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Advances in Therapy
Published in: Advances in Therapy 1/2020

Open Access 01-01-2020 | Lymphoma | Original Research

Long-Term Safety of Adalimumab in 29,967 Adult Patients From Global Clinical Trials Across Multiple Indications: An Updated Analysis

Authors: Gerd R. Burmester, Kenneth B. Gordon, James T. Rosenbaum, Dilek Arikan, Winnie L. Lau, Peigang Li, Freddy Faccin, Remo Panaccione

Published in: Advances in Therapy | Issue 1/2020

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Abstract

Introduction

The safety profile of adalimumab was previously reported in 23,458 patients across multiple indications. Here we report the long-term safety of adalimumab in adults with plaque psoriasis (Ps), hidradenitis suppurativa (HS), rheumatoid arthritis (RA), ankylosing spondylitis, psoriatic arthritis, non-radiographic axial spondyloarthritis, peripheral spondyloarthritis, Crohn’s disease (CD), ulcerative colitis (UC), and non-infectious uveitis (UV).

Methods

Safety data from 77 clinical trials were pooled. Safety assessments included adverse events (AEs) and serious AEs (SAEs) that occurred after the first study dose and within 70 days (5 half-lives) after the last study dose.

Results

A total of 29,967 patients were included, representing 56,916 patient-years (PY) of exposure. The most frequently reported SAE of interest was infection (3.7/100 PY) with highest incidences in CD, RA, UV, and UC (3.5/100 PY–6.9/100 PY); serious infections in Ps (1.8/100 PY) and HS (2.8/100 PY) were lower. The observed number of deaths was below what would be expected in an age- and sex-adjusted population for most adalimumab-treated patients (including Ps). Lack of real-life data and limited long-term data (> 5 years) for most patients are limitations of this analysis.

