The safety of anti-tumour necrosis factor treatments in rheumatoid arthritis: Meta and exposure-adjusted pooled analyses of serious adverse events

Annals of the Rheumatic Diseases

Volumn 68, Issue 7, 2009, Pages 1136-1145

  Leombruno, J P ^a   Einarson, T R ^a   Keystone, E C ^a  

^a UNIVERSITY OF TORONTO   (Canada)

Author keywords

[No Author keywords available]

Indexed keywords

ADALIMUMAB; DISEASE MODIFYING ANTIRHEUMATIC DRUG; ETANERCEPT; INFLIXIMAB; METHOTREXATE; SALAZOSULFAPYRIDINE; ANTIRHEUMATIC AGENT; TUMOR NECROSIS FACTOR ALPHA;

ARTICLE; BIOLOGICAL THERAPY; CLINICAL TRIAL; COCHRANE LIBRARY; DRUG MEGADOSE; DRUG SAFETY; EMBASE; HUMAN; INFECTION; INFECTION RISK; LOW DRUG DOSE; LYMPHOMA; MEDLINE; MELANOMA; META ANALYSIS; MORTALITY; NEOPLASM; PRIORITY JOURNAL; RECOMMENDED DRUG DOSE; RHEUMATOID ARTHRITIS; RISK ASSESSMENT; SKIN CANCER; SYSTEMATIC REVIEW; TREATMENT DURATION; UNSPECIFIED SIDE EFFECT; CHEMICALLY INDUCED DISORDER; DRUG ANTAGONISM; RANDOMIZED CONTROLLED TRIAL; REVIEW; RISK FACTOR;

ANTIRHEUMATIC AGENTS; ARTHRITIS, RHEUMATOID; HUMANS; INFECTION; NEOPLASMS; RANDOMIZED CONTROLLED TRIALS AS TOPIC; RISK FACTORS; TUMOR NECROSIS FACTOR-ALPHA;

EID: 67549117204     PISSN: 00034967     EISSN: 14682060     Source Type: Journal    
DOI: 10.1136/ard.2008.091025     Document Type: Article

References (64)

