Rheumatoid Arthritis: Stein LD

Lovell DJ, Giannini EH, Reiff A, Jones OY, Schneider R, Olson JC, Stein LD, Gedalia A, Ilowite NT, Wallace CA, Lange M, Finck BK, Burge DJ, Anonymous00012. · Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229-3039, USA. · Arthritis Rheum. · Pubmed #12528122 links to  free full text

Abstract: OBJECTIVE: To evaluate the long-term efficacy and safety of etanercept in children with juvenile rheumatoid arthritis (JRA) participating in an ongoing multicenter, open-label, extended-treatment trial. All patients had been participants in an initial randomized efficacy and safety trial of etanercept. METHODS: Etanercept was administered at a dosage of 0.4 mg/kg (maximum 25 mg) subcutaneously twice each week. Safety and efficacy evaluations were performed every 3-4 months. The JRA 30% definition of improvement (DOI) was defined as improvement of > or =30% in at least 3 of 6 response variables used to assess disease activity, with no more than 1 variable worsening by more than 30%. RESULTS: At the time of analysis, 48 of the 58 patients (83%) were still enrolled in the study; 43 of them (74%) had completed 2 years of treatment. Of these 43 patients, 81% met the JRA 30% DOI, 79% met the JRA 50% DOI, and 67% met the JRA 70% DOI. Ten children started low-dose methotrexate after year 1. Of the 32 children taking prednisone, the dosage was decreased to <5 mg/day in 26 (81%). Two children had serious infections (varicella with aseptic meningitis in one and complicated sepsis in the other). In general, adverse events were of the types seen in a general pediatric patient population. CONCLUSION: Children with severe, longstanding, methotrexate-resistant polyarticular JRA demonstrated sustained clinical improvement with >2 years of continuous etanercept treatment. Etanercept was generally well-tolerated. There were no increases in the rates of adverse events over time. However, children taking etanercept should be monitored closely for infections.

Lovell DJ, Giannini EH, Reiff A, Cawkwell GD, Silverman ED, Nocton JJ, Stein LD, Gedalia A, Ilowite NT, Wallace CA, Whitmore J, Finck BK. · Children's Hospital Medical Center, Cincinnati, OH 45229-3039, USA. · N Engl J Med. · Pubmed #10717011 links to  free full text

Abstract: BACKGROUND: We evaluated the safety and efficacy of etanercept, a soluble tumor necrosis factor receptor (p75):Fc fusion protein, in children with polyarticular juvenile rheumatoid arthritis who did not tolerate or had an inadequate response to methotrexate. METHODS: Patients 4 to 17 years old received 0.4 mg of etanercept per kilogram of body weight subcutaneously twice weekly for up to three months in the initial, open-label part of a multicenter trial. Those who responded to treatment then entered a double-blind study and were randomly assigned to receive either placebo or etanercept for four months or until a flare of the disease occurred. A response was defined as an improvement of 30 percent or more in at least three of six indicators of disease activity, with no more than one indicator worsening by more than 30 percent. RESULTS: At the end of the open-label study, 51 of the 69 patients (74 percent) had had responses to etanercept treatment. In the double-blind study, 21 of the 26 patients who received placebo (81 percent) withdrew because of disease flare, as compared with 7 of the 25 patients who received etanercept (28 percent) (P=0.003). The median time to disease flare with placebo was 28 days, as compared with more than 116 days with etanercept (P<0.001). In the double-blind study, there were no significant differences between the two treatment groups in the frequency of adverse events. CONCLUSIONS: Treatment with etanercept leads to significant improvement in patients with active polyarticular juvenile rheumatoid arthritis. Etanercept is well tolerated by pediatric patients.

Sherry DD, Stein LD, Reed AM, Schanberg LE, Kredich DW. · University of Washington, Seattle, USA. · Arthritis Rheum. · Pubmed #10555028 links to  free full text

Abstract: OBJECTIVE: To determine if intraarticular (i.a.) injection of triamcinolone hexacetonide (steroids) used early in the course of pauciarticular juvenile rheumatoid arthritis (pauci JRA) is associated with less leg length discrepancy (LLD) or thigh circumference discrepancy (TCD). METHODS: Children with pauci JRA who had asymmetric lower-extremity arthritis diagnosed before age 7 years in Seattle, Washington (WA; n = 16) and in Chapel Hill and Durham, North Carolina (NC; n = 14) were retrospectively identified. WA children were given i.a. steroids within 2 months of diagnosis; the injections were repeated if synovitis recurred in the same joint or in a different joint. These children were compared with NC children who were not treated with i.a. steroids. Thigh circumference was measured at 10 cm above the patella, and leg length was measured from the anterior superior iliac spine to the mid-medial malleolus, by a single observer. LLD and TCD are reported as the percentage of difference between leg measurements in each subject. RESULTS: The WA and NC subjects had comparable disease severity and duration of followup (in months). Twelve WA children had subsequent i.a. steroid injections (mean 3.25 injections per child over mean +/- SD 42 +/- 11 months). The WA subjects had significantly less LLD (P = 0.005, by Student's 2-sided t-test) and prescriptions for shoe lifts (P = 0.002, by Fisher's 2-sided exact test). There was not a significant difference in TCD between the 2 groups (P = 0.139, by Student's 2-sided t-test). Similar findings were obtained when the analysis was limited to children with monarticular knee arthritis. CONCLUSION: Early and continued use of i.a. steroids may be associated with less LLD in young children with pauci JRA. This may indicate decreased duration of synovitis.

Lovell DJ, Reiff A, Jones OY, Schneider R, Nocton J, Stein LD, Gedalia A, Ilowite NT, Wallace CA, Whitmore JB, White B, Giannini EH, Anonymous00068. · Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229, USA. · Arthritis Rheum. · Pubmed #16732547 links to  free full text

Abstract: OBJECTIVE: Previous studies showed that etanercept treatment in patients with polyarticular-course juvenile rheumatoid arthritis (JRA) provided rapid clinical improvement that was sustained for up to 2 years. The goal of our study was to provide data on safety and efficacy after 4 years of etanercept treatment in patients with JRA. METHODS: Patients with active polyarticular-course JRA who participated in an efficacy study continued etanercept treatment in an open-label extension. Safety was assessed by measuring rates of serious adverse events (SAEs) and serious infections. Efficacy was assessed using the American College of Rheumatology (ACR) Pediatric 30 criteria for improvement and standard measures of disease activity. (The ACR Pediatric 30 criteria are defined as improvement of > or = 30% in at least 3 of 6 core response variables used to assess disease activity, with no more than 1 variable worsening by > or = 30%.) RESULTS: Of the 69 patients who enrolled in the original efficacy study, 58 patients (84%) enrolled in the extension, 34 patients received etanercept treatment for > or = 4 years, and 32 of these received complete efficacy assessments. The rate of SAEs was 0.13 per patient-year, and the rate of serious infections was 0.04 per patient-year, in a total etanercept exposure of 225 patient-years. Eighty-two percent of patients who received corticosteroids at any time during the extension were able to decrease their dosage to < or = 5 mg/day prednisone equivalent. Of the 32 patients with complete efficacy data who received etanercept for > or = 4 years, 94% achieved an ACR Pediatric 30 response and 78% achieved an ACR Pediatric 70 response at the last study visit. CONCLUSION: Etanercept offers an acceptable safety profile in children with polyarticular-course JRA and provides significant improvement in disease manifestations that are sustained for > or = 4 years.