Conclusion

The safety profile of adalimumab was consistent with previous findings and no new safety signals were observed.
Literature
1.
Humira (adalimumab). Summary of product characteristics. Maidenhead: AbbVie; 2018.
2.
Humira (adalimumab). Full prescribing information. North Chicago: AbbVie; 2018.
3.
Burmester GR, Panaccione R, Gordon KB, McIlraith MJ, Lacerda AP. Adalimumab: long-term safety in 23 458 patients from global clinical trials in rheumatoid arthritis, juvenile idiopathic arthritis, ankylosing spondylitis, psoriatic arthritis, psoriasis and Crohn’s disease. Ann Rheum Dis. 2013;72:517–24.PubMedCrossRef
4.
Reich K, Mrowietz U, Radtke MA, et al. Drug safety of systemic treatments for psoriasis: results from The German Psoriasis Registry PsoBest. Arch Dermatol Res. 2015;307:875–83.PubMedPubMedCentralCrossRef
5.
Curtis JR, Jain A, Askling J, et al. A comparison of patient characteristics and outcomes in selected European and US rheumatoid arthritis registries. Semin Arthritis Rheum. 2010;40:2e1–14e1.CrossRef
6.
Cobo-Ibanez T, Descalzo MA, Loza-Santamaria E, Carmona L, Munoz-Fernandez S. Serious infections in patients with rheumatoid arthritis and other immune-mediated connective tissue diseases exposed to anti-TNF or rituximab: data from the Spanish registry BIOBADASER 2.0. Rheumatol Int. 2014;34:953–61.PubMedCrossRef
7.
Galloway JB, Hyrich KL, Mercer LK, et al. Anti-TNF therapy is associated with an increased risk of serious infections in patients with rheumatoid arthritis especially in the first 6 months of treatment: updated results from the British Society for Rheumatology Biologics Register with special emphasis on risks in the elderly. Rheumatology. 2011;50:124–31.PubMedCrossRef
8.
den Broeder A, van de Putte L, Rau R, et al. A single dose, placebo controlled study of the fully human anti-tumor necrosis factor-alpha antibody adalimumab (D2E7) in patients with rheumatoid arthritis. J Rheumatol. 2002;29:2288–98.
9.
van de Putte LB, Rau R, Breedveld FC, 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.PubMedPubMedCentralCrossRef
10.
Weinblatt ME, Keystone EC, Furst DE, et al. Adalimumab, a fully human anti–tumor necrosis factor α monoclonal antibody, for the treatment of rheumatoid arthritis in patients taking concomitant methotrexate: the ARMADA trial. Arthritis Rheum. 2003;48:35–45.PubMedCrossRef
11.
Rau R, Simianer S, van Riel PL, et al. Rapid alleviation of signs and symptoms of rheumatoid arthritis with intravenous or subcutaneous administration of adalimumab in combination with methotrexate. Scand J Rheumatol. 2004;33:145–53.PubMedCrossRef
12.
van de Putte LB, Atkins C, Malaise M, 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.PubMedPubMedCentralCrossRef
13.
Breedveld FC, Weisman MH, Kavanaugh AF, 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.PubMedCrossRef
14.
Keystone EC, Kavanaugh AF, Sharp JT, 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.PubMedCrossRef
15.
Furst DE, Kavanaugh A, Florentinus S, Kupper H, Karunaratne M, Birbara CA. Final 10-year effectiveness and safety results from study DE020: adalimumab treatment in patients with rheumatoid arthritis and an inadequate response to standard therapy. Rheumatology (Oxford). 2015;54:2188–97.
16.
Furst DE, Schiff MH, Fleischmann RM, 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.PubMed
17.
Burmester GR, Mariette X, Montecucco C, et al. Adalimumab alone and in combination with disease-modifying antirheumatic drugs for the treatment of rheumatoid arthritis in clinical practice: the Research in Active Rheumatoid Arthritis (ReAct) trial. Ann Rheum Dis. 2007;66:732–9.PubMedPubMedCentralCrossRef
18.
Bejarano V, Quinn M, Conaghan PG, et al. Effect of the early use of the anti-tumor necrosis factor adalimumab on the prevention of job loss in patients with early rheumatoid arthritis. Arthritis Rheum. 2008;59:1467–74.PubMedCrossRef
