Clinical trial NCT01033656: Treatment of Refractory Adult-onset Still's Disease With Anakinra: a Randomized Study
Official title: An Open, Randomized Study Treating Refractory Adult-onset Still's Disease With Interleukin-1 Receptor Antagonist Anakinra (Kineret), Compared to an Established, Single Anti-rheumatic Drug Treatment
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Adult-Onset Still's Disease
Keywords: adult-onset Still's disease
anakinra
prednisolone
disease-modifying antirheumatic drug
methotrexate
efficacy
patients
Lead sponsor: University of Helsinki
Sponsor class: OTHER
Collaborators: name: Uppsala University Hospital
name: Helse Stavanger HF
name: Tampere University Hospital
name: Turku University Hospital
name: Oulu University Hospital
name: Kuopio University Hospital
name: Jyväskylä Central Hospital
name: Satakunta Central Hospital
name: University Hospital, Umeå
name: University Hospital, Linkoeping
First posted: 2009-12-16
Enrollment: 23
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: An open, randomized, parallel-group, comparative, multicentre study. Patients on corticosteroids (plus conventional therapy) will be randomized to receive anakinra (Kineret®), or one of the following: methotrexate, azathioprine, leflunomide, cyclosporin A or sulphasalazine. Patients enter the study if considered refractory to corticosteroids (prednisolone equivalent ≥10 mg/day) at the time of randomization.

The randomized phase of the study will be followed by an open-label extension (OLE) phase, to follow-up drug survival, efficacy, tolerability and disease-related parameters of long-term treatment with anakinra or one of the study DMARDs or a combination of study drugs for additional 28 weeks.

Detailed description: Product: Kineret (anakinra) Comparative agents: Methotrexate or azathioprine or leflunomide or cyclosporin A or sulphasalazine Protocol title: An open, randomized study treating refractory adult-onset Still's disease with IL-1ra anakinra (Kineret, compared to an established, single anti-rheumatic treatment Target Disease: Adult-onset Still's disease Patients: 23 patients diagnosed with AOSD, living in the four Nordic countries.

Study Objectives: To follow the changes in clinical status and disease activity in patients receiving anakinra, compared to those treated with an established DMARD, in addition to corticosteroids in patients with refractory AOSD. To compare the changes in disease-related parameters (global health, patient's assessment on disease, laboratory values) in the two randomized groups. To assess the safety of anakinra in AOSD. To follow-up drug survival, efficacy, tolerability and disease-related parameters of long-term treatment in AOSD (open phase).

Eligibility criteria: Inclusion Criteria:

* Must be diagnosed with AOSD according to preliminary classification by Yamaguchi (1992).
* Other diseases with similar symptoms must be excluded. Has been exposed to a corticosteroid for ≥2 months prior to randomization for AOSD.
* Needs a prednisolone dose ≥10 mg/day or equivalent, yet unacceptable disease activity determined by the investigator.
* Anti-TNF agents must be discontinued 4 to 8 weeks prior to commencing study medication.

Exclusion Criteria:

* Use of corticosteroids (prednisolone equivalent \<10 mg/day.
* History of recurrent or chronic infection, including:

  * tuberculosis
  * any malignancy
  * any other major chronic inflammatory disease syndrome
  * drug or alcohol abuse
  * known positivity for hepatitis B, C or HIV.
* Use of anti-TNF agents during ≤4 weeks (etanercept) or≤8 weeks (infliximab or adalimumab) prior to randomization.

Primary outcomes:
measure: Number of patients reaching remission of the disease, after eight weeks of the randomized study treatment (Remission: afebrile and normalization of acute phase reactants)
timeFrame: 8 weeks
Secondary outcomes:
Other outcomes:
Locations:
city: Uppsala
country: Sweden
facility: Ann Kataja Knight
Study officials:
affiliation: Helsinki University Hospital, Department of Medicine
name: Dan C Nordstrom, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Nordstrom D, Knight A, Luukkainen R, van Vollenhoven R, Rantalaiho V, Kajalainen A, Brun JG, Proven A, Ljung L, Kautiainen H, Pettersson T. Beneficial effect of interleukin 1 inhibition with anakinra in adult-onset Still's disease. An open, randomized, multicenter study. J Rheumatol. 2012 Oct;39(10):2008-11. doi: 10.3899/jrheum.111549. Epub 2012 Aug 1.