Skip to main content
Top
Published in: Pediatric Rheumatology 1/2013

Open Access 01-12-2013 | Research

Superior efficacy of Adalimumab in treating childhood refractory chronic uveitis when used as first biologic modifier drug: Adalimumab as starting anti-TNF-α therapy in childhood chronic uveitis

Authors: Gabriele Simonini, Andrea Taddio, Marco Cattalini, Roberto Caputo, Cinzia de Libero, Fulvio Parentin, Ilaria Pagnini, Loredana Lepore, Rolando Cimaz

Published in: Pediatric Rheumatology | Issue 1/2013

Login to get access

Abstract

Background

Nonetheless biologic modifier therapies are available treatment strategies for sight-threatening uveitis in children, the lack of evidence from head-to-head randomized controlled studies limits our understanding of timing of therapy when to commence therapy, which agent to choose and how long to continue treatment, and, in case of failure, if switching to another anti-TNF-α strategy might be eventually an option. Our aim was to compare the efficacy of Adalimumab when used as first anti-TNFα therapy versus Adalimumab used after the failure of a previous anti-TNFα (Infliximab) in an open-label, comparative, multi-center, cohort study of childhood chronic uveitis.

Methods

26 patients (14 F, 12 M; median age: 8.6 years) with refractory, non-infectious active uveitis were enrolled. Due to the refractory course of uveitis to previous DMARD treatment, Group 1 received Adalimumab (24 mg/sq mt, every 2 weeks), as first anti-TNFα choice; Group 2 received Adalimumab, as second anti-TNFα drug, due to the loss of efficacy of Infliximab, administered after a period of at least 1 year. Both groups received Adalimumab for at least 1 year of treatment. Primary outcome was, once remission was achieved, the time to a first relapse.

Results

14 children (10 with JIA, 3 with idiopathic uveitis, 1 with Behçet’s disease) were recruited in Group 1; 12 children (7 with JIA, 3 with idiopathic uveitis, 1 with early-onset sarcoidosis, 1 with Behçet’s disease) in Group 2. Group 2 showed a lower probability to steroid discontinuation during the first 12 months of treatment (Mantel-Cox χ24.12, p<0.04). In long-term follow-up, Group 1 had higher probability of uveitis remission during the time of treatment on Adalimumab (median ±SE: 18 ± 1.1 vs 4 ±0.6 months, CI 95%: 15.6- 27.5 vs 2.7-5.2, Mantel-Cox χ210.12, p<0.002).

