339. The effect of upfront methotrexate and 2nd line infliximab on disase activity in Takayasu vasculitis
Creators: name: Gudbrandsson1, Birgir
Publisher: name: Zenodo
Year: 2022
Subjects: Vasculitis
ANCA
Abstracts
Giant Cell Arthritis
MPA
GPA
EGPA
Takayasu
IgA vasculitis

description: <strong>Background/objectives</strong>: Takayasu vasculitis (TAK) 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). It is known that a large majority of patients with continuous active disease do develop new vascular lesions and have a worse outcome (4, 5). The newly published ACR and EULAR guidelines now recommend an upfront treatment with DMARD followed by TNF or IL-6 inhibitors in resistant cases(6, 7). 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 on disease activity in TAK, which was the aim of this study. <strong>Methods: </strong>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 (8) and/or the modified Ishikawa diagnostic criteria for TAK (9). Patients who were immediately started on methotrexate at diagnoses and patients started on infliximab after one DMARD failure were identified. Only patients with at least to follow up visits and imaging were included. Disease activity was assessed using the definition coming from a previous National Institute of Health (NIH) study, which define the clinical status on the basis of 4 elements: 1) systemic features (no other cause identified), 2) elevated erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP), 3) features of vascular ischemia or inflammation (such as limb claudication, diminished or absent pulse, bruit, pain over large vessels, asymmetric blood pressure), and 4) new vascular lesion(s) on imaging studies i.e. new stenosis or new dilatation (not previously diagnosed). The active phase was defined as new onset or worsening of 2 or more of these features. A new lesion in a previously unaffected artery was interpreted as clear sign of active disease. Disease remission was defined as resolution of clinical and laboratory features of active disease and the absence of new vascular lesions on sequential imaging studies. Sustained remission was defined in those who met these conditions for at least six months while on a treatment regimen including prednisone &lt;10 mg/day. Continuous data are presented as mean with standard deviation or range and categorical data are presented as numbers (percent). The means were compared by independent t-test and the proportions were compared by Chi-square test or Fisher exact as appropriate. The p value of &lt;0.05 was considered significant. <strong>Results: </strong>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 diagnoses the patients had a mean 95 in CRP (SD 88) and 75 in ESR (SD 35). At last visit the CRP had fell to mean 8.7 (p&lt;0.001) and ESR to 19 (p&lt;0.001). At last visit the mean prednisolone dose was 7.5 mg (SD 4). Nine patients were still taking 10 mg or more prednisolone (39%) and only two were off (8.7%). 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). 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 8<sup>th</sup> week. Nineteen of 25 (76%) had to increase the initial dose during the treatment time. Maximum dose was 10 mg/kg every 4<sup>th</sup> week (2 patients). At start of treatment the mean CRP and ESR was 22 (SD 19) and 30 (SD 14) respectively. At las visit the mean CRP had fell to 7 (SD 12) (p=0.007) and ESR to 18 (SD 15) (p=0.001). Eighty-eight and 69% were still on Prednisolone and DMARDs at last visit. At the start of treatment the mean prednisolone dose was 13.5 mg (SD 8) compared to 8 (SD 8) at last visit (p=0.02). In fig 1 one can see the comparison of remission rate and NIH score between MTXi and 2<sup>nd</sup> line infliximab during follow up. <strong>Conclusions:</strong> In conclusion this retrospective population based observational study provides a novel data on the effectiveness of upfront methotrexate and Infliximab as 2<sup>nd</sup> line treatment on disease activity during follow up in real life setting. Significantly more patients on infliximab obtained remission and sustained remission during follow up than patients in the MTXi arm. Based on these results we clinician should probably have a lower threshold to start with infliximab earlier/early in the disease course in TAK patients who do not obtain remission. <strong>Disclosures: </strong>none