340. The effect of upfront methotrexate and 2nd line infliximab on vascular accrual in Takayasu vasculitis

Background/objectives: Takayasu vasculitis is a vasculitis affecting the aorta, its primary branches and less often the coronary and pulmonary arteries(1). The disease course is most often remitting/relapsing or chronic active but some go into longstanding remission on treatment (2, 3). This has led to that the newly published ACR and EULAR guidelines now recommend an upfront treatment with DMARD followed by TNF or IL-6 inhibitors in resistant cases(4, 5). To our knowledge there is no study that has specifically studied the effect of upfront use of traditional DMARDs or TNF inhibitors as second line treatment focusing on accumulation of vascular damage during follow up, which was the aim of this study. Methods: Patients were retrieved from a population based cohort database in the South-East Norway(1). Data variables were retrieved from medical chart, laboratory and imaging results (1). All the patients fulfilled either the ACR classification criteria (6) and/or the modified Ishikawa diagnostic criteria for TAK (7). Patients who were immediately started on methotrexate at diagnoses and patients started on infliximab after one DMARD failure were identified. Patients with at least yearly follow up imaging were included. Number of vascular lesions (narrowing/stenosis/occlusion/aneurysm) reported in imaging results at the time of treatment start and during follow up were registrated. Results: The mean age at disease onset in the total cohort was 30.4 (SD 14) and 33.9 (SD 15) at diagnoses. Follow up time was 11.7 years (SD 11.9). Eighty-six (89%) were female and 19 patients were originated from Asia or Africa (19%). The patients had median 10 visits at our clinic (Oslo University Hospital). During the follow up time 392 and 108 CT angiography, 245 ultrasounds of neck arteries and 198 PET-CT were taken. Twenty-three patients received Methotrexate (MTXi) immediately at time of diagnoses. They were mean 30.6 (SD 13.9) years old. Seventy-nine percentages were female and 83 % were European Caucasian. The diagnostic delay was mean 16 months (SD 23.4). Seventy percentages had ≤12 month’s delay in the diagnoses. The median start dose was 15 mg weekly (range 10-20 mg) and 20 mg at last visit (range 10-20mg). All patients started with parallel Prednisolone therapy, mean 50 mg (range 30-60 mg). The mean treatment duration was 27.6 months (SD 17.5 mts) with total 52 patient years on treatment. At the time of MTXi start the patients had total 44 lesions, or mean 1.9 (SD 1.9, range 0-6). Twenty-seven patients were started on infliximab (INF) after one DMARD failure. The patients were mean 31.1 (SD 12.7) age old at treatment start, all female and 81% were European Caucasian. A mean 36.2 months (SD 41) went from diagnoses to start of INF treatment. At the start of INF treatment 26 (96.3%) were on Prednisolone and 25 (92.6%) on DMARDs (23 MTX and 2 AZA). Seventeen of 25 patients (not available in 2) had developed new lesions before INF start. Treatment duration was mean 42.4 months (SD 32.6) with total 92 patient years of observation. The start dose was 3 mg/kg in 18 patients and 5 mg/kg in 7 patients every 8th week. Nineteen of 25 (76%) had to increase the initial dose during the treatment time. Maximum dose was 10 mg/kg every 4th week (2 patients). Eighty-eight and 69% were still on Prednisolone and DMARDs in last visit. The patients had 105 lesions when treatment was started or mean 4.6 (SD 2.9, range 0-12). During the follow up two patients treated with infliximab (7.4%) developed a total of 2 new vascular lesion compared to 7 patients (30.4%), with total 15 new lesions in the MTXi patients (chi square p=0.04, odd ratio 0.18 (CI 0.03-0.99) (fig 1). The infliximab patients had 2.2 new lesions per 100 patient years compared to 28.8 per 100 patients years in upfront MTX (p