Giant Cell Arteritis

Prednisone treatment

Tocilizumab 162 mg/week subcutaneous from W0 to W51 (52 injections)

Tocilizumab treatment

Methotrexate subcutaneous from W0 to W51 (52 administrations).
W0: 7.5 mg/week
W1: 0.2 mg/Kg/week
W2 to W51: 0.3 mg/Kg/week (without exceeding 20 mg/week) Folic acid 10 mg/week, 48h after taking Methotrexate, from W0 to W51

Methotrexate treatment

Questionnaires

Additionnal blood samples for immunomonitoring

Blood samples

CHU de Dijon

MEthotrexate Versus TOcilizumab for Treatment of GIant Cell Arteritis: a Multicenter, Randomized, Controlled Trial

Centre Hospitalier Universitaire Dijon

Takayasu's Arteritis

Exercise

University of Sao Paulo

Exercise in Juvenile Takayasu Disease

Exercise in Juvenile Takayasu Disease: a Randomized Controlled Trial

as assessed by positron emission tomography - magnetic ressonance (PET-MR)

interleukin-6, interleukin 10, interleukin-12

as assessed by maximal cardiopulmonary test

Lean, fat and bone mass, as assessed by dual energy x-ray absorptiometry

The test is performed by measuring the time to stand up and down for 30 seconds. The patient should make two attempts and the best performance will be considered for the analyzes.

The "Timed Up-And-Go" test, which evaluates the time it takes for the patient to get up from a chair, walk three meters, make a 180-degree turn, and return to the chair. The patient should perform two attempts and the best performance will be considered for the analyzes.

will be performed by the maximum repetition test, where the objective is to find a maximal repetition for lower limbs by leg press exercise 45º and for upper limbs by bench press exercise

The final PVAS is a clinical index of 64 manifestations of active vasculitis, divided into five domains: general, cutaneous, cardiovascular, abdominal and renal.

The NIH criteria is an instrument that will evalueted the disease specific symptoms and his activity. Active disease will arbitrarily defined as new onset or worsening of at least 2 of the following 4 features: (I) signs and symptoms of vascular ischemia or inflammation (e.g. claudication, decreased or absent extremity pulses or blood pressure, bruits, or carotidynia); (2) elevated erythrocyte sedimentation rate; (3) angiographic abnormalities; and (4) systemic symptoms not attributable to another disease.

ITAS2010 contains 44 items with 33 features arising from the cardiovascular system. Seven key items are weighted to score 2 and all others score 1 only.

The Childhood Health Assessment Questionnaire (CHAQ) is a disease specific health instrument that measures functional ability in daily living activities in children

The level of physical activity of patients will be measured using the Actigraph GT3x® triaxial accelerometer (Actigraph®).

The Fatigue severity scale will be used to monitor the change in fatigue in response to the intervention. For each item, you must tick from 1 totally disagree to 7 agree totally. The total number of points may vary from 9 to 63, and it is established that values equal to or greater than 28 are indicative of the presence of fatigue

after maximal aerobic capacity, the blood pressure will be will be measured in the four limbs, both arms and legs, every fifteen minutes, for an hour.

Bruno Gualano

Professor

Federal University of São Paulo

Takayasu Arteritis

Boston University School of Medicine

Mayo Clinic

Cleveland Clinic Foundation

St. Joseph's Healthcare

Mount Sinai Hospital, Toronto

Use of MRI and PET for Assessing Disease Activity in Takayasu's Arteritis

VCRC Imaging Protocol for Magnetic Resonance and Positron Emission Tomography in Large-vessel Vasculitis (Takayasu's Arteritis):Development as Clinical Trial Outcome Measures

Peter Merkel

Office of Rare Diseases (ORD)

National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

Rare Diseases Clinical Research Network

This is a randomized withdrawal design protocol. All participants will receive abatacept and prednisone (a glucocorticoid) for the first 3 months. Abatacept will be given intravenously on selected days. Prednisone will be started at a dose of 40 to 60mg, then tapered to 20mg by Month 3, and finally further tapered until discontinuation is reached. At Month 3, participants who have achieved remission will be randomly assigned under double-blind conditions to receive monthly infusions of either abatacept or placebo. Participants who are assigned to abatacept at this point will be in Group A for giant cell arteritis and Group C for Takayasu arteritis.

This is a randomized withdrawal design protocol. All participants will receive abatacept and prednisone (a glucocorticoid) for the first 3 months. Abatacept will be given intravenously on selected days. Prednisone will be started at a dose of 40 to 60mg, then tapered to 20mg by Month 3, and finally further tapered until discontinuation is reached. At Month 3, participants who have achieved remission will be randomly assigned under double-blind conditions to receive monthly infusions of either abatacept or placebo. Participants who are assigned to placebo at this point will be in Group B for giant cell arteritis and Group D for Takayasu arteritis.

