Rapid responses to anakinra in patients with refractory adult‐onset Still's disease

Abstract

Objective. To assess the efficacy of anakinra treatment in patients with adult-onset Still's disease (AOSD) that is refractory to corticosteroids, methotrexate (MTX), and etanercept.Methods. Four patients with AOSD were treated with prednisone and MTX and 2 patients were also treated with etanercept for worsening symptoms and indicators of systemic inflammation. White blood cells (WBCs), C-reactive protein (CRP) levels and/or erythrocyte sedimentation rate, and ferritin levels were measured and, in 1 patient, serum creatinine levels were determined. Treatment with anakinra at 100 mg/day was initiated.Results. The index patient's disease was refractory to treatment with prednisone (30 mg/day) and MTX, with spiking fevers, rash, synovitis, a serum ferritin level of 8,400 ng/ml (normal <200), and a CRP level of 86 mg/liter (normal <8). Levels of interleukin-1␤ (IL-1␤), IL-1␣, IL-6, IL-1 receptor antagonist, and IL-18 were elevated. Just prior to anakinra treatment, the WBC count was 14,600/mm 3 , the CRP level was 86 mg/liter, and the ferritin level was 573 ng/ml, with daily spiking fevers to 104°F, rash, and swollen joints. Within hours of the first injection, the patient was afebrile and asymptomatic; within days, the WBC count, ferritin level, and CRP level decreased into the normal range.On 2 occasions, anakinra was withheld. Within a few days, the WBC count rose to >20,000/mm 3 with prominent neutrophilia, the CRP level rose to >200 mg/liter, and the ferritin level rose to >3,000 ng/ml. Upon restarting anakinra, the patient became afebrile, the WBC count fell to 8,000/mm 3 , the CRP level fell to <3 mg/liter, and the ferritin level fell to <300 ng/ml. Three additional patients with refractory AOSD who experienced rapid reductions in fever, symptoms, and markers of inflammation when treated with anakinra are reported.Conclusion. Refractory AOSD appears to be IL-1-mediated since anakinra decreases hematologic, biochemical, and cytokine markers and also produces rapid reductions in systemic and local inflammation. Reported efficacy of tumor necrosis factor-blocking therapies in AOSD may be due to a reduction in IL-1.Adult-onset Still's disease (AOSD), a rheumatologic condition found worldwide, is characterized by a variety of clinical features, including intermittent fever, arthritis, evanescent rash, sore throat, leukocytosis, and hepatic dysfunction, polyserositis, lymphadenopathy, splenomegaly, and other systemic symptoms. Because of the diverse presentation (1), classifications have been developed to standardize the diagnosis of AOSD. The most widely accepted criteria set, as presented by Yamaguchi and colleagues (2), is a compilation of major and minor criteria with the exclusion of infections, malignancies, and other rheumatic or systemic diseases. More recently, Fautrel and associates have proposed classification criteria utilizing diagnostic markers of serum ferritin and glycosylated ferritin, thought to be more specific for AOSD (3). These criteria are said to provide a sensitivity of 80.6% and a specifi...

The many worlds of reducing interleukin‐1

“…Clearly, the most marked responses to anakinra have been observed in patients with adult-onset Still's disease (9,10), macrophage activation syndrome, familial Mediterranean fever, or mutations in the NALP3 gene. These mutations can cause Muckle-Wells syndrome (15), neonatal-onset multisystem inflammatory disease (7), and familial cold autoinflammatory syndrome (16).…”

“…The mutation is also absent in patients with refractory adult-onset Still's disease, where a rapid resolution of the disease activity is observed within hours or days of treatment with anakinra (8)(9)(10)(11). Anakinra is now the treatment of choice in patients with steroidrefractory adult-onset Still's disease, mutations in NALP3, and Schnitzler's syndrome (van der Meer J: personal communication).…”

A rare presentation of adult onset Still’s disease in an elderly patient

“…A number of viruses, including EpsteinBarr virus, cytomegalovirus, hepatitis B, C and parvovirus B19 have been implicated. [1][2][3][4][5] In the case that we describe, even though EBV and CMV titer results showed the presence of latent infection, no causal relationship could be established. AOSD predominantly affects young adults between 16 and 35 years of age.…”

“…[6][7][8] Patients often present with fever (usually higher than 39C), evanescent rash, lymphadenopathy, sore throat, arthralgia, myalgia, arthritis and serositis. [1][2][3][4]9 In contrast, our patient presented initially with profound fatigue and weight loss.…”

“…1,5,9 Just as in the case that we describe, markers of inflammation such as ESR and CRP are often elevated. [1][2][3][4]9 White cell counts greater than 20¥10 9 cells/L are observed in only close to 1/3 of the patients. 1 Anemia of chronic disease and thrombocytosis have also been reported.…”