Conclusions

Even if limited to a relatively small group, our study suggests a better efficacy of Adalimumab when used as first anti-TNFα treatment in childhood chronic uveitis.
Appendix
Available only for authorised users
Literature
1.
go back to reference Cunnigham ET: Uveitis in children. Ocul Immunol Inflamm. 2000, 8: 251-261. 10.1076/ocii.8.4.251.6459.CrossRef Cunnigham ET: Uveitis in children. Ocul Immunol Inflamm. 2000, 8: 251-261. 10.1076/ocii.8.4.251.6459.CrossRef
2.
go back to reference Lyon F, Gale RP, Lightman S: Recent developments in the treatment of uveitis: an update. Expert Opin Investig Drugs. 2009, 18: 609-616. 10.1517/14728220902852570.CrossRefPubMed Lyon F, Gale RP, Lightman S: Recent developments in the treatment of uveitis: an update. Expert Opin Investig Drugs. 2009, 18: 609-616. 10.1517/14728220902852570.CrossRefPubMed
3.
go back to reference Simonini G, Cantarini L, Lo Russo M: Current therapeutic approaches to autoimmune chronic uveitis in children. Autoimmun Rev. 2010, 9: 674-683. 10.1016/j.autrev.2010.05.017.CrossRefPubMed Simonini G, Cantarini L, Lo Russo M: Current therapeutic approaches to autoimmune chronic uveitis in children. Autoimmun Rev. 2010, 9: 674-683. 10.1016/j.autrev.2010.05.017.CrossRefPubMed
4.
go back to reference Zierhut M, Doycheva D, Biester S, Stübiger N, Kümmerle-Deschner J, Deuter C: Therapy of uveitis in children. Int Ophthalmol Clin. 2008, 48: 131-152. 10.1097/IIO.0b013e31817d7107.CrossRefPubMed Zierhut M, Doycheva D, Biester S, Stübiger N, Kümmerle-Deschner J, Deuter C: Therapy of uveitis in children. Int Ophthalmol Clin. 2008, 48: 131-152. 10.1097/IIO.0b013e31817d7107.CrossRefPubMed
5.
go back to reference Imrie FR, Dick AD: Biologics in the treatment of uveitis. Curr Opin Ophthalmol. 2007, 18: 481-486. 10.1097/ICU.0b013e3282f03d42.CrossRefPubMed Imrie FR, Dick AD: Biologics in the treatment of uveitis. Curr Opin Ophthalmol. 2007, 18: 481-486. 10.1097/ICU.0b013e3282f03d42.CrossRefPubMed
6.
go back to reference Saurenmann RK, Levin AV, Rose JB: Tumour necrosis factor alpha inhibitors in the treatment of childhood uveitis. Rheumatology. 2006, 45: 982-989. 10.1093/rheumatology/kel030.CrossRefPubMed Saurenmann RK, Levin AV, Rose JB: Tumour necrosis factor alpha inhibitors in the treatment of childhood uveitis. Rheumatology. 2006, 45: 982-989. 10.1093/rheumatology/kel030.CrossRefPubMed
7.
go back to reference Gallagher MJ, Quinones K, Cervantes-Castaneds RA, Yilmaz T, Foster CS: Biologic response modifier therapy for refractory childhood uveitis. Br J Ophthalmol. 2007, 91: 1341-1344. 10.1136/bjo.2007.124081.PubMedCentralCrossRefPubMed Gallagher MJ, Quinones K, Cervantes-Castaneds RA, Yilmaz T, Foster CS: Biologic response modifier therapy for refractory childhood uveitis. Br J Ophthalmol. 2007, 91: 1341-1344. 10.1136/bjo.2007.124081.PubMedCentralCrossRefPubMed
8.
go back to reference Rajaraman RT, Kimura Y, Li S, Haines K, Chu DS: Retrospective case review of pediatric patients with uveitis treated with infliximab. Ophthalmology. 2006, 113: 308-314. 10.1016/j.ophtha.2005.09.037.CrossRefPubMed Rajaraman RT, Kimura Y, Li S, Haines K, Chu DS: Retrospective case review of pediatric patients with uveitis treated with infliximab. Ophthalmology. 2006, 113: 308-314. 10.1016/j.ophtha.2005.09.037.CrossRefPubMed
9.
go back to reference Ardoin SP, Kredich D, Rabinovich E, Schanberg LE, Jaffe GJ: Infliximab to treat chronic non infectious uveitis in children: retrospective case series with long-term follow-up. Am J Ophthalmol. 2007, 144: 844-849. 10.1016/j.ajo.2007.08.018.PubMedCentralCrossRefPubMed Ardoin SP, Kredich D, Rabinovich E, Schanberg LE, Jaffe GJ: Infliximab to treat chronic non infectious uveitis in children: retrospective case series with long-term follow-up. Am J Ophthalmol. 2007, 144: 844-849. 10.1016/j.ajo.2007.08.018.PubMedCentralCrossRefPubMed