This is a randomized withdrawal design protocol. All participants with giant cell arteritis will receive prednisone (a glucocorticoid) and abatacept for the first 12 weeks. Prednisone will be started at a dose of 40 to 60mg, then tapered to 20mg by Week 12 and finally further tapered until discontinuation is reached at Week 28. Abatacept will be given intravenously on Day 1, Day 15, and Week 8 at a fixed dose approximating 10mg per kilogram of body weight. The following dosing rules for abatacept will be followed:
Participants weighing less than 60kg will receive 500mg of abatacept.
Participants weighing 60 to 100kg will receive 750mg of abatacept.
Participants weighing more than 100kg will receive 1000mg of abatacept.
At Week 12, participants who have achieved remission will be randomly assigned under double-blind conditions to receive monthly infusions of either abatacept or placebo. Participants who are assigned to abatacept at this point will be in Group A.

Group A - Abatacept in Giant Cell Arteritis

This is a randomized withdrawal design protocol. All participants with giant cell arteritis will receive prednisone (a glucocorticoid) and abatacept for the first 12 weeks. Prednisone will be started at a dose of 40 to 60mg, then tapered to 20mg by Week 12 and finally further tapered until discontinuation is reached at Week 28. Abatacept will be given intravenously on Day 1, Day 15, and Week 8 at a fixed dose approximating 10mg per kilogram of body weight. The following dosing rules for abatacept will be followed:
Participants weighing less than 60kg will receive 500mg of abatacept.
Participants weighing 60 to 100kg will receive 750mg of abatacept.
Participants weighing more than 100kg will receive 1000mg of abatacept.
At Week 12, participants who have achieved remission will be randomly assigned under double-blind conditions to receive monthly infusions of either abatacept or placebo. Participants who are assigned to placebo at this point will be in Group B.

Group B - Placebo in Giant Cell Arteritis

This is a randomized withdrawal design protocol. All participants with Takayasu arteritis will receive prednisone (a glucocorticoid) and abatacept for the first 12 weeks. Prednisone will be started at a dose of 40 to 60mg, then tapered to 20mg by Week 12 and finally further tapered until discontinuation is reached at Week 28. Abatacept will be given intravenously on Day 1, Day 15, and Week 8 at a fixed dose approximating 10mg per kilogram of body weight. The following dosing rules for abatacept will be followed:
Participants weighing less than 60kg will receive 500mg of abatacept.
Participants weighing 60 to 100kg will receive 750mg of abatacept.
Participants weighing more than 100kg will receive 1000mg of abatacept.
At Week 12, participants who have achieved remission will be randomly assigned under double-blind conditions to receive monthly infusions of either abatacept or placebo. Participants who are assigned to abatacept at this point will be in Group C.

Group C - Abatacept in Takayasu Arteritis

This is a randomized withdrawal design protocol. All participants with Takayasu arteritis will receive prednisone (a glucocorticoid) and abatacept for the first 12 weeks. Prednisone will be started at a dose of 40 to 60mg, then tapered to 20mg by Week 12 and finally further tapered until discontinuation is reached at Week 28. Abatacept will be given intravenously on Day 1, Day 15, and Week 8 at a fixed dose approximating 10mg per kilogram of body weight. The following dosing rules for abatacept will be followed:
Participants weighing less than 60kg will receive 500mg of abatacept.
Participants weighing 60 to 100kg will receive 750mg of abatacept.
Participants weighing more than 100kg will receive 1000mg of abatacept.
At Week 12, participants who have achieved remission will be randomly assigned under double-blind conditions to receive monthly infusions of either abatacept or placebo. Participants who are assigned to placebo at this point will be in Group D.

Group D - Placebo in Takayasu Arteritis

Total

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Region of Enrollment

Relapse: presence of active disease occurring after a period of remission
Remission: absence of active disease
Active disease defined by clinical features or imaging or both:
Clinical features:
1 or more of the following attributed to GCA/TAK:
Sustained fever of >38 C for > 1 week
Vascular pain/tenderness > 1 day, non-fleeting
Headache a) present > 1 day b) non-fleeting c) not relieved with analgesics d) not typical for pre-existing headaches
Ischemic retinopathy, optic neuropathy, or visual loss
Tongue/jaw pain and/or claudication
TIA or stroke
Extremity claudication
Musculoskeletal symptoms + ESR of > 40 mm/hr or CRP above the normal limit
Malaise/fatigue + ESR of > 40 mm/hr or CRP above the normal limit
Other symptoms/signs due to GCA/TAK requiring reinstitution/increase in GC
Imaging features
• Development of new vascular stenosis or aneurysm in new vascular territories as seen by MRI/MRA or arteriogram

