Anakinra Promising in Pediatric Inflammation

Response to anakinra treatment was rapid and sustained in most patients with adult-onset Still's disease and in a “significant proportion” of patients with systemic-onset juvenile idiopathic arthritis, according to a study.

The results suggest the treatment has the potential not only to alleviate symptoms of these diseases, but also to reduce steroid dosage, reported Dr. Thierry Lequerré of the department of rheumatology at the Centre Hôpitalier Universitaire Rouen (France) and colleagues.

The study assessed the efficacy and tolerability of anakinra in 20 systemic-onset juvenile idiopathic arthritis (SoJIA) patients (mean age, 12 years) and 15 adult-onset Still's disease (AoSD) patients (mean age, 38 years), all of whom had been treated previously with corticosteroids. All 20 of the SoJIA patients and 12 patients in the AoSD group were on steroids at the start of anakinra treatment. Disease-modifying antirheumatic drugs had also been used by all patients except the youngest child, and had been deemed ineffective or not very effective (Ann. Rheum. Dis. 2008;67:302-8).

Anakinra was started at a dosage of 100 mg/day in AoSD patients, and at dosages of 1-2 mg/kg per day (maximum, 100 mg/day) in SoJIA patients, with an increase after 2 months if there was no significant improvement. Data were collected at baseline, at 3 and 6 months after treatment initiation, and at the latest follow-up, with the mean follow-up time being approximately 14 months in all patients.

Response in patients with AoSD was defined as a resolution of systemic symptoms and an improvement of the American College of Rheumatology (ACR) score by at least 20%. In patients with SoJIA, response was defined as resolution of systemic symptoms and improvement of the Giannini's ACR pediatric criteria by at least 30% for polyarticular JIA activity assessment. If either the ACR or ACR pediatric scores showed less than 50% improvement, response was classified as “partial,” whereas “complete” response was defined as improvement of more than 50%.

Among the 20 SoJIA patients, 15 showed at least some improvement, noted the authors. “Clinical systemic features, including fever and rash, were resolved in 14 cases within the first 3 months.” However, the percentage of patients who achieved 30%, 50% and 70% improvement, according to ACR pediatric criteria, were 55%, 30% and 0% at 3 months respectively; 50%, 25% and 10% at 6 months, respectively; and 45%, 20% and 10% at the latest follow-up, respectively, they reported. By 6 months post treatment initiation, corticosteroid dosages in nine patients were reduced by 15%-78%.

Among the 15 AoSD patients, 11 (73%) “had a prompt and dramatic improvement in all disease markers,” they noted. A total of 9 of the 11 patients “achieved a complete response at 3 months; [as did] 10 of the 11 patients at 6 months; and 9 of the 11 patients at the latest follow-up.” In 2 of the 11 responders, corticosteroids could be stopped, and in 8 others, the dosage was reduced by 45%-95% from baseline.

Treatment withdrawal was reported for five SoJIA and four AoSD patients because of intolerance, side effects, or lack of efficacy. There were several infections reported, including one case of visceral Leishmania and one case of varicella. Local pain or reactions were the most frequent adverse events.

“This is the largest such series and the first to analyze the effects of this treatment on SoJIA and AoSD patients, in parallel,” noted the authors. In comparing the two populations, they noted several differences that might account for the higher rate of response achieved by the adults, including the more common presence of fever and systemic symptoms in the adults, and the higher number of swollen, tender joints in the children. Another consideration is whether the dose or number of injections should have been increased in nonresponders, they added. “The lower response rate observed in SoJIA patients indicates that prospective, randomized, and controlled trials are needed, assessing, in particular, the pharmacokinetics of anakinra in children.”

The authors declared no competing interests in relation to the study.

The investigation “supports the anecdotal reports at scientific meetings of anakinra treatment failures [in SoJIA], as well as the dramatic benefit anakinra produced in responders,” noted Dr. Patricia Woo from University College London, in an editorial accompanying the article (Ann. Rheum. Dis. 2008;67:281-2).

