30,000 Children with Form Of Juvenile Rheumatoid Arthritis May Have New Treatment Option
|
|
Anakinra may be effective in the treatment of an estimated 30,000 children with a certain form of juvenile arthritis, according to research presented this week at the American College of Rheumatology Annual Scientific Meeting in San Francisco, Calif.
Systemic onset juvenile idiopathic arthritis (often referred to as systemic-onset juvenile rheumatoid arthritis or Still’s disease) affects about 10 percent of children with arthritis. It begins with a recurrent fever that can be 103° F or higher, often accompanied by a pink rash that comes and goes. Systemic onset JIA may cause inflammation of the internal organs as well as the joints. Swelling of the joints may not be present initially, and may appear months or even years after the onset of fevers. Anemia (a low red blood cell count) and elevated white blood cell counts are also typical. Arthritis may persist despite the fevers and other systemic symptoms going away.
In a recent multicenter, randomized, double-blind trial, researchers compared the effectiveness of a one-month treatment with anakinra (Kineret)—which was delivered at 2 milligrams per kilogram, subcutaneously, each day with a maximum of 100 milligrams—to a placebo in two groups of children, each containing 12 patients with JIA. Treatment was blinded so that neither the children nor the investigators knew which injection was being given. After 1 month, patients were allowed to continue un-blinded therapy for another 11 months.
Researchers defined response to the therapy as at least 30 percent improvement in a set of measures of disease activity called the pediatric ACR core-set criteria. In addition to this ACR30 response, other measures of response included resolution of fever and systemic symptoms for at least eight days, and at least 50 percent decrease or normalization in two laboratory measures of inflammation, the C-reactive protein and erythrocyte sedimentation rate, when compared to the baseline.
After one month of treatment, researchers noticed a significant difference in the response rate between patients treated with anakinra and those given placebo. Eight out of 12 patients receiving anakinra improved according to the criteria used to define response, compared to only one of 12 patients receiving placebo.
During the double-blind phase, the number of adverse events, mainly pain caused from the injections, was found to be similar in both groups. Ten patients from the placebo group switched to anakinra at the end of the first month of the trial, and of those, nine were considered responders at the end of the second month.
Of those patients who eventually took anakinra during the study, eight discontinued taking medication before the end of month 12 of the trial: two because of pain from the injections; one due to symptoms leading to the diagnosis of Crohn’s disease; one due to liver disease; and four due to a lack of effectiveness or disease flare.
Further review showed that those who responded well to treatment had the highest blood concentrations of anakinra.
“IL-1 blockade by anakinra was well tolerated and resulted in a significant higher proportion of significant improvement than placebo in children with SO-JIA following one month of treatment,” says Pierre Quartier, MD, praticien hospitalier (consultant), coordinator of the French; National Reference Center for Juvenile Arthritis Pediatric; Immuno-Hematology and Rheumatology Unit Necker-Enfants Malades; Hospital Assistance Publique Hopitaux de Paris, Paris, France, and lead investigator in the study. “Over the next 11 months, a significant proportion of patients were able to stop or reduce the dose of steroids, but in some other cases, the disease flared when the dose of steroids was tapered, which means that other therapeutic approaches are needed in some cases”
Patients should talk to their rheumatologists to determine their best course of treatment.
The ACR is an organization of and for physicians, health professionals, and scientists that advances rheumatology through programs of education, research, advocacy and practice support that foster excellence in the care of people with or at risk for arthritis and rheumatic and musculoskeletal diseases. For more information on the ACR’s annual meeting, see http://www.rheumatology.org/annual.
Editor’s Notes: Dr. Quartier will present this research during the ACR Annual Scientific Meeting at the Moscone Center from 4:45 – 5:00 PM on Monday, October 2, in Room 104. Dr. Quartier will be available for media questions and briefing at 1:30 PM on Monday, October 27, in the on-site press conference room, 114.
Presentation Number: 1245
A multicentric, double-blind trial of Anakinra versus placebo in Systemic-Onset Juvenile Idiopathic Arthritis (ANAJIS trial): efficacy and tolerance over 12 months
Pierre Quartier1, Florence Allantaz2, Rolando Cimaz3, Pascal Pillet4, Agnes Duquesne3, Agnes Mogenet1, Claude Messiaen1, Christophe Bardin5, Jean-Marc Treluyer1, Paul Landais1, Virginia Pascual2. 1Hopital Necker-Enfants Malades, Paris, France; 2Baylor Institute, Dallas, TX; 3Hopital Edouard Herriot, Lyon, France; 4Hopital Pellegrin, Bordeaux, France; 5Hotel Dieu, Paris, France
Purpose: To investigate efficacy and safety of anakinra in Systemic-Onset Juvenile Idiopathic Arthritis (SOJIA) patients. To assess treatment effect on gene expression profiling
Methods: Multicenter randomized double-blind trial. The primary objective was to compare the efficacy of a one-month treatment with anakinra (2 mg/kg subcutaneoulsy daily, maximum 100 mg) to a placebo between 2 groups of 12 patients each. Response was defined by 30% improvement of pediatric ACR core-set criteria for JIA, resolution of fever and systemic symptoms for at least 8 days and normalization or a decrease of at least 50% of both CRP and first hour ESR compared to baseline. Intention-to-treat analysis. Secondary objectives included tolerance and efficacy assessment over 12 months, pharmacokinetic analyses and treatment effect on blood gene expression profiling.
