321. Long-term treatment effects of tofacitinib in a cohort of therapy resistant Takayasu patients.

Background/ Objectives: Takayasu's arteritis (TAK) is a rare systemic large vessel vasculitis that primarily affects the aorta and its main vessel branches, leading to stenosis or aneurysm. There is no explicit therapy option for therapy-resistant patients that have failed on combination therapy consisting of; glucocorticoid steroids (GS) combined with conventional synthetic disease-modifying anti-rheumatic ugs like methotrexate (MTX), azathioprine (AZA), leflunomide (Lef), tumor necrosis factor inhibitor (TNFi) and tocilizumab (TCZ).

Janus kinase inhibitors (JAKi) seem promising in newly published case reports, in a case series of five patients with refractory TAK in addition to a randomized controlled study of biologic naïve TAK patients treated with JAKi compared to MTX (1, 2).  All these have a short follow-up without imaging outcome.

Methods: TAK patients who failed on multiple combination therapies were included from MEDUB, an "off-label" treatment data registry at Oslo University Hospital.
Patients started with peroral tofacitinib 5 mg bd, combined with ongoing MTX or Lef in addition to GC.  After about 12-24 weeks, tofacitinib was doubled to 10 mg bd if there were insufficient clinical effects. Evaluation of treatment response by; (a) the absence of sympto of vessel inflammation, (b) normalization, or significant reduced C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR), (c) absence of progression in vascular imaging MRI or CTA (d) reduced uptake in ¹⁸F-FDG PET/CT scan using PETVAS scoring (3), and by (e) reduced GC treatment.  Side effects were registered.

Results: The first patient (pt. 1) started with tofacitinib in September 2017. A total of six patients with a mean disease duration of TAK of 6.5 years (0.9-11.5 years) received tofacitinib treatment.  All increased tofacitinib from 5 mg bd to 10 mg bd. The average treatment time with tofacitinib is currently 2.7 years (1.1 - 4.0 years), with a total of 16 patients years of tofacitinib treatment.  Five patients (5/6 =83%) had a clinical response. In the five patients with clinical response, there was significantly reduced CRP from a mean of 67.6 mg/L to 3.5 mg/L and ESR from 56.4 mm/h to 10 mm/h, respectively. There was no radiographic progression, and a mean PETVAS score fell from a mean value of 15 (range 21-10) to 9.4 (range 15-5) with a mean fall in PETVAS score of 5.6 (range 11-3). The mean dose of GC was reduced from 15.8 to 7.7 mg/daily.  There were no severe adverse events registered.  All the patients with coexisting autoimmune disease (pt. 1, 2, and 4) responded in their related sympto

Two patients paused the treatment (non-ug-related) and developed severe flare shortly after but went in remission after a restart of tofacitinib. 

Conclusions: Tofacitinib was well tolerated and had long-term clinical and steroid-sparing effects in most therapy-resistant TAK patients combined with GC and MTX or Lef. Long-term randomized controlled studies of JAKi in TAK patients are warranted.

Disclosures: None.