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Response to anakinra treatment was rapid and sustained in most patients with adult-onset Still's disease and in a “significant proportion” of patients with systemic-onset juvenile idiopathic arthritis, according to a study.

The results suggest the treatment has the potential not only to alleviate symptoms of these diseases, but also to reduce steroid dosage, reported Dr. Thierry Lequerré of the department of rheumatology at the Centre Hôpitalier Universitaire Rouen (France) and colleagues.

The study assessed the efficacy and tolerability of anakinra in 20 systemic-onset juvenile idiopathic arthritis (SoJIA) patients (mean age, 12 years) and 15 adult-onset Still's disease (AoSD) patients (mean age, 38 years), all of whom had been treated previously with corticosteroids. All 20 of the SoJIA patients and 12 patients in the AoSD group were on steroids at the start of anakinra treatment. Disease-modifying antirheumatic drugs had also been used by all patients except the youngest child, and had been deemed ineffective or not very effective (Ann. Rheum. Dis. 2008;67:302-8).

Anakinra was started at a dosage of 100 mg/day in AoSD patients, and at dosages of 1-2 mg/kg per day (maximum, 100 mg/day) in SoJIA patients, with an increase after 2 months if there was no significant improvement. Data were collected at baseline, at 3 and 6 months after treatment initiation, and at the latest follow-up, with the mean follow-up time being approximately 14 months in all patients.

Response in patients with AoSD was defined as a resolution of systemic symptoms and an improvement of the American College of Rheumatology (ACR) score by at least 20%. In patients with SoJIA, response was defined as resolution of systemic symptoms and improvement of the Giannini's ACR pediatric criteria by at least 30% for polyarticular JIA activity assessment. If either the ACR or ACR pediatric scores showed less than 50% improvement, response was classified as “partial,” whereas “complete” response was defined as improvement of more than 50%.

Among the 20 SoJIA patients, 15 showed at least some improvement, noted the authors. “Clinical systemic features, including fever and rash, were resolved in 14 cases within the first 3 months.” However, the percentage of patients who achieved 30%, 50% and 70% improvement, according to ACR pediatric criteria, were 55%, 30% and 0% at 3 months respectively; 50%, 25% and 10% at 6 months, respectively; and 45%, 20% and 10% at the latest follow-up, respectively, they reported. By 6 months post treatment initiation, corticosteroid dosages in nine patients were reduced by 15%-78%.

Among the 15 AoSD patients, 11 (73%) “had a prompt and dramatic improvement in all disease markers,” they noted. A total of 9 of the 11 patients “achieved a complete response at 3 months; [as did] 10 of the 11 patients at 6 months; and 9 of the 11 patients at the latest follow-up.” In 2 of the 11 responders, corticosteroids could be stopped, and in 8 others, the dosage was reduced by 45%-95% from baseline.

Treatment withdrawal was reported for five SoJIA and four AoSD patients because of intolerance, side effects, or lack of efficacy. There were several infections reported, including one case of visceral Leishmania and one case of varicella. Local pain or reactions were the most frequent adverse events.

“This is the largest such series and the first to analyze the effects of this treatment on SoJIA and AoSD patients, in parallel,” noted the authors. In comparing the two populations, they noted several differences that might account for the higher rate of response achieved by the adults, including the more common presence of fever and systemic symptoms in the adults, and the higher number of swollen, tender joints in the children. Another consideration is whether the dose or number of injections should have been increased in nonresponders, they added. “The lower response rate observed in SoJIA patients indicates that prospective, randomized, and controlled trials are needed, assessing, in particular, the pharmacokinetics of anakinra in children.”

The authors declared no competing interests in relation to the study.

The investigation “supports the anecdotal reports at scientific meetings of anakinra treatment failures [in SoJIA], as well as the dramatic benefit anakinra produced in responders,” noted Dr. Patricia Woo from University College London, in an editorial accompanying the article (Ann. Rheum. Dis. 2008;67:281-2).