19.
van der Bijl AE, Breedveld FC, Antoni CE, et al. An open-label pilot study of the effectiveness of adalimumab in patients with rheumatoid arthritis and previous infliximab treatment: relationship to reasons for failure and anti-infliximab antibody status. Clin Rheumatol. 2008;27:1021–8.PubMedPubMedCentralCrossRef
20.
Chen DY, Chou SJ, Hsieh TY, et al. Randomized, double-blind, placebo-controlled, comparative study of human anti-TNF antibody adalimumab in combination with methotrexate and methotrexate alone in Taiwanese patients with active rheumatoid arthritis. J Formos Med Assoc. 2009;108:310–9.PubMedCrossRef
21.
Haraoui B, Cividino A, Stewart J, Guerette B, Keystone EC. Safety and effectiveness of adalimumab in a clinical setting that reflects Canadian standard of care for the treatment of rheumatoid arthritis (RA): results from the CanACT study. BMC Musculoskelet Disord. 2011;12:261.PubMedPubMedCentralCrossRef
22.
Miyasaka N, Change Study Investigators. Clinical investigation in highly disease-affected rheumatoid arthritis patients in Japan with adalimumab applying standard and general evaluation: the CHANGE study. Mod Rheumatol. 2008;18:252–62.PubMedPubMedCentralCrossRef
23.
Burmester GR, Matucci-Cerinic M, Mariette X, et al. Safety and effectiveness of adalimumab in patients with rheumatoid arthritis over 5 years of therapy in a phase 3b and subsequent postmarketing observational study. Arthritis Res Ther. 2014;16:R24.PubMedPubMedCentralCrossRef
24.
Huang F, Zhang FC, Bao CD, et al. Adalimumab plus methotrexate for the treatment of rheumatoid arthritis: a multi-center randomized, double-blind, placebo-controlled clinical study. Zhonghua Nei Ke Za Zhi. 2009;48:916–21.PubMed
25.
Kavanaugh A, Fleischmann RM, Emery P, et al. Clinical, functional and radiographic consequences of achieving stable low disease activity and remission with adalimumab plus methotrexate or methotrexate alone in early rheumatoid arthritis: 26-week results from the randomised, controlled OPTIMA study. Ann Rheum Dis. 2013;72:64–71.PubMedCrossRef
26.
Takeuchi T, Yamanaka H, Ishiguro N, et al. Adalimumab, a human anti-TNF monoclonal antibody, outcome study for the prevention of joint damage in Japanese patients with early rheumatoid arthritis: the HOPEFUL 1 study. Ann Rheum Dis. 2014;73:536–43.PubMedCrossRef
27.
Kaeley GS, Evangelisto AM, Nishio MJ, et al. Methotrexate dosage reduction upon adalimumab initiation: clinical and ultrasonographic outcomes from the randomized noninferiority MUSICA trial. J Rheumatol. 2016;43:1480–9.PubMedCrossRef
28.
Burmester GR, Kivitz AJ, Kupper H, et al. Efficacy and safety of ascending methotrexate dose in combination with adalimumab: the randomised CONCERTO trial. Ann Rheum Dis. 2015;74:1037–44.PubMedCrossRef
29.
Kivitz A, Cohen S, Dowd JE, et al. Clinical assessment of pain, tolerability, and preference of an autoinjection pen versus a prefilled syringe for patient self-administration of the fully human, monoclonal antibody adalimumab: the TOUCH trial. Clin Ther. 2006;28:1619–29.PubMedCrossRef
30.
Nash P, Vanhoof J, Hall S, et al. Randomized crossover comparison of injection site pain with 40 mg/0.4 or 0.8 mL formulations of adalimumab in patients with rheumatoid arthritis. Rheumatol Ther. 2016;3:257–70.PubMedPubMedCentralCrossRef
31.
Gordon KB, Langley RG, Leonardi C, et al. Clinical response to adalimumab treatment in patients with moderate to severe psoriasis: double-blind, randomized controlled trial and open-label extension study. J Am Acad Dermatol. 2006;55:598–606.PubMedCrossRef
32.
Gordon K, Blum R, Papp K, et al. Efficacy and safety of adalimumab treatment in patients with moderate to severe psoriasis: a double-blind, randomized clinical trial. Psoriasis Forum. 2007;13:4–11.CrossRef
