Kineret (anakinra) is able to rapidly halt disease activity and sustain long-term remission as an initial single treatment for patients with systemic juvenile idiopathic arthritis (sJIA), a five-year follow-up study says.
One month of Kineret was enough to stop disease activity in 55 percent of the patients. In the first year of follow-up, the disease became inactive in 76 percent of patients, while five years later, nearly all were free of active disease.
The study, “Treat‐to‐target using first‐line recombinant interleukin‐1 receptor antagonist monotherapy in new‐onset systemic juvenile idiopathic arthritis: results from a five year follow‐up study,” was published in the journal Arthritis and Rheumatology.
Kineret, an immunosuppressant marketed by Sobi, works by blocking the signals triggered by interleukin-1 (IL-1), an inflammatory messenger implicated in sJIA.
Last year, the European Union extended Kineret’s use for children 8 months or older with sJIA — to be given alone or in combination with other anti-inflammatory and disease-modifying antirheumatic drugs (DMARDs).
The EU also authorized the medicine for rheumatoid arthritis, cryopyrin-associated periodic syndromes (CAPS), and other forms of sJIA.
In the U.S., the therapy is approved only for rheumatoid arthritis and CAPS, but not for sJIA.
Trials testing Kineret and other interleukin-blocking agents “reported complete inactive disease in only 30% of patients after the first year of therapy,” the researchers wrote.
However, more recent studies have revealed that “approximately 50% of new onset patients have inactive disease after one year and 70% after three years of therapy.”
There is evidence that activation of the immune system, including IL-1 signalling, is particularly important at the early stages of the disease, which makes researchers believe that early therapy with Kineret may be particularly beneficial.
To test this possibility, a team at the University Medical Centre Utrecht, in the Netherlands, launched an initial clinical study to evaluate Kineret as first-line therapy for newly diagnosed sJIA patients.
Given the promising results after a median follow-up of 32 months, the team decided to pursue a long-term efficacy study spanning five years of treatment.
This new study included 42 children (median age of 7 years), who were recently diagnosed with sJIA and did not respond well to non-steroid anti-inflammatory drugs (NSAIDs).
Initially, up to 200 mg a day of Kineret was injected under the skin. In case of persisting disease, glucorticoid therapy (prednisolone) was added, or patients switched to alternative treatments such as Ilaris (canakinumab) or Actemra/RoActemra (tocilizumab). The median follow-up period was 5.8 years.
Patients suspected of having sJIA were also included in the study. They lacked evident signs of arthritis but complained of joint pain, and had the clinical symptoms (e.g. spiking fever, rash) and laboratory findings to suggest they had the disease.
Those who reached inactive disease at three months on Kineret alone were tapered off for a month (alternate-day regimen) and subsequently stopped receiving the therapy.
Inactive disease was defined as having no active arthritis, morning stiffness or systemic symptoms, and normal blood levels of inflammation markers (erythrocyte sedimentation rate and C-reactive protein), as well as a physician’s assessment of no disease activity.
If a patient experienced a disease flare, Kineret treatment was restarted.
The results showed that, on average, 33 days of treatment were needed for patients to reach inactive disease.
Overall, patients took the therapy for a median time of 6.1 months. At the end of the first year, 76% of the children showed no signs of active disease, and 52% had inactive disease off medication. Some patients had flares in the weeks or months after stopping Kineret, but flares were often resolved after re-initiating the therapy.
The data also revealed Kineret was able to keep most patients in long-term remission: 95% reached inactive disease at the end of three years in a 35-patient follow-up, and at the end of a five-year follow-up involving 25 patients. At five years, 72% of the patients were off the medication.
Four patients developed macrophage activation syndrome, or MAS, a severe complication marked by excessive activation and proliferation of immune system cells. Three of those patients did not respond to Kineret and were switched to other therapies in the first year. No patient stopped Kineret due to infections or other severe side effects.
A primary goal of the study was to see if Kineret was able to reduce the use of glucocorticoids, often associated with harmful side effects such as growth failure and obesity.
First-line treatment with Kineret limited the use of glucocorticoids, with about one-third of the patients needing additional systemic glucocorticoids to achieve or remain in a state of inactive disease. Two patients reported articular or joint damage, and none had growth deficits.
More than half of the patients (57.1%) needed Kineret and NSAIDs to stop disease activity over the studied period. Fourteen patients (33%) switched to other treatments or methotrexate combined with steroids.
The study found two possible predictors of an early response to Kineret: a high number of neutrophils (a type of white blood cells) before starting treatment, and reaching inactive disease after one month of treatment. Patients with these traits seemed more likely to remain in inactive disease one year after starting therapy.
First-line and short-course therapy with Kineret “results in quick and sustained inactive disease in the majority of systemic JIA patients, firmly reduces glucocorticoid use and prevents the development of disease and therapy-related damage in the long term,” the researchers concluded.
However, patients with normal neutrophil counts at the start of treatment, and/or those who do not response after one month of therapy “should be monitored closely, as they represent a risk group for persistent disease activity.”
