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

Tocilizumab Infusion RoAcemtra (EU) or Actemra (Rest of the world)

Familial Mediterranean Fever

Experimental arm's patients will obtain TCZ intravenously once every 4 weeks for 28 weeks

Tocilizumab Infusion RoAcemtra (EU)

Experimental arm's patients will obtain saline intravenously once every 4 weeks for 16 weeks. If necessary, patients will get "rescue medication" after week 16 to week 28.

0.9% physiological saline

Universitätsklinikum Köln, Klinik I für Innere Medizin

Charité Universitätsmedizin Berlin, Klinik für Rheumatologie und Klinische Immunologie, Abteilung -Neue Therapien & Studien

University Hospital Tuebingen; Department of oncology, hematology, rheumatology, immunology and pulmology

Tocilizumab for the Treatment of Familial Mediterranean Fever

Tocilizumab for the Treatment of Familial Mediterranean Fever - A Randomized, Doubleblind, Phase II Proof of Concept Study

Efficacy: measured by Physician's Global Assessment of disease activity (PGA) will be assessed at every visit
The PGA will be based on a 5 point-scale (from 0 to 4):
0=none (no) disease associated clinical signs and symptoms*
minimal disease associated clinical signs and symptoms*
mild disease associated clinical signs and symptoms*
moderate disease associated clinical signs and symptoms*
severe disease associated clinical signs and symptoms* *sign and symptoms for evaluation of PGA: chest pain, abdominal pain, arthralgia, arthritis, skin rash, fever (body temperature ≥ 38.0°C). Patient are asked to fill out a patient's diary to help the physician to judge the PGA primary endpoint will be the number of patients achieving an adequate response to treatment at week 16, defined as: PGA ≤ 2 + normalized ESR or CRP (the one that led to inclusion must be normalized) + normalized SAA

To evaluate the safety of TCZ in subjects with FMF Safety of participating subjects will be assessed by regular clinical examinations, laboratory tests and reporting of adverse events. In case of a relapse the physician will discuss further treatment options with the patient and will initiate further treatment (according to local standard). Clinical laboratory testing for all study-relevant evaluations will be performed at all visits.
Laboratory testing has to include:
• ESR [mm after 1hour]

To evaluate the proportion of patients with the serological remission at week 16 + 28 (defined as CRP < 0.5 mg/dl)

To evaluate the proportion of patients with normalized SAA level at week 16 + 28 (defined as SAA < 10mg/l)

Safety of TCZ in subjects with FMF Safety of participating subjects will be assessed by regular clinical examinations, laboratory tests and reporting of adverse events. In case of a relapse the physician will discuss further treatment options with the patient and will initiate further treatment (according to local standard).
CRP [mg/L]

Safety of TCZ in subjects with FMF Safety of participating subjects will be assessed by regular clinical examinations, laboratory tests and reporting of adverse events. In case of a relapse the physician will discuss further treatment options with the patient and will initiate further treatment (according to local standard).
complete blood cell count with differential [cells/µl]

to evaluate the safety of TCZ in subjects with FMF Safety of participating subjects will be assessed by regular clinical examinations, laboratory tests and reporting of adverse events. In case of a relapse the physician will discuss further treatment options with the patient and will initiate further treatment (according to local standard).
serum chemistry function tests :
Creatinine [mg/dl]

to evaluate the safety of TCZ in subjects with FMF Safety of participating subjects will be assessed by regular clinical examinations, laboratory tests and reporting of adverse events. In case of a relapse the physician will discuss further treatment options with the patient and will initiate further treatment (according to local standard).
renal function tests :
Uric Acid [mg/dl]

to evaluate the safety of TCZ in subjects with FMF Safety of participating subjects will be assessed by regular clinical examinations, laboratory tests and reporting of adverse events. In case of a relapse the physician will discuss further treatment options with the patient and will initiate further treatment (according to local standard).
renal function tests :
GFR [ml/min]

Safety of TCZ in subjects with FMF Safety of participating subjects will be assessed by regular clinical examinations, laboratory tests and reporting of adverse events. In case of a relapse the physician will discuss further treatment options with the patient and will initiate further treatment (according to local standard).
GGT[IU/L]

Safety of TCZ in subjects with FMF Safety of participating subjects will be assessed by regular clinical examinations, laboratory tests and reporting of adverse events. In case of a relapse the physician will discuss further treatment options with the patient and will initiate further treatment (according to local standard).
ALT [IU/L]

Safety of TCZ in subjects with FMF Safety of participating subjects will be assessed by regular clinical examinations, laboratory tests and reporting of adverse events. In case of a relapse the physician will discuss further treatment options with the patient and will initiate further treatment (according to local standard).
AST[IU/L]

to evaluate the safety of TCZ in subjects with FMF Safety of participating subjects will be assessed by regular clinical examinations, laboratory tests and reporting of adverse events. In case of a relapse the physician will discuss further treatment options with the patient and will initiate further treatment (according to local standard).
Bilirubin [mg/dl]

University Hospital Tuebingen

Multi-center, phase II, randomized, placebo-controlled, double blind proof of concept trial

Investigator and patient will be masked. There' ll be one qualified person in each center who s not going to be masked to prepare study treatment

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

Takayasu's Arteritis

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

Mayo Clinic

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

giant cell arteritis/lafyèv

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

Tocilizumab for the Treatment of Familial Mediterranean Fever

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

Determining Disease Activity Biomarkers in Individuals With Giant Cell Arteritis

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