1. Wolfe F, Michaud K. Biologic treatment of rheumatoid arthritis and the risk of malignancy: analyses from a large US observational study. Arthritis Rheum 2007;56:2886-95.
2. Geborek P, Bladstrom A, Turesson C, Gulfe A, Petersson IF, Saxne T, et al. Tumour necrosis factor blockers do not increase overall tumour risk in patients with rheumatoid arthritis, but may be associated with an increased risk of lymphomas. Ann Rheum Dis 2005;64:699-703.
3. Dixon W, Silman A. Is there an association between anti-TNF monoclonal antibody therapy in rheumatoid arthritis and risk of malignancy and serious infection? Commentary on the meta-analysis by Bongartz et al. Arthritis Res Ther 2006;8:111.
4. Askling J, Fored CM, Brandt L, Baecklund E, Bertilsson L, Cöster L, et al. Risk and case characteristics of tuberculosis in rheumatoid arthritis associated with tumor necrosis factor antagonists in Sweden. Arthritis Rheum 2005;52:1986-92.
5. Askling J, Fored CM, Brandt L, Baecklund E, Brandt L, Ekbom A, et al. Risks of solid cancers in patients with rheumatoid arthritis and after treatment with tumour necrosis factor antagonists. Ann Rheum Dis 2005;64:1421-6.
6. Askling J. Malignancy and rheumatoid arthritis. Curr Rheumatol Rep 2007;9:421-6.
7. Lievre M, Cucherat M, Leizorovicz A. Pooling, meta-analysis, and the evaluation of drug safety. Curr Control Trials Cardiovasc Med 2002;3:6.
8. Altman DG, Deeks JJ. Meta-analysis, Simpson's paradox, and the number needed to treat. BMC Med Res Methodol 2002;2:3.
9. Jadad AR, Moore RA, Carroll D, Jenkinson C, Reynolds DJ, Gavaghan DJ, et al. Assessing the quality of reports of randomized clinical trials: is blinding necessary? Control Clin Trials 1996;17:1-12.
10. Humira (Adalimumab) product label. Abbott Laboratories. St Laurent, Quebec, Canada, 9 May 2007.
11. Enbrel (etanercept) product label. Amgen Canada. Mississauga, Ontario, Canada, 1 February 2007.
12. Remicade (infliximab) product label. Schering Plough Canada. Pointe Claire, Quebec, Canada, 12 June 2007.
13. Loke YK, Derry S. Reporting of adverse drug reactions in randomised controlled trials - a systematic survey. BMC Clin Pharmacol 2001;1:3.
14. Schmidt FL, Oh IS, Hayes TL. Fixed- versus random-effects models in meta-analysis: Model properties and an empirical comparison of differences in results. Br J Math Stat Psychol. Published Online First: 13 November 2007.
15. Mantel N, Haenszel W. Statistical aspects of the analysis of data from retrospective studies of disease. J Natl Cancer Inst 1959;22:719-48.
16. Robins J, Breslow N, Greenland S. Estimators of the Mantel-Haenszel variance consistent in both sparse data and large-strata limiting models. Biometrics 1986;42:311-23.
17. Bradburn MJ, Deeks JJ, Berlin JA, Russell LA. Much ado about nothing: a comparison of the performance of meta-analytical methods with rare events. Stat Med 2007;26:53-77.
18. Sweeting MJ, Sutton AJ, Lambert PC. What to add to nothing? Use and avoidance of continuity corrections in meta-analysis of sparse data. Stat Med 2004;23:1351-75.
19. Rituxan (rituximab) product label. Roche Canada. Mississauga, Ontario, Canada, 28 September 2007.
20. Orencia (abatacept) product label. Bristol-Myers Squibb Canada. Montreal, Quebec, Canada, 13 March 2007.
21. McEntegart DJ. Pooling in integrated safety databases. Drug Information J 2000;34:495-9.
22. Graham PL, Mengersen K, Morton AP. Confidence limits for the ratio of two rates based on likelihood scores: non-iterative method. Stat Med 2003;22:2071-83.
23. Klareskog L, van der Heijde D, de Jager JP, Gough A, Kalden J, Malaise M, et al. Therapeutic effect of the combination of etanercept and methotrexate compared with each treatment alone in patients with rheumatoid arthritis: double-blind randomised controlled trial. Lancet 2004;363:675-81.
24. Lipsky PE, van der Heijde DM, St Clair EW, Furst DE, Breedveld FC, Kalden JR, et al. Infliximab and methotrexate in the treatment of rheumatoid arthritis. Anti-Tumor Necrosis Factor Trial in Rheumatoid Arthritis with Concomitant Therapy Study Group. N Engl J Med 2000;343:1594- 602.
25. Maini RN, Breedveld FC, Kalden JR, Smolen JS, Davis D, Macfarlane JD, et al. Therapeutic efficacy of multiple intravenous infusions of anti-tumor necrosis factor alpha monoclonal antibody combined with low-dose weekly methotrexate in rheumatoid arthritis. Arthritis Rheum 1998;41:1552-63.
26. Moreland LW, Schiff MH, Baumgartner SW, Tindall EA, Fleischmann RM, Buloitt KJ, et al. Etanercept therapy in rheumatoid arthritis. A randomized, controlled trial. Ann Intern Med 1999;130:478-86.
27. van de Putte LB, Rau R, Breedveld FC, Kalden JR, Malaise MG, van Riel PL, et al. Efficacy and safety of the fully human anti-tumour necrosis factor alpha monoclonal antibody adalimumab (D2E7) in DMARD refractory patients with rheumatoid arthritis: a 12 week, phase II study. Ann Rheum Dis 2003;62:1168-77.