This is a randomized withdrawal design protocol. Participants with giant cell arteritis will receive prednisone (a glucocorticoid) and abatacept for the first 12 weeks. Prednisone will be started at a dose of 40 to 60mg, then tapered to 20mg by Week 12 and finally further tapered until discontinuation is reached at Week 28. Abatacept will be given intravenously on Day 1, Day 15, and Week 8 at a fixed dose approximating 10mg per kilogram of body weight. The following dosing rules for abatacept will be followed:
Participants weighing less than 60kg will receive 500mg of abatacept.
Participants weighing 60 to 100kg will receive 750mg of abatacept.
Participants weighing more than 100kg will receive 1000mg of abatacept.
At Week 12, participants who have achieved remission will be randomly assigned under double-blind conditions to receive monthly infusions of either abatacept or placebo. Participants who are assigned to abatacept at this point will be in Group A.

This is a randomized withdrawal design protocol. Participants with Takayasu arteritis will receive prednisone (a glucocorticoid) and abatacept for the first 12 weeks. Prednisone will be started at a dose of 40 to 60mg, then tapered to 20mg by Week 12 and finally further tapered until discontinuation is reached at Week 28. Abatacept will be given intravenously on Day 1, Day 15, and Week 8 at a fixed dose approximating 10mg per kilogram of body weight. The following dosing rules for abatacept will be followed:
Participants weighing less than 60kg will receive 500mg of abatacept.
Participants weighing 60 to 100kg will receive 750mg of abatacept.
Participants weighing more than 100kg will receive 1000mg of abatacept.
At Week 12, participants who have achieved remission will be randomly assigned under double-blind conditions to receive monthly infusions of either abatacept or placebo. Participants who are assigned to abatacept at this point will be in Group C.

This is a randomized withdrawal design protocol. Participants with Takayasu arteritis will receive prednisone (a glucocorticoid) and abatacept for the first 12 weeks. Prednisone will be started at a dose of 40 to 60mg, then tapered to 20mg by Week 12 and finally further tapered until discontinuation is reached at Week 28. Abatacept will be given intravenously on Day 1, Day 15, and Week 8 at a fixed dose approximating 10mg per kilogram of body weight. The following dosing rules for abatacept will be followed:
Participants weighing less than 60kg will receive 500mg of abatacept.
Participants weighing 60 to 100kg will receive 750mg of abatacept.
Participants weighing more than 100kg will receive 1000mg of abatacept.
At Week 12, participants who have achieved remission will be randomly assigned under double-blind conditions to receive monthly infusions of either abatacept or placebo. Participants who are assigned to placebo at this point will be in Group D.

Primary Outcome - Relapse-free Survival (RFS)

Study Entry to Week 12

After Week 12 (Randomized Study Period)

Carol A Langford, MD MHS

Participants will receive a fixed dose of abatacept, approximating 10mg per kilogram of body weight. The following dosing rules will be followed:
Participants weighing less than 60kg will receive 500mg of abatacept.
Participants weighing 60 to 100kg will receive 750mg of abatacept.
Participants weighing more than 100kg will receive 1000mg of abatacept.
Abatacept will be administered in a 30-minute intravenous infusion on Days 1, 15, 29 (Month 1) and at Month 2. In the absence of toxicity or relapse, participants will remain on abatacept at the same dosage until randomization at Month 3. After randomization, only Group A (giant cell arteritis) and Group C (Takayasu arteritis) participants will continue on abatacept.

Abatacept

Placebo abatacept infusions will be given monthly after random assignment at Month 3.

Placebo

Click here for the Cleveland Clinic Center for Vasculitis Care and Research Web site

Cedars-Sinai Medical Center

Johns Hopkins Medical Center

Boston University

Hospital for Special Surgery

Cleveland Clinic

University of Pittsburgh

University of Utah

St. Joseph's Hospital

Mt. Sinai Hospital Toronto

Abatacept for Treating Adults With Giant Cell Arteritis and Takayasu's Arteritis

Concurrent Pilot Studies in Giant Cell Arteritis and Takayasu's Arteritis to Examine the Safety, Efficacy, and Immunologic Effects of Abatacept (CTLA4-Ig) in Large Vessel Vasculitis

arteritis/fatigue

MEthotrexate Versus TOcilizumab for Treatment of GIant Cell Arteritis: a Multicenter, Randomized, Controlled Trial

Exercise in Juvenile Takayasu Disease

Use of MRI and PET for Assessing Disease Activity in Takayasu's Arteritis

Abatacept for Treating Adults With Giant Cell Arteritis and Takayasu's Arteritis

Vispilnīgākā ārstniecības augu datu bāze, kuru atbalsta zinātne