10.
go back to reference Suhler EB, Smith JR, Giles TR: Infliximab Therapy for Refractory Uveitis: 2-Year results of a Prospective Trial. Arch Ophthalmol. 2009, 127: 819-822.PubMed Suhler EB, Smith JR, Giles TR: Infliximab Therapy for Refractory Uveitis: 2-Year results of a Prospective Trial. Arch Ophthalmol. 2009, 127: 819-822.PubMed
11.
go back to reference Tynjälä P, Kotaniemi K, Lindahl P, Latva K, Aalto K, Honkanen V, Lahdenne P: Adalimumab in juvenile idiopathic arthritis-associated chronic anterior uveitis. Rheumatology. 2008, 47: 339-344.CrossRefPubMed Tynjälä P, Kotaniemi K, Lindahl P, Latva K, Aalto K, Honkanen V, Lahdenne P: Adalimumab in juvenile idiopathic arthritis-associated chronic anterior uveitis. Rheumatology. 2008, 47: 339-344.CrossRefPubMed
12.
go back to reference Tynjala P, Lindhal P, Honkanen V, Lahdenne P, Kotaniemi K: Infliximab and etanercept in the treatment of chronic uveitis associated with refractory juvenile idiopathic arthritis. Ann Rheum Dis. 2007, 66: 548-550.PubMedCentralCrossRefPubMed Tynjala P, Lindhal P, Honkanen V, Lahdenne P, Kotaniemi K: Infliximab and etanercept in the treatment of chronic uveitis associated with refractory juvenile idiopathic arthritis. Ann Rheum Dis. 2007, 66: 548-550.PubMedCentralCrossRefPubMed
13.
go back to reference Tugal-Tutkun I, Ayranci O, Kasapcopur O, Kir N: Retrospective analysis of children with uveitis treated with infliximab. J AAPOS. 2008, 12: 611-613. 10.1016/j.jaapos.2008.08.007.CrossRefPubMed Tugal-Tutkun I, Ayranci O, Kasapcopur O, Kir N: Retrospective analysis of children with uveitis treated with infliximab. J AAPOS. 2008, 12: 611-613. 10.1016/j.jaapos.2008.08.007.CrossRefPubMed
14.
go back to reference Kahn P, Weiss M, Imundo LF, Levy DM: Favourable response to high-dose infliximab for refractory childhood uveitis. Ophthalmology. 2006, 113: 860-864. 10.1016/j.ophtha.2006.01.005.CrossRefPubMed Kahn P, Weiss M, Imundo LF, Levy DM: Favourable response to high-dose infliximab for refractory childhood uveitis. Ophthalmology. 2006, 113: 860-864. 10.1016/j.ophtha.2006.01.005.CrossRefPubMed
16.
go back to reference Kaisu Kotaniemi K, Säilä H, Kautiainen H: Long-term efficacy of adalimumab in the treatment of uveitis associated with juvenile idiopathic arthritis. Clin Ophthalmol. 2011, 5: 1425-1429.PubMedCentralCrossRefPubMed Kaisu Kotaniemi K, Säilä H, Kautiainen H: Long-term efficacy of adalimumab in the treatment of uveitis associated with juvenile idiopathic arthritis. Clin Ophthalmol. 2011, 5: 1425-1429.PubMedCentralCrossRefPubMed
17.
go back to reference Simonini G, Taddio A, Cattalini M: Prevention of flare recurrences in childhood-refractory chronic uveitis: an open-label comparative study of adalimumab versus infliximab. Arthritis Care Res. 2011, 63: 612-618. 10.1002/acr.20404.CrossRef Simonini G, Taddio A, Cattalini M: Prevention of flare recurrences in childhood-refractory chronic uveitis: an open-label comparative study of adalimumab versus infliximab. Arthritis Care Res. 2011, 63: 612-618. 10.1002/acr.20404.CrossRef
18.
go back to reference Simonini G, Zannin ME, Caputo R: Loss of efficacy during long-term infliximab therapy for sight-threatening childhood uveitis. Rheumatology. 2008, 47: 1510-1514. 10.1093/rheumatology/ken298.CrossRefPubMed Simonini G, Zannin ME, Caputo R: Loss of efficacy during long-term infliximab therapy for sight-threatening childhood uveitis. Rheumatology. 2008, 47: 1510-1514. 10.1093/rheumatology/ken298.CrossRefPubMed