28. Weinblatt ME, Kremer JM, Bankhurst AD, Bulpitt JK, Fleischmann RM, Fox RI, et al. A trial of etanercept, a recombinant tumor necrosis factor receptor:Fc fusion protein, in patients with rheumatoid arthritis receiving methotrexate. N Engl J Med 1999;340:253-9.
29. Weisman MH, Paulus HE, Burch FX, Kivitz AJ, Fierer J, Dunn M, et al. A placebocontrolled, randomized, double-blinded study evaluating the safety of etanercept in patients with rheumatoid arthritis and concomitant comorbid diseases. Rheumatology (Oxford) 2007;46:1122-5.
30. Furst DE, Schiff MH, Fleischmann RM, Strand V, Birbara CA, Compagnone D, et al. Adalimumab, a fully human anti tumor necrosis factor-alpha monoclonal antibody, and concomitant standard antirheumatic therapy for the treatment of rheumatoid arthritis: results of STAR (Safety Trial of Adalimumab in Rheumatoid Arthritis). J Rheumatol 2003;30:2563-71.
31. Weinblatt ME, Keystone EC, Furst DE, Moreland LW, Weisman MH, Birbara CA, et al. Adalimumab, a fully human anti-tumor necrosis factor alpha monoclonal antibody, for the treatment of rheumatoid arthritis in patients taking concomitant methotrexate: the ARMADA trial. Arthritis Rheum 2003;48:35-45.
32. Keystone EC, Kavanaugh AF, Sharp JT, Tannenbaum H, Hua Y, Teoh LS, et al. Radiographic, clinical, and functional outcomes of treatment with adalimumab (a human anti-tumor necrosis factor monoclonal antibody) in patients with active rheumatoid arthritis receiving concomitant methotrexate therapy: a randomized, placebo-controlled, 52-week trial. Arthritis Rheum 2004;50:1400-11.
33. van de Putte LB, Atkins C, Malaise M, Sany J, Russell AS, van Riel PL, et al. Efficacy and safety of adalimumab as monotherapy in patients with rheumatoid arthritis for whom previous disease modifying antirheumatic drug treatment has failed. Ann Rheum Dis 2004;63:508-16.
34. Breedveld FC, Weisman MH, Kavanaugh AF, Cohen SB, Pavelka K, van Vollenhoven R, et al. The PREMIER study: a multicenter, randomized, double-blind clinical trial of combination therapy with adalimumab plus methotrexate versus methotrexate alone or adalimumab alone in patients with early, aggressive rheumatoid arthritis who had not had previous methotrexate treatment. Arthritis Rheum 2006;54:26-37.
35. Kremer JM, Weinblatt ME, Bankhurst AD, Bulpitt KJ, Fleischmann RM, Jackson CG, et al. Etanercept added to background methotrexate therapy in patients with rheumatoid arthritis: continued observations. Arthritis Rheum 2003;48:1493-9.
36. Genovese MC, Bathon JM, Martin RW, Fleischmann RM, Tesser JR, Schiff MH, et al. Etanercept versus methotrexate in patients with early rheumatoid arthritis: twoyear radiographic and clinical outcomes. Arthritis Rheum 2002;46:1443-50.
37. Bathon JM, Martin RW, Fleischmann RM, Tesser JR, Schiff MH, Keystone EC, et al. A comparison of etanercept and methotrexate in patients with early rheumatoid arthritis. N Engl J Med 2000;343:1586-93.
38. Keystone EC, Schiff MH, Kremer JM, Kafka S, Lovy M, DeVries T, et al. Once-weekly administration of 50 mg etanercept in patients with active rheumatoid arthritis: results of a multicenter, randomized, double-blind, placebo-controlled trial. Arthritis Rheum 2004;50:353-63.
39. van der Heidje D, Klareskog L, Rodriguez-Valverde V, Codreanu C, Bolosiu H, Melo-Gomes J, et al. Comparison of etanercept and methotrexate, alone and combined, in the treatment of rheumatoid arthritis: two-year clinical and radiographic results from the TEMPO study, a double-blind, randomized trial. Arthritis Rheum 2006;54:1063-74.
40. Combe B, Codreanu C, Fiocco U, Gaubitz M, Geusens PP, Kvien TK, et al. Etanercept and sulfasalazine, alone and combined, in patients with active rheumatoid arthritis despite receiving sulfasalazine: a double-blind comparison. Ann Rheum Dis 2006;65:1357-62.
41. Maini RN, Breedveld FC, Kalden JR, Smolen JS, Furst D, Weisman MH, et al. Sustained improvement over two years in physical function, structural damage, and signs and symptoms among patients with rheumatoid arthritis treated with infliximab and methotrexate. Arthritis Rheum 2004;50:1051-65.
42. Maini R, St Clair EW, Breedveld F, Furst D, Kalden J, Weisman M, et al. Infliximab (chimeric anti-tumour necrosis factor alpha monoclonal antibody) versus placebo in rheumatoid arthritis patients receiving concomitant methotrexate: a randomised phase III trial. ATTRACT Study Group. Lancet 1999;354:1932-9.
43. St Clair EW, van der Heijde DM, Smolen JS, Maini RN, Bathon JM, Emery P, et al. Combination of infliximab and methotrexate therapy for early rheumatoid arthritis: a randomized, controlled trial. Arthritis Rheum 2004;50:3432-43.
