Arthritis & Rheumatism, Volume 62,
November 2010 Abstract Supplement
Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Atlanta, Georgia November 6-11, 2010.
Anakinra in Adult Onset Stills Disease (AOSD). Clinically Beneficial Results in an Open, Randomized, Multicenter Study.
Nordstrom3, Dan C., Knight11, Ann, Luukkainen8, Reijo, Vollenhoven5, Ronald V., Rantalaiho9, Vappu, Karjalainen7, Anna, Brun2, Johan
Central Finland Central Hospital, Finland
Umeå University Hospital, Sweden
Uppsala University Hospital, Sweden
Haukeland University Hospital, Norway
Helsinki Univerity Central Hospital, Finland
Helsinki University Central Hospital, Finland
Karolinska Hospital, Sweden
Martina Hansens Hospital, Norway
Oulu University Hospital, Finland
Rauma Hospital, Finland
Tampere University Hospital, Finland
AOSD is a rare systemic inflammatory disease of unknown cause characterized by spiking fevers, polyarthritis, evanescent rash, and other multiorgan involvement. The outcome is unpredictable and varies from monophasic, remitting/relapsing to chronically progressing. No etiology has emerged but high levels of pro-inflammatory cytokines (IL-1, IL-6, IL-18) involving possible polymorphisms, and acute phase reactants have been proposed as being pathogenetically relevant. Frequently, systemic immunosuppressive therapy is required for treatment, but for patients irresponsive to systemic steroids and immunosuppression, especially IL-1 suppression (anakinra) has given even striking responses. This is the first randomized study comparing IL-1 suppression therapy with traditional DMARDs.
To follow the changes in clinical status and disease activity in patients receiving anakinra, compared to those of a traditional DMARD (methotrexate, azathioprine, leflunomide, or cyclosporin A) in addition to corticosteroids in patients with corticosteroid dependent, refractory AOSD.
Open 24 week, randomized, comparative, multicenter study. 22 patients on corticosteroids were randomized to receive anakinra (n=12) or DMARD (n=10). Patients entered the study only if considered refractory to corticosteroids (prednisolone equivalent >=10 mg/day for at least two months after disease onset). Primary end point identified the proportion of patients reaching remission of disease after two months of study treatment (stated as afebrile [<=37°C of body temperature], acute phase reactants [C-reactive protein, ferritin] within normal limits, and joint scores being normal). Secondary end points included identification of patients reaching remission at two consecutive visits during 24 weeks, follow-up of acute phase reactants and corticosteroid dosage and identifying changes in disease related parameters such as general health, HAQ and SF-36.
Patient groups (anakinra vs. DMARD) were comparable except regarding baseline ferritin levels (354, range 181740 vs. 186, range 17680) and baseline prednisolone dose (22.5 mg, range 1060 vs. 18.5, range 1025), respectively. At week 4, 6/12 and 3/10 were in remission; at week 8, 7/12 and 5/10 were in remission; and at 24 weeks 6/12 and 2/10 were still in remission, respectively. In the Physical Health Summary of the SF-36 anakinra produced significantly more rapid and sustained responses compared to DMARD (p=0.011). Only patients on DMARDs (N=5) withdrew prematurely.
In refractory AOSD both DMARD therapy and especially anakinra showed good therapy responses during the 24 week intervention period. Responses were more robust with anakinra at 24 weeks with 50% of patients in strict remission according to criteria above. Withdrawals due to lack of efficacy occurred only in DMARD patients.
To cite this abstract, please use the following information:
Nordstrom, Dan C., Knight, Ann, Luukkainen, Reijo, Vollenhoven, Ronald V., Rantalaiho, Vappu, Karjalainen, Anna, et al; Anakinra in Adult Onset Stills Disease (AOSD). Clinically Beneficial Results in an Open, Randomized, Multicenter Study. [abstract]. Arthritis Rheum 2010;62 Suppl 10 :891