) refers to its use at the standard dose of 5 mg/kg every 6-8 weeks 1 . However, in other diseases such as rheumatoid arthritis or Crohn’s disease 2,3 , it has been already demonstrated that IFX often requires a dose escalation to maintain its response. Objectives: To evaluate effectiveness and safety of IFX dose escalation in TAK patients. To identify predictors of refractoriness to standard-dose IFX. Methods: Medical records of IFX-treated TAK patients from a large single-centre observational cohort were reviewed. Decisions on IFX start, interruption, and dose modification were always made by the same experienced physician (EB). IFX therapy duration and reasons for dose escalation and therapy suspension were evaluated. Occurrence of adverse events was recorded. A comparison between patients who maintained IFX standard-dose and those who needed dose-escalation was performed. Factors predicting standard-dose refractoriness were analyzed. Results: Forty-one patients were included (38 women; median age at IFX start, 36 [IQR, 28-45] years; median disease duration, 22 [13-60] months). Starting IFX dose was 5 mg/kg 6-weekly; 39 patients (95%) were on concomitant csDMARD and 38 patients (93%) on systemic glucocorticoids (GC). IFX dose escalation was performed in the majority of patients (n=28, 68%) (Figure 1). Persistence/recurrence of clinical symptoms was the most frequent reason for dose escalation (62%). Median IFX therapy duration was 39 (26-61) months in the standard-dose and 68 (38-87) months in the intensified-dose group. Patients in the intensified-dose group had a higher number of relapses (3.4 vs 0.8 events/patient), expression of a more aggressive disease phenotype. Nevertheless, in only 8 patients (29%) from this group IFX was suspended, after a median of 38 (31-71) months. Causes of suspension were loss of response (n=7) or patient’s request (n=1). GC were successfully suspended in 4 patients from the standard-dose (36%) and 3 patients from intensified-dose (11%) group. Median daily prednisone dose was reduced from 10 (6-10) to 3 (0-5) mg in the standard-dose group, and from 13 (9-18) to 5 (4-5) mg in the intensified-dose group. Three patients from the intensified-dose group had a serious infection; one patient from the standard-dose group developed paradoxical psoriasis. At univariate analysis, younger age at diagnosis and at IFX start were associated with IFX escalation (Table 1). Table 1. Factors influencing IFX dose escalation in patients with TAK (Cox proportional hazards model) Standard-dose IFX Intensified-dose IFX P -value Age at diagnosis, years 40 (34-46) 30 (23-40) 0.031 Diagnostic delay, months 12 (7-77) 27 (15-50) 0.73 Age at IFX start, years 42 (38-61) 34 (27-44) 0.040 Delay before IFX start, months 33 (14-90) 24 (11-53) 0.48 Daily PDN at IFX start, mg 8.75 (5-10) 11.25 (8.5-16.25) 0.051 CRP at IFX start, mg/L 6.5 (2.1-9.3) 10.7 (5.2-20.9) 0.07 Class V Numano, n (% ) 3 (30) 16 (57) 0.133 PETVAS score 8 (6-12) 12 (9-16) 0.056 Figure 1. Infliximab dose escalation regimens (the cross (x) indicates treatment suspension) Conclusion: In TAK, dose escalation can be a safe strategy to optimize IFX durability in refractory patients. Younger patients seem to be more refractory to standard dosages. References: [1]Mekinian A, Néel A, Sibilia J, et al. Efficacy and tolerance of infliximab in refractory Takayasu arteritis: French multicentre study. Rheumatology. 2012; 51:882–6 [2]Ollendorf DA, Massarotti E, Birbara C, et al. Frequency, predictors, and economic impact of upward dose adjustment of infliximab in managed care patients with rheumatoid arthritis. J Manag Care Pharm. 2005;11(5):383-93 [3]Taxonera C, Olivares D, Mendoza JL, et al. Need for infliximab dose intensification in Crohn’s disease and ulcerative colitis. World J Gastroenterol. 2014;20(27):9170-7 Disclosure of Interests: Alessandro Tomelleri: None declared, Corrado Campochiaro: None declared, Silvia Sartorelli: None declared, Francesco Baldassi: None declared, Federico Fallanca: None declared, Maria Picchio: None declared, Elena Baldissera Speakers bureau: Pfizer, Roche, Sanofi-Genzyme, Consultant of: Novartis, Lorenzo Dagna Consultant of: Abbvie, Amgen, Biogen, Bristol-Myers Squibb, Celltrion, Galapagos, GlaxoSmithKline, Novartis, Pfizer, Roche, Sanofi-Genzyme, and SOBI., Grant/research support from: The Unit of Immunology, Rheumatology, Allergy and Rare Diseases (UnIRAR) received unresctricted research/educational grants from Abbvie, Bristol-Myers Squibb, Celgene, GlaxoSmithKline,Janssen, Merk Sharp &amp; Dohme, Mundipharma Pharmaceuticals, Novartis, Pfizer, Roche, Sanofi Genzyme, and SOBI