ELSEVIER GLOBAL MEDICAL NEWS

Response to anakinra treatment was rapid and sustained in most patients with adult-onset Still's disease and in a “significant proportion” of patients with systemic-onset juvenile idiopathic arthritis, according to a study.

The results suggest the treatment has the potential not only to alleviate symptoms of these diseases, but also to reduce steroid dosage, reported Dr. Thierry Lequerré of the department of rheumatology at the Centre Hôpitalier Universitaire Rouen (France) and colleagues.

The study assessed the efficacy and tolerability of anakinra in 20 systemic-onset juvenile idiopathic arthritis (SoJIA) patients (mean age, 12 years) and 15 adult-onset Still's disease (AoSD) patients (mean age, 38 years), all of whom had been treated previously with corticosteroids. All 20 of the SoJIA patients and 12 patients in the AoSD group were on steroids at the start of anakinra treatment. Disease-modifying antirheumatic drugs had also been used by all patients except the youngest child, and had been deemed ineffective or not very effective (Ann. Rheum. Dis. 2008;67:302-8).

Anakinra was started at a dosage of 100 mg/day in AoSD patients, and at dosages of 1-2 mg/kg per day (maximum, 100 mg/day) in SoJIA patients, with an increase after 2 months if there was no significant improvement. Data were collected at baseline, at 3 and 6 months after treatment initiation, and at the latest follow-up, with the mean follow-up time being approximately 14 months in all patients.

Response in patients with AoSD was defined as a resolution of systemic symptoms and an improvement of the American College of Rheumatology (ACR) score by at least 20%. In patients with SoJIA, response was defined as resolution of systemic symptoms and improvement of the Giannini's ACR pediatric criteria by at least 30% for polyarticular JIA activity assessment. If either the ACR or ACR pediatric scores showed less than 50% improvement, response was classified as “partial,” whereas “complete” response was defined as improvement of more than 50%.

Among the 20 SoJIA patients, 15 showed at least some improvement, noted the authors. “Clinical systemic features, including fever and rash, were resolved in 14 cases within the first 3 months.” However, the percentage of patients who achieved 30%, 50% and 70% improvement, according to ACR pediatric criteria, were 55%, 30% and 0% at 3 months respectively; 50%, 25% and 10% at 6 months, respectively; and 45%, 20% and 10% at the latest follow-up, respectively, they reported. By 6 months post treatment initiation, corticosteroid dosages in nine patients were reduced by 15%-78%.

Among the 15 AoSD patients, 11 (73%) “had a prompt and dramatic improvement in all disease markers,” they noted. A total of 9 of the 11 patients “achieved a complete response at 3 months; [as did] 10 of the 11 patients at 6 months; and 9 of the 11 patients at the latest follow-up.” In 2 of the 11 responders, corticosteroids could be stopped, and in 8 others, the dosage was reduced by 45%-95% from baseline.

Treatment withdrawal was reported for five SoJIA and four AoSD patients because of intolerance, side effects, or lack of efficacy. There were several infections reported, including one case of visceral Leishmania and one case of varicella. Local pain or reactions were the most frequent adverse events.

“This is the largest such series and the first to analyze the effects of this treatment on SoJIA and AoSD patients, in parallel,” noted the authors. In comparing the two populations, they noted several differences that might account for the higher rate of response achieved by the adults, including the more common presence of fever and systemic symptoms in the adults, and the higher number of swollen, tender joints in the children. Another consideration is whether the dose or number of injections should have been increased in nonresponders, they added. “The lower response rate observed in SoJIA patients indicates that prospective, randomized, and controlled trials are needed, assessing, in particular, the pharmacokinetics of anakinra in children.”

The authors declared no competing interests in relation to the study.

The investigation “supports the anecdotal reports at scientific meetings of anakinra treatment failures [in SoJIA], as well as the dramatic benefit anakinra produced in responders,” noted Dr. Patricia Woo from University College London, in an editorial accompanying the article (Ann. Rheum. Dis. 2008;67:281-2).

ELSEVIER GLOBAL MEDICAL NEWS