33.
Larian A, Emer JJ, Gordon K, et al. Efficacy and safety of a second adalimumab treatment cycle in psoriasis patients who relapsed after adalimumab discontinuation or dosage reduction: a double-blind, randomized, placebo-controlled trial. Psoriasis Forum. 2011;17:88–96.CrossRef
34.
Menter A, Tyring SK, Gordon K, et al. Adalimumab therapy for moderate to severe psoriasis: a randomized, controlled phase III trial. J Am Acad Dermatol. 2008;58:106–15.PubMedCrossRef
35.
Gordon K, Papp K, Poulin Y, Gu Y, Rozzo S, Sasso EH. Long-term efficacy and safety of adalimumab in patients with moderate to severe psoriasis treated continuously over 3 years: results from an open-label extension study for patients from REVEAL. J Am Acad Dermatol. 2012;66:241–51.PubMedCrossRef
36.
Asahina A, Nakagawa H, Etoh T, Ohtsuki M, Adalimumab M04-688 Study Group. Adalimumab in Japanese patients with moderate to severe chronic plaque psoriasis: efficacy and safety results from a phase II/III randomized controlled study. J Dermatol. 2010;37:299–310.PubMedCrossRef
37.
Asahina A, Ohtsuki M, Etoh T, et al. Adalimumab treatment optimization for psoriasis: results of a long-term phase 2/3 Japanese study. J Dermatol. 2015;42:1042–52.PubMedCrossRef
38.
Saurat JH, Stingl G, Dubertret L, et al. Efficacy and safety results from the randomized controlled comparative study of adalimumab vs. methotrexate vs. placebo in patients with psoriasis (CHAMPION). Br J Dermatol. 2008;158:558–66.PubMedCrossRef
39.
Thaçi D, Ortonne JP, Chimenti S, et al. A phase IIIb, multicentre, randomized, double-blind, vehicle-controlled study of the efficacy and safety of adalimumab with and without calcipotriol/betamethasone topical treatment in patients with moderate to severe psoriasis: the BELIEVE study. Br J Dermatol. 2010;163:402–11.PubMedCrossRef
40.
Strober BE, Poulin Y, Kerdel FA, et al. Switching to adalimumab for psoriasis patients with a suboptimal response to etanercept, methotrexate, or phototherapy: efficacy and safety results from an open-label study. J Am Acad Dermatol. 2011;64:671–81.PubMedCrossRef
41.
Leonardi C, Langley RG, Papp K, et al. Adalimumab for treatment of moderate to severe chronic plaque psoriasis of the hands and feet: efficacy and safety results from REACH, a randomized, placebo-controlled, double-blind trial. Arch Dermatol. 2011;147:429–36.PubMedCrossRef
42.
Cai L, Gu J, Zheng J, et al. Efficacy and safety of adalimumab in Chinese patients with moderate-to-severe plaque psoriasis: results from a phase 3, randomized, placebo-controlled, double-blind study. J Eur Acad Dermatol Venereol. 2017;31:89–95.PubMedCrossRef
43.
Elewski BE, Okun MM, Papp K, et al. Adalimumab for nail psoriasis: efficacy and safety from the first 26 weeks of a phase 3, randomized, placebo-controlled trial. J Am Acad Dermatol. 2018;78(90–9):e1.
44.
Papp K, Ho V, Teixeira HD, Guerette B, Chen K, Lynde C. Efficacy and safety of adalimumab when added to inadequate therapy for the treatment of psoriasis: results of PRIDE, an open-label, multicentre, phase IIIb study. J Eur Acad Dermatol Venereol. 2012;26:1007–13.PubMedCrossRef
45.
Hanauer SB, Sandborn WJ, Rutgeerts P, et al. Human anti-tumor necrosis factor monoclonal antibody (adalimumab) in Crohn’s disease: the CLASSIC-I trial. Gastroenterology. 2006;130:323–33.PubMedCrossRef
46.
Colombel JF, Sandborn WJ, Rutgeerts P, et al. Adalimumab for maintenance of clinical response and remission in patients with Crohn’s disease: the CHARM trial. Gastroenterology. 2007;132:52–65.PubMedCrossRef
47.
Sandborn WJ, Hanauer SB, Rutgeerts P, et al. Adalimumab for maintenance treatment of Crohn’s disease: results of the CLASSIC II trial. Gut. 2007;56:1232–9.PubMedPubMedCentralCrossRef
48.
