Rheumatoid Arthritis: Henrickson M

Ruperto N, Lovell DJ, Cuttica R, Wilkinson N, Woo P, Espada G, Wouters C, Silverman ED, Balogh Z, Henrickson M, Apaz MT, Baildam E, Fasth A, Gerloni V, Lahdenne P, Prieur AM, Ravelli A, Saurenmann RK, Gamir ML, Wulffraat N, Marodi L, Petty RE, Joos R, Zulian F, McCurdy D, Myones BL, Nagy K, Reuman P, Szer I, Travers S, Beutler A, Keenan G, Clark J, Visvanathan S, Fasanmade A, Raychaudhuri A, Mendelsohn A, Martini A, Giannini EH, Anonymous00187, Anonymous00188. · IRCCS, Istituto G. Gaslini, Genoa, Italy. · Arthritis Rheum. · Pubmed #17763439 links to  free full text

Abstract: OBJECTIVE: To evaluate the safety and efficacy of infliximab in the treatment of juvenile rheumatoid arthritis (JRA). METHODS: This was an international, multicenter, randomized, placebo-controlled, double-blind study. One hundred twenty-two children with persistent polyarticular JRA despite prior methotrexate (MTX) therapy were randomized to receive infliximab or placebo for 14 weeks, after which all children received infliximab through week 44. Patients received MTX plus infliximab 3 mg/kg through week 44, or MTX plus placebo for 14 weeks followed by MTX plus infliximab 6 mg/kg through week 44. RESULTS: Although a higher proportion of patients in the 3 mg/kg infliximab group than in the placebo group had achieved responses according to the American College of Rheumatology (ACR) Pediatric 30 (Pedi 30) criteria for improvement at week 14 (63.8% and 49.2%, respectively), the between-group difference in this primary efficacy end point was not statistically significant (P = 0.12). By week 16, after the crossover from placebo to infliximab 6 mg/kg when all patients were receiving infliximab, an ACR Pedi 30 response was achieved in 73.2% of all patients. By week 52, ACR Pedi 50 and ACR Pedi 70 responses had been reached in 69.6% and 51.8%, respectively, of patients. Infliximab was generally well tolerated, but the safety profile of infliximab 3 mg/kg appeared less favorable than that of infliximab 6 mg/kg, with more frequent occurrences of serious adverse events, infusion reactions, antibodies to infliximab, and newly induced antinuclear antibodies and antibodies to double-stranded DNA observed with the 3 mg/kg dose. CONCLUSION: While infliximab at 3 mg/kg and 6 mg/kg showed durable efficacy at 1 year, achievement of the primary efficacy end point at 3 months did not differ significantly between infliximab-treated and placebo-treated patients. Safety data indicated that the 6-mg/kg dose may provide a more favorable risk/benefit profile. These results warrant further investigation in children with JRA.

Henrickson M, Reiff A. · Division of Rheumatology, Children's Hospital Central California, Madera, California 93638-8762, USA. · J Rheumatol. · Pubmed #15468375 No free full text.

Abstract: OBJECTIVE: For many children enthesitis-related arthritis (ERA) causes substantial morbidity, and conventional treatments frequently offer limited efficacy. Tumor necrosis factor-alpha (TNF-alpha) has been found to play a central role in the spondyloarthritides. We investigated the longterm efficacy of the TNF fusion protein etanercept in the treatment of patients with ERA refractory to disease modifying antirheumatic drug (DMARD) therapy. METHODS: Eight patients with active, inflammatory ERA were treated in an open-label pilot trial of twice weekly subcutaneous injections (dosing range of 25 to 37.5 mg twice weekly, 0.2-0.8 mg/kg/dose) of etanercept for 2 years. Outcome measures included duration of morning stiffness, active joint count, hemoglobin, and erythrocyte sedimentation rate (ESR). Patients were permitted concomitant nonsteroidal antiinflammatory drugs (NSAID) and DMARD at stable doses. RESULTS: Treatment with etanercept resulted in significant improvement in active joint count, hemoglobin, and ESR in all 8 patients within 2 months. Additionally, all patients noted increased mobility and overall well being. Improvement in morning stiffness did not achieve statistical significance. One patient was lost to followup after completing one year of the study. The remaining 7 patients had sustained statistically significant efficacy for active joint count, hemoglobin, and ESR throughout the entire 2-year trial. All patients tolerated etanercept with no side effects. CONCLUSION: Despite limited power, these results indicate that etanercept provided a rapid clinical response in our cohort of patients with refractory ERA, who achieved sustained efficacy over a 2-year period.