44. Abe T, Takeuchi T, Miyasaka N, Hashimoto H, Kondo H, Ichikawa Y, et al. A multicenter, double-blind, randomized, placebo controlled trial of infliximab combined with low dose methotrexate in Japanese patients with rheumatoid arthritis. J Rheumatol 2006;33:37-44.
45. Westhovens R, Yocum D, Han J, Berman A, Strusberg I, Geusens P, et al. The safety of infliximab, combined with background treatments, among patients with rheumatoid arthritis and various comorbidities: a large, randomized, placebocontrolled trial. Arthritis Rheum 2006;54:1075- 86.
46. Bax L, Yu LM, Ikeda N, Tsuruta H, Moons KG. Development and validation of MIX: comprehensive free software for meta-analysis of causal research data. BMC Med Res Methodol 2006;6:50.
47. Bongartz T, Sutton AJ, Sweeting MJ, Buchan I, Matteson EL, Montori V. Anti-TNF antibody therapy in rheumatoid arthritis and the risk of serious infections and malignancies: systematic review and meta-analysis of rare harmful effects in randomized controlled trials. JAMA 2006;295:2275-85.
48. Carmona L, Descalzo MA, Perez-Pampin E, Ruiz-Montesinos D, Erra A, Cobo T, et al. All-cause and cause-specific mortality in rheumatoid arthritis are not greater than expected when treated with tumour necrosis factor antagonists. Ann Rheum Dis 2007;66:880-5.
49. Jacobsson LT, Turesson C, Nilsson JA, Petersson IF, Lindgvist E, Saxne T, et al. Treatment with TNF blockers and mortality risk in patients with rheumatoid arthritis. Ann Rheum Dis 2007;66:670-5.
50. Wolfe F, Caplan L, Michaud K. Treatment for rheumatoid arthritis and the risk of hospitalization for pneumonia: associations with prednisone, disease-modifying antirheumatic drugs, and anti-tumor necrosis factor therapy. Arthritis Rheum 2006;54:628-34.
51. Dixon WG, Watson K, Lunt M, Hyrich KL, Silman AJ, Symmons DP. Rates of serious infection, including site-specific and bacterial intracellular infection, in rheumatoid arthritis patients receiving anti-tumor necrosis factor therapy: results from the British Society for Rheumatology Biologics Register. Arthritis Rheum 2006;54:2368-76.
52. Listing J, Strangfeld A, Kary S, Rau R, von Hinueber U, Stoyanova-Scholz M, et al. Infections in patients with rheumatoid arthritis treated with biologic agents. Arthritis Rheum 2005;52:3403-12.
53. Dixon WG, Symmons DP, Lunt M, Watson KD, Hyrich KL, Silman AJ. Serious infection following anti-tumor necrosis factor alpha therapy in patients with rheumatoid arthritis: lessons from interpreting data from observational studies. Arthritis Rheum 2007;56:2896-904.
54. Watson KD, Hyrich KL, Silman AJ, Symmons DPM. Anti-TNF therapy and mortality in rheumatoid arthritis patients registered with the British Society for Rheumatology Biologics Register (BSRBR). Annual European Congress on Rheumatology; 8-11 June 2005, Vienna, Austria: European League Against Rheumatism (EULAR) (Abstract no THU0273).
55. Leombruno JP, Einarson TR, Keystone E. Incidence and incidence density of death in controlled clinical trials of anti-TNF drugs in rheumatoid arthritis. Ann Rheum Dis 2005;64(Suppl III):464.
56. Scharf O, Colevas AD. Adverse event reporting in publications compared with sponsor database for cancer clinical trials. J Clin Oncol 2006;24:3933-8.
57. Falagas ME, Rosmarakis ES. Clinical decision-making based on findings presented in conference abstracts: is it safe for our patients? Eur Heart J 2006;27:2038-9.
58. Rosmarakis ES, Soteriades ES, Vergidis PI, Kasiakou SK, Falagas ME. From conference abstract to full paper: differences between data presented in conferences and journals. FASEB J 2005;19:673-80.
59. Kremer JM, Genant HK, Moreland LW, Russell AS, Emery P, Abud-Mendoza' C, et al. Effects of abatacept in patients with methotrexate-resistant active rheumatoid arthritis: a randomized trial. Ann Intern Med 2006;144(12):865-876.
60. Vishalpura TV, Grogg A, Abeyta K. Real-world dosing patterns for self administered anti-tumor necrosis factors. Academy of Managed Care Pharmacy's 18th Annual Meeting and Showcase; 5-8 April 2006, Seattle, Washington, 2006.
61. Ollendorf DA, Lidsky L, Zhao J. Patterns of dosing with adalimumab among commercially insured patients. Value in Health 2007;7:663.
62. Stern R, Wolfe F. Infliximab dose and clinical status: results of 2 studies in 1642 patients with rheumatoid arthritis. J Rheumatol 2004;31:1538-45.
63. Rahman MU, Strusberg I, Geusens P, Berman A, Yocum D, Baker D, et al. Double-blinded infliximab dose escalation in patients with rheumatoid arthritis. Ann Rheum Dis 2007;66:1233-8.
64. Johnsen AK, Schiff MH, Mease PJ, Moreland LW, Maier AL, Coblyn JS, et al. Comparison of 2 doses of etanercept (50 vs 100 mg) in active rheumatoid arthritis: a randomized double blind study. J Rheumatol 2006;33:659-64.