Institutional Review Board, Hospital for Special Surgery
December 13, 2013
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Jessica Gordon, MD
Lindsay Lally, MD
Mary K. Crow, MD
Uzunma Udeh, BA
Daniele Lerner, BA
Nina Paddu, BA
Steven Benkert, R.Ph
We will enroll a total of 10 patients for an open label 15-month single center study at the Hospital for Special Surgery. Patients must be enrolled within one month of diagnosis of polymyalgia rheumatica. Patients must have been treated with no more than 30mg of prednisone or its equivalent since their diagnosis, and if treated with 30mg of prednisone or its equivalent, this must have been for no more than 2 weeks. Additionally, patients must be on less than or equal to 20mg of prednisone daily or its equivalent at enrollment to be eligible. They must not have giant cell arteritis, rheumatoid arthritis, other connective tissue diseases or a contra-indication to the use of Tocilizumab. The primary hypothesis being tested is that Tocilizumab will have an acceptable safety and tolerability profile in patients with polymyalgia rheumatica, and that treatment with Tocilizumab will result in protocol-defined Disease Remission (DR), without relapse or recurrence at 6 months from trial entry, while remaining off corticosteroids. Disease Remission (DR) will be defined as the disappearance of signs and symptoms of polymyalgia rheumatica (aching and stiffness of the shoulder, hip girdle, or both) with normalization of erythrocyte sedimentation rate (ESR<30 mm/hr) and c-reactive protein (CRP =1.0 mg/dl), unless elevation of ESR and/or CRP are attributable to causes other than PMR (i.e., infection).
Patients who enroll in this trial will be treated with Tocilizumab at a dose of 8mg/kg once a month by intravenous infusion, in addition to steroid therapy, for a one year course of therapy. Steroids will be tapered according to a standardized protocol. In this protocol, the longest duration of corticosteroid therapy, in the absence of relapse or recurrence, would be 18 weeks. Evaluations will occur at screening, baseline visit (within 2 weeks of screening), two-weeks after baseline, and then monthly thereafter for 12 months. Upon completion of their final infusion of Tocilizumab therapy each patient will be seen at Month 13 and at Month 15, at which time their trial participation will be discontinued.
Disease- Specific Inclusion Criteria:
Patients must meet the following inclusion criteria to be eligible for study entry:
Diagnosed with polymyalgia rheumatica as defined by the Healey Criteria for classification of the disease and enrolled within one month of diagnosis.
Healey Criteria defined by:
1. Age greater than 50.
2. Erythrocyte sedimentation rate greater than 40 mm per hour.
3. Persistent pain (greater than or equal to one month) involving 2 of 3 areas (neck, shoulders, or pelvic girdle).
4. Morning stiffness lasting more than one hour.
5. Rapid response to prednisone, 20 mg daily or its equivalent, or less.
6. Absence of signs or symptoms of other connective tissue disease.
General Inclusion Criteria:
· Able and willing to give written informed consent and comply with the requirements of the study protocol.
· Men and women of reproductive potential must agree to use an acceptable method of birth control during treatment.
· Subjects must be willing to report pregnancies (females and male’s partners) that occur at any time during the trial
· Negative serum pregnancy test for women of child bearing potential (WOCBP). Women who are not of childbearing potential are excluded from this criterion. See below for definitions.
· WOCBP include any female who has not experienced menarche and who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or is not postmenopausal. Post menopause is defined as:
· Amenorrhea = 12 consecutive months without another cause
· For women with irregular menstrual periods and on hormone
replacement therapy (HRT), a documented serum follicle stimulating hormone (FSH) level = 35 mIU/mL.
· Women who are using oral contraceptives, other hormonal contraceptives (vaginal products, skin patches, or implanted or injectable products), or mechanical products such as an intrauterine device or barrier methods (diaphragm, condoms, spermicides) to prevent pregnancy, or are practicing abstinence, or where their partner is sterile (e.g., vasectomy) should be considered to be of childbearing potential.
Patients will be excluded from the study based on the following criteria:
· Symptoms or diagnosis of temporal arteritis, including headache, jaw claudication, hyperesthesia of scalp, abnormal palpated temporal artery, visual disturbances, temporal artery biopsy positivity
· Concurrent rheumatoid arthritis
· Presence of rheumatoid factor and CCP
· Other inflammatory arthritis or other connective tissue diseases, such as but not limited to systemic lupus erythematosus, systemic sclerosis, vasculitis, polymyositis, dermatomyositis, mixed connective tissue disease
· Treatment of polymyalgia rheumatica with more than 20mg of daily prednisone or its equivalent at the time of screening
· Treatment with more than 30mg of daily prednisone or its equivalent since diagnosis. Treatment with 30mg of daily prednisone or its equivalent since diagnosis for more than 2 weeks.
· More than 4 weeks of corticosteroid therapy prior to enrollment
· History of bowel perforation within the past five years.
· Active diverticulitis.
· Pre-existing or recent onset demyelinating disorders