Shishov M, Henrickson M, Burgos-Vargas R, Rubio-Pérez N, Baca V, Romero-Feregrino R, Solís-Vallejo E, Huang B, Grom AA, Lovell DJ. · Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA. · Clin Exp Rheumatol. · Pubmed #18173929 No free full text.

Abstract: OBJECTIVE: To investigate if the persistence of systemic features is longer in Hispanic children with systemic juvenile idiopathic arthritis (S-JIA) than in non-Hispanic children with S-JIA and to determine early predictors of systemic and articular disease. METHODS: We performed a multi-center retrospective chart review of patients followed in six pediatric rheumatology centers with onset of S-JIA from 1974 to 2004. Patients were included in the study if they had been followed for > or = 1 year after disease onset. Information collected included demographic, clinical, laboratory and treatment data. Systemic features included fever, rash, lymphadenopathy, hepatosplenomegaly, pericarditis, and pleuritis. RESULTS: Of the 159 S-JIA patients screened, 120 (75%) met our inclusion criteria. There were 65 boys and 55 girls. The mean follow-up period for Hispanic patients was 5.7 years (SD 4.0) and for non-Hispanic patients was 8.6 years (SD 7.2). There was no significant difference in the presence of systemic features between Hispanic and non-Hispanic patients at 0.5, 1, 2, 4, 6, 8, and 10 years of follow-up. Polyarthritis at the 6-month visit was predictive of systemic features (OR 9.7, 95% CI 1.16-81.35, p = 0.036) and polyarthritis (OR 5.6, 95% CI 1.42-21.8, p = 0.014) at last follow-up. CONCLUSION: In children with S-JIA, Hispanics did not demonstrate longer persistence of systemic features than non-Hispanics. Polyarthritis at 6 months strongly predicted the development of persistent systemic features and chronic polyarticular disease.

Kimura Y, Pinho P, Walco G, Higgins G, Hummell D, Szer I, Henrickson M, Watcher S, Reiff A. · Joseph M. Sanzari Children's Hospital at Hackensack University Medical Center, Hackensack, New Jersey 07601, USA. · J Rheumatol. · Pubmed #15868633 No free full text.

Abstract: OBJECTIVE:. To assess the efficacy and safety of etanercept in a large cohort of children with refractory systemic onset juvenile rheumatoid arthritis (SOJRA). METHODS: Standardized questionnaires were sent to US pediatric rheumatologists about patients with SOJRA treated with etanercept. Data were collected at baseline and at the last visit on etanercept. Response to treatment was assessed and compared to baseline as the mean percentage reduction in the following: acute phase reactants, prednisone dose, active joint count, and physician global assessment of disease activity. Response was defined as poor if the mean reduction was < 30%, fair if 30% to < 50%, good if 50% to < 70%, and excellent if > 70%. RESULTS: We analyzed data obtained by survey of 82 SOJRA patients treated with etanercept for a mean of 25 months. Poor response to treatment was observed in 45% of the children, fair response in 9%, good in 13%, and excellent in 33%. Baseline steroid therapy could be discontinued in 27/59 (46%) patients. One or more disease flares occurred in 45% of all patients. Twenty-nine patients (35%) discontinued therapy, mostly due to lack of response or flare. There were 32 adverse event reports, most not considered serious, except for 2 cases of macrophage activation syndrome. CONCLUSION: In this cohort of children with SOJRA, 46% had a good or excellent response, and most were able to reduce concomitant corticosteroid doses. The response to etanercept was fair or poor in more than half our study population, and disease flares were common. Due to the unique cytokine profile of SOJRA, tumor necrosis factor blockade may not be the optimal therapeutic approach for children with treatment-resistant SOJRA.