Panaccione R, Colombel JF, Sandborn WJ, et al. Adalimumab sustains clinical remission and overall clinical benefit after 2 years of therapy for Crohn’s disease. Aliment Pharmacol Ther. 2010;31:1296–309.PubMedCrossRef
49.
Sandborn WJ, Rutgeerts P, Enns R, et al. Adalimumab induction therapy for Crohn disease previously treated with infliximab: a randomized trial. Ann Intern Med. 2007;146:829–38.PubMedCrossRef
50.
Watanabe M, Hibi T, Lomax KG, et al. Adalimumab for the induction and maintenance of clinical remission in Japanese patients with Crohn’s disease. J Crohns Colitis. 2012;6:160–73.PubMedCrossRef
51.
Watanabe M, Hibi T, Mostafa NM, et al. Long-term safety and efficacy of adalimumab in Japanese patients with moderate to severe Crohn’s disease. J Crohns Colitis. 2014;8:1407–16.PubMedCrossRef
52.
Rutgeerts P, Van Assche G, Sandborn WJ, et al. Adalimumab induces and maintains mucosal healing in patients with Crohn’s disease: data from the EXTEND trial. Gastroenterology. 2012;142:1102–11.PubMedCrossRef
53.
Lichtiger S, Binion DG, Wolf DC, et al. The CHOICE trial: adalimumab demonstrates safety, fistula healing, improved quality of life and increased work productivity in patients with Crohn’s disease who failed prior infliximab therapy. Aliment Pharmacol Ther. 2010;32:1228–39.PubMedCrossRef
54.
Löfberg R, Louis EV, Reinisch W, et al. Adalimumab produces clinical remission and reduces extraintestinal manifestations in Crohn’s disease: results from CARE. Inflamm Bowel Dis. 2012;18:1–9.PubMedCrossRef
55.
Panaccione R, Loftus EV Jr, Binion D, et al. Efficacy and safety of adalimumab in Canadian patients with moderate to severe Crohn’s disease: results of the Adalimumab in Canadian SubjeCts with ModErate to Severe Crohn’s DiseaSe (ACCESS) trial. Can J Gastroenterol. 2011;25:419–25.PubMedPubMedCentralCrossRef
56.
Colombel JF, Panaccione R, Bossuyt P, et al. Effect of tight control management on Crohn’s disease (CALM): a multicentre, randomised, controlled phase 3 trial. Lancet. 2017;390:2779–89.PubMedCrossRef
57.
Wu KC, Ran ZH, Gao X, et al. Adalimumab induction and maintenance therapy achieve clinical remission and response in Chinese patients with Crohn’s disease. Intest Res. 2016;14:152–63.PubMedPubMedCentralCrossRef
58.
Lambert RG, Salonen D, Rahman P, et al. Adalimumab significantly reduces both spinal and sacroiliac joint inflammation in patients with ankylosing spondylitis: a multicenter, randomized, double-blind, placebo-controlled study. Arthritis Rheum. 2007;56:4005–14.PubMedCrossRef
59.
Dougados M, Luo MP, Maksymowych WP, et al. Evaluation of the patient acceptable symptom state as an outcome measure in patients with ankylosing spondylitis: data from a randomized controlled trial. Arthritis Rheum. 2008;59:553–60.PubMedCrossRef
60.
Rudwaleit M, Rodevand E, Holck P, et al. Adalimumab effectively reduces the rate of anterior uveitis flares in patients with active ankylosing spondylitis: results of a prospective open-label study. Ann Rheum Dis. 2009;68:696–701.PubMedCrossRef
61.
Kobayashi S, Harigai M, Mozaffarian N, et al. A multicenter, open-label, efficacy, pharmacokinetic, and safety study of adalimumab in Japanese patients with ankylosing spondylitis. Mod Rheumatol. 2012;22:589–97.PubMedCrossRef
62.
Huang F, Gu J, Zhu P, et al. Efficacy and safety of adalimumab in Chinese adults with active ankylosing spondylitis: results of a randomised, controlled trial. Ann Rheum Dis. 2014;73:587–94.PubMedCrossRef
63.
Reinisch W, Sandborn WJ, Hommes DW, et al. Adalimumab for induction of clinical remission in moderately to severely active ulcerative colitis: results of a randomised controlled trial. Gut. 2011;60:780–7.PubMedCrossRef
64.
Sandborn WJ, van Assche G, Reinisch W, et al. Adalimumab induces and maintains clinical remission in patients with moderate-to-severe ulcerative colitis. Gastroenterology. 2012;142(257–65):e1–3.
65.
Colombel JF, Sandborn WJ, Ghosh S, et al. Four-year maintenance treatment with adalimumab in patients with moderately to severely active ulcerative colitis: data from ULTRA 1, 2, and 3. Am J Gastroenterol. 2014;109:1771–80.PubMedPubMedCentralCrossRef
66.
Suzuki Y, Motoya S, Hanai H, et al. Efficacy and safety of adalimumab in Japanese patients with moderately to severely active ulcerative colitis. J Gastroenterol. 2014;49:283–94.PubMedCrossRef
67.
Travis S, Feagan BG, Peyrin-Biroulet L, et al. Effect of adalimumab on clinical outcomes and health-related quality of life among patients with ulcerative colitis in a clinical practice setting: results from InspirADA. J Crohns Colitis. 2017;11:1317–25.PubMedPubMedCentralCrossRef
68.
Kimball AB, Kerdel F, Adams D, et al. Adalimumab for the treatment of moderate to severe hidradenitis suppurativa: a parallel randomized trial. Ann Intern Med. 2012;157:846–55.PubMedCrossRef
69.
Kimball AB, Okun MM, Williams DA, et al. Two phase 3 trials of adalimumab for hidradenitis suppurativa. N Engl J Med. 2016;375:422–34.PubMedCrossRef
70.
Mease PJ, Gladman DD, Ritchlin CT, et al. Adalimumab for the treatment of patients with moderately to severely active psoriatic arthritis: results of a double-blind, randomized, placebo-controlled trial. Arthritis Rheum. 2005;52:3279–89.PubMedCrossRef
71.
Mease PJ, Ory P, Sharp JT, et al. Adalimumab for long-term treatment of psoriatic arthritis: 2-year data from the adalimumab effectiveness in psoriatic arthritis trial (ADEPT). Ann Rheum Dis. 2009;68:702–9.PubMedCrossRef
72.
Genovese MC, Mease PJ, Thomson GT, et al. Safety and efficacy of adalimumab in treatment of patients with psoriatic arthritis who had failed disease modifying antirheumatic drug therapy. J Rheumatol. 2007;34:1040–50.PubMed
73.
Rudwaleit M, Van den Bosch F, Kron M, Kary S, Kupper H. Effectiveness and safety of adalimumab in patients with ankylosing spondylitis or psoriatic arthritis and history of anti-tumor necrosis factor therapy. Arthritis Res Ther. 2010;12:R117.PubMedPubMedCentralCrossRef
74.
Jaffe GJ, Dick AD, Brezin AP, et al. Adalimumab in patients with active noninfectious uveitis. N Engl J Med. 2016;375:932–43.PubMedCrossRef
75.
Nguyen QD, Merrill PT, Jaffe GJ, et al. Adalimumab for prevention of uveitic flare in patients with inactive non-infectious uveitis controlled by corticosteroids (VISUAL II): a multicentre, double-masked, randomised, placebo-controlled phase 3 trial. Lancet. 2016;388:1183–92.PubMedCrossRef
76.
Suhler EB, Adan A, Brezin AP, et al. Safety and efficacy of adalimumab in patients with noninfectious uveitis in an ongoing open-label study: VISUAL III. Ophthalmology. 2018;125:1075–87.PubMedCrossRef
77.
Sieper J, van der Heijde D, Dougados M, et al. Efficacy and safety of adalimumab in patients with non-radiographic axial spondyloarthritis: results of a randomised placebo-controlled trial (ABILITY-1). Ann Rheum Dis. 2013;72:815–22.PubMedCrossRef
78.
Landewe R, Sieper J, Mease P, et al. Efficacy and safety of continuing versus withdrawing adalimumab therapy in maintaining remission in patients with non-radiographic axial spondyloarthritis (ABILITY-3): a multicentre, randomised, double-blind study. Lancet. 2018;392:134–44.PubMedCrossRef
79.
Mease P, Sieper J, Van den Bosch F, Rahman P, Karunaratne PM, Pangan AL. Randomized controlled trial of adalimumab in patients with nonpsoriatic peripheral spondyloarthritis. Arthritis Rheum. 2015;67:914–23.CrossRef
80.
Horneff G, Seyger MMB, Arikan D, et al. Safety of adalimumab in pediatric patients with polyarticular juvenile idiopathic arthritis, enthesitis-related arthritis, psoriasis, and Crohn’s disease. J Pediatr. 2018;201:166–75.PubMedCrossRef
81.