Results: At one month, there was a significant difference in the response rate between patients treated with anakinra (8/12) and placebo (1/12). During the double-blind phase, the number of adverse events, mainly pain to injections, was similar between both groups. Ten patients from the placebo group switched to anakinra at Month 1 and 9 were responders at month 2. Eight patients discontinued anakinra before Month 12: painful injections during the double-blind phase (2 patients, both on placebo), ileocolic symptoms leading to the diagnosis of Crohn’s disease (1 patient), transient hepatic cytolysis (one case), lack of efficacy or a disease flare (4 cases). Pharmacokinetic analyses showed the highest concentration of anakinra in good responders. The SOJIA signature observed at day 1 rapidly wore off upon initiation of anakinra treatment. Gene expression profile analyses showed clear differences between responders and non responders.
Conclusions: Anakinra is effective in children with SOJIA. Gene expression profile analyses showed a set of gene pathways dysregulated in SOJIA whose expression dramatically changed upon anakinra treatment.
Disclosure Block: P. Quartier, None; F. Allantaz, None; R. Cimaz, None; P. Pillet, None; A. Duquesne, None; A. Mogenet, None; C. Messiaen, None; C. Bardin, None; J. Treluyer, None; P. Landais, None; V. Pascual, None.
Presentation Number: Control 577
A multicentric, double-blind trial of Anakinra versus placebo in Systemic-Onset Juvenile Idiopathic Arthritis (ANAJIS trial): efficacy and tolerance over 12 months
Pierre Quartier1, Florence Allantaz2, Rolando Cimaz3, Pascal Pillet4, Agnes Duquesne3, Agnes Mogenet1, Claude Messiaen1, Christophe Bardin5, Jean-Marc Treluyer1, Paul Landais1, Virginia Pascual2. 1Hopital Necker-Enfants Malades, Paris, France; 2Baylor Institute, Dallas, TX; 3Hopital Edouard Herriot, Lyon, France; 4Hopital Pellegrin, Bordeaux, France; 5Hotel Dieu, Paris, France
Purpose: To investigate efficacy and safety of anakinra in Systemic-Onset Juvenile Idiopathic Arthritis (SOJIA) patients. To assess treatment effect on gene expression profiling
Methods: Multicenter randomized double-blind trial. The primary objective was to compare the efficacy of a one-month treatment with anakinra (2 mg/kg subcutaneoulsy daily, maximum 100 mg) to a placebo between 2 groups of 12 patients each. Response was defined by 30% improvement of pediatric ACR core-set criteria for JIA, resolution of fever and systemic symptoms for at least 8 days and normalization or a decrease of at least 50% of both CRP and first hour ESR compared to baseline. Intention-to-treat analysis. Secondary objectives included tolerance and efficacy assessment over 12 months, pharmacokinetic analyses and treatment effect on blood gene expression profiling.
Results: At one month, there was a significant difference in the response rate between patients treated with anakinra (8/12) and placebo (1/12). During the double-blind phase, the number of adverse events, mainly pain to injections, was similar between both groups. Ten patients from the placebo group switched to anakinra at Month 1 and 9 were responders at month 2. Eight patients discontinued anakinra before Month 12: painful injections during the double-blind phase (2 patients, both on placebo), ileocolic symptoms leading to the diagnosis of Crohn’s disease (1 patient), transient hepatic cytolysis (one case), lack of efficacy or a disease flare (4 cases). Pharmacokinetic analyses showed the highest concentration of anakinra in good responders. The SOJIA signature observed at day 1 rapidly wore off upon initiation of anakinra treatment. Gene expression profile analyses showed clear differences between responders and non responders.
Conclusions: Anakinra is effective in children with SOJIA. Gene expression profile analyses showed a set of gene pathways dysregulated in SOJIA whose expression dramatically changed upon anakinra treatment.
Disclosure Block: P. Quartier, None; F. Allantaz, None; R. Cimaz, None; P. Pillet, None; A. Duquesne, None; A. Mogenet, None; C. Messiaen, None; C. Bardin, None; J. Treluyer, None; P. Landais, None; V. Pascual, None.
Source: American College of Rheumatology (ACR)
Print Version
Tell-a-Friend comments powered by Disqus