19.
go back to reference Jabs DA, Nussemblatt RB, Rosembaum JT, and the Standardization of Uveitis Nomenclature (SUN) Working Group: Standardization of uveitis nomenclature for reporting clinical data: results of the first international workshop. Am J Ophthalmol. 2005, 140: 509-516.CrossRefPubMed Jabs DA, Nussemblatt RB, Rosembaum JT, and the Standardization of Uveitis Nomenclature (SUN) Working Group: Standardization of uveitis nomenclature for reporting clinical data: results of the first international workshop. Am J Ophthalmol. 2005, 140: 509-516.CrossRefPubMed
20.
go back to reference Jabs DA: Improving the reporting of clinical case series. Am J Ophthalmol. 2005, 139: 900-905. 10.1016/j.ajo.2004.12.009.CrossRefPubMed Jabs DA: Improving the reporting of clinical case series. Am J Ophthalmol. 2005, 139: 900-905. 10.1016/j.ajo.2004.12.009.CrossRefPubMed
21.
go back to reference Erdfelder E, Faul F, Buchner A: GPower. A general power analysis program. Behav Res Meth Instrum Comput. 1996, 28: 1-11. 10.3758/BF03203630.CrossRef Erdfelder E, Faul F, Buchner A: GPower. A general power analysis program. Behav Res Meth Instrum Comput. 1996, 28: 1-11. 10.3758/BF03203630.CrossRef
22.
go back to reference Cohen J: Statistical power analysis for the behavioral sciences. 1988, Hillsdale, NJ: Lawrence Erlbaum Associates, 2 Cohen J: Statistical power analysis for the behavioral sciences. 1988, Hillsdale, NJ: Lawrence Erlbaum Associates, 2
23.
go back to reference Dhingra N, Morgan J, Dick AD: Switching biologic agents for uveitis. Eye. 2009, 23: 1868-1870. 10.1038/eye.2009.203.CrossRefPubMed Dhingra N, Morgan J, Dick AD: Switching biologic agents for uveitis. Eye. 2009, 23: 1868-1870. 10.1038/eye.2009.203.CrossRefPubMed
24.
25.
go back to reference Simonini G, De Libero C, Caputo R: Use of Abatacept for childhood refractory vision-threatening uveitis [abstract]. Arthritis Rheum. 2010, 62: s100- Simonini G, De Libero C, Caputo R: Use of Abatacept for childhood refractory vision-threatening uveitis [abstract]. Arthritis Rheum. 2010, 62: s100-
26.
go back to reference Zulian F, Balzarin M, Falcini F: Abatacept for severe anti-tumor necrosis factor alpha refractory juvenile idiopathic arthritis-related uveitis. Arthritis Care Res. 2010, 62: 821-825. 10.1002/acr.20115.CrossRef Zulian F, Balzarin M, Falcini F: Abatacept for severe anti-tumor necrosis factor alpha refractory juvenile idiopathic arthritis-related uveitis. Arthritis Care Res. 2010, 62: 821-825. 10.1002/acr.20115.CrossRef
27.
go back to reference Wendling D, Paccou P, Berthelot JM: New onset of uveitis during anti-tumor necrosis factor treatment for rheumatic diseases. Semin Arthritis Rheum. 2011, 41: 503-510. 10.1016/j.semarthrit.2011.05.005.CrossRefPubMed Wendling D, Paccou P, Berthelot JM: New onset of uveitis during anti-tumor necrosis factor treatment for rheumatic diseases. Semin Arthritis Rheum. 2011, 41: 503-510. 10.1016/j.semarthrit.2011.05.005.CrossRefPubMed
Metadata
Title
Superior efficacy of Adalimumab in treating childhood refractory chronic uveitis when used as first biologic modifier drug: Adalimumab as starting anti-TNF-α therapy in childhood chronic uveitis
Authors
Gabriele Simonini
Andrea Taddio
Marco Cattalini
Roberto Caputo
Cinzia de Libero
Fulvio Parentin
Ilaria Pagnini
Loredana Lepore
Rolando Cimaz
Publication date
01-12-2013
Publisher
BioMed Central
Published in
Pediatric Rheumatology / Issue 1/2013
Electronic ISSN: 1546-0096
DOI
https://doi.org/10.1186/1546-0096-11-16

Other articles of this Issue 1/2013

Pediatric Rheumatology 1/2013 Go to the issue