Scotto J, Fears TR, Fraumeni JF, National Cancer Institute (U.S.). Incidence of nonmelanoma skin cancer in the United States. Bethesda: U.S. Dept. of Health and Human Services, Public Health Service, National Institutes of Health, National Cancer Institute; 1983.
82.
Breslow NE, Day NE. Statistical methods in cancer research: volume II—the design and analysis of cohort studies. Lyon: International Agency for Research on Cancer; 1987.
83.
Burmester GR, Mease P, Dijkmans BAC, et al. Adalimumab safety and mortality rates from global clinical trials of six immune-mediated inflammatory diseases. Ann Rheum Dis. 2009;68:1863–9.PubMedCrossRef
84.
Atzeni F, Sarzi-Puttini P, Botsios C, et al. Long-term anti-TNF therapy and the risk of serious infections in a cohort of patients with rheumatoid arthritis: comparison of adalimumab, etanercept and infliximab in the GISEA registry. Autoimmun Rev. 2012;12:225–9.PubMedCrossRef
85.
Davila-Seijo P, Dauden E, Descalzo MA, et al. Infections in moderate to severe psoriasis patients treated with biological drugs compared to classic systemic drugs: findings from the BIOBADADERM registry. J Invest Dermatol. 2016;137:313–21.PubMedCrossRef
86.
Menter A, Thaci D, Wu JJ, et al. Long-term safety and effectiveness of adalimumab for moderate to severe psoriasis: results from 7-year interim analysis of the ESPRIT registry. Dermatol Ther (Heidelb). 2017;7:365–81.CrossRef
87.
van Dartel SA, Fransen J, Kievit W, et al. Difference in the risk of serious infections in patients with rheumatoid arthritis treated with adalimumab, infliximab and etanercept: results from the Dutch rheumatoid arthritis monitoring (DREAM) registry. Ann Rheum Dis. 2013;72:895–900.PubMedCrossRef
88.
Strangfeld A, Eveslage M, Schneider M, et al. Treatment benefit or survival of the fittest: what drives the time-dependent decrease in serious infection rates under TNF inhibition and what does this imply for the individual patient? Ann Rheum Dis. 2011;70:1914–20.PubMedCrossRef
89.
Doran MF, Crowson CS, Pond GR, O’Fallon WM, Gabriel SE. Predictors of infection in rheumatoid arthritis. Arthritis Rheum. 2002;46:2294–300.PubMedCrossRef
90.
Lichtenstein GR, Feagan BG, Cohen RD, et al. Serious infections and mortality in association with therapies for Crohn’s disease: TREAT registry. Clin Gastroenterol Hepatol. 2006;4:621–30.PubMedCrossRef
91.
Ali T, Kaitha S, Mahmood S, Ftesi A, Stone J, Bronze MS. Clinical use of anti-TNF therapy and increased risk of infections. Drug Healthc Patient Saf. 2013;5:79–99.PubMedPubMedCentralCrossRef
92.
Tubach F, Salmon D, Ravaud P, et al. Risk of tuberculosis is higher with anti-tumor necrosis factor monoclonal antibody therapy than with soluble tumor necrosis factor receptor therapy: the three-year prospective French Research Axed on Tolerance of Biotherapies registry. Arthritis Rheum. 2009;60:1884–94.PubMedPubMedCentralCrossRef
93.
Yonekura CL, Oliveira RDR, Titton DC, et al. Incidence of tuberculosis among patients with rheumatoid arthritis using TNF blockers in Brazil: data from the Brazilian Registry of Biological Therapies in Rheumatic Diseases (Registro Brasileiro de Monitoracao de Terapias Biologicas—BiobadaBrasil). Rev Bras Reumatol Engl Ed. 2017;57:477–83.PubMedCrossRef
94.
Cantini F, Niccoli L, Goletti D. Adalimumab, etanercept, infliximab, and the risk of tuberculosis: data from clinical trials, national registries, and postmarketing surveillance. J Rheumatol Suppl. 2014;91:47–55.PubMedCrossRef
95.
Salmon-Ceron D, Tubach F, Lortholary O, et al. Drug-specific risk of non-tuberculosis opportunistic infections in patients receiving anti-TNF therapy reported to the 3-year prospective French RATIO registry. Ann Rheum Dis. 2011;70:616–23.PubMedCrossRef
96.
Dixon WG, Hyrich KL, Watson KD, et al. Drug-specific risk of tuberculosis in patients with rheumatoid arthritis treated with anti-TNF therapy: results from the British Society