Clinical trial NCT03244709: Tocilizumab Dose-tapering and Interruption in Patients With Giant Cell Arteritis Achieving the Clinical Remission.
Official title: Tocilizumab Dose-tapering and Interruption in Patients With Giant Cell Arteritis Achieving the Clinical Remission: a Prospective, Pilot Study.
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Giant Cell Arteritis
Keywords: Giant cell arteritis,
Tocilizumab
Aortitis
Remission
Lead sponsor: Hospital of Prato
Sponsor class: OTHER
First posted: 2017-08-09
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: Interleukin-6 (IL-6), a pro-inflammatory cytokine, has been found to have a crucial role in the pathogenesis of Giant cel arteritis (GCA). Based on this rationale, several recent studies demonstrated the efficacy of tocilizumab (TCZ), an anti-IL-6 targeted monoclonal antibody, for the treatment of patients with refractory GCA. Confirming previous reports,in a recent retrospective study the investigators successfully treated 10 patient with refractory GCA with TCZ. All patients achieved a complete disease remission evaluated by clinical, laboratory, and positron emission tomography (PET). In a considerable number of GCA patients treated with corticosteroids (CS) the therapy may be interrupted with no disease flares. No data are available on the management of patients achieving the remission with TCZ.

Detailed description: Study design. Open-label, prospective, pilot study on patients with giant cell arteritis (GCA) resistant to corticosteroids (CS) .

Setting. Rheumatology department, Hospital of Prato, Prato, Italy. Treatment. All refractory GCA patients with or without involvement of aorta and its thoracic branches treated with intravenous TCZ at the dose of 8 mg/Kg/monthly or subcutaneous TCZ at the dose of 162 mg/weekly who achieved a stable remission over a 6-month period should receive reduced TCZ doses with the following schedules: intravenous TCZ tapering to 2 mg/Kg/monthly with drug withdrawal at month 4, and subcutaneous TCZ monthly reduction through the lengthening of injection intervals every 2, 3 , and 4 weeks, and with drug interruption at month 4.

Primary end-point. To investigate the maintenance of clinical remission after TCZ interruption over a 6-month follow-up period.

Secondary end-points. To assess the maintenance of clinical remission during the treatment, to evaluate the role of acute-phase reactants and PET in predicting the relapse and remission, and to assess the occurrence of adverse event (AEs).

Eligibility criteria: Inclusion Criteria:

- All consecutive patients meeting the 1990 ACR classification criteria for GCA.

Exclusion Criteria:

* Corticosteroid treatment during the previous 6 months.
* Uncontrolled diabetes.
* Uncontrolled hypertension.
* History of cancer within the past 5 years.
* History of frequent infections in the past.
* Positivity of screening procedures for latent tuberculosis infection.
* Uncontrolled dyslipidemia at baseline.
* Known intestinal diverticulosis.
* Concomitant hematologic disorders.

Primary outcomes:
measure: The percentage of patients maintaining the off-therapy clinical remission over the follow-up as expressed by absence of GCA symptoms and signs, normal ESR and CRP values, absence of arterial wall inflammation at PET examination
timeFrame: 6-month off-therapy period
Secondary outcomes:
measure: The percentage of patients achieving and maintaining the clinical remission during the treatment with TCZ as expressed by the absence of GCA symptoms and signs, normal ESR and CRP values, absence of arterial wall inflammation at PET examination
timeFrame: 12 months
measure: To compare the role of acute-phase reactants and 18F-FDG-PET in the evaluation of remission.
timeFrame: Months 6,12,18
measure: Number of participants with treatment-related adverse events as assessed by CTCAE v4.0" MeDRA 12.1.
timeFrame: Month 18
Other outcomes:
Locations:
city: Prato
country: Italy
facility: Fabrizio Cantini
state: Tuscany
Study officials:
References:
citation: Salvarani C, Cantini F, Hunder GG. Polymyalgia rheumatica and giant-cell arteritis. Lancet. 2008 Jul 19;372(9634):234-45. doi: 10.1016/S0140-6736(08)61077-6.
citation: Soussan M, Nicolas P, Schramm C, Katsahian S, Pop G, Fain O, Mekinian A. Management of large-vessel vasculitis with FDG-PET: a systematic literature review and meta-analysis. Medicine (Baltimore). 2015 Apr;94(14):e622. doi: 10.1097/MD.0000000000000622.
citation: Stone JH, Tuckwell K, Dimonaco S, Klearman M, Aringer M, Blockmans D, Brouwer E, Cid MC, Dasgupta B, Rech J, Salvarani C, Schett G, Schulze-Koops H, Spiera R, Unizony SH, Collinson N. Trial of Tocilizumab in Giant-Cell Arteritis. N Engl J Med. 2017 Jul 27;377(4):317-328. doi: 10.1056/NEJMoa1613849.
citation: Unizony S, Arias-Urdaneta L, Miloslavsky E, Arvikar S, Khosroshahi A, Keroack B, Stone JR, Stone JH. Tocilizumab for the treatment of large-vessel vasculitis (giant cell arteritis, Takayasu arteritis) and polymyalgia rheumatica. Arthritis Care Res (Hoboken). 2012 Nov;64(11):1720-9. doi: 10.1002/acr.21750.
citation: Loricera J, Blanco R, Hernandez JL, Castaneda S, Mera A, Perez-Pampin E, Peiro E, Humbria A, Calvo-Alen J, Aurrecoechea E, Narvaez J, Sanchez-Andrade A, Vela P, Diez E, Mata C, Lluch P, Moll C, Hernandez I, Calvo-Rio V, Ortiz-Sanjuan F, Gonzalez-Vela C, Pina T, Gonzalez-Gay MA. Tocilizumab in giant cell arteritis: Multicenter open-label study of 22 patients. Semin Arthritis Rheum. 2015 Jun;44(6):717-23. doi: 10.1016/j.semarthrit.2014.12.005. Epub 2014 Dec 27.
citation: Proven A, Gabriel SE, Orces C, O'Fallon WM, Hunder GG. Glucocorticoid therapy in giant cell arteritis: duration and adverse outcomes. Arthritis Rheum. 2003 Oct 15;49(5):703-8. doi: 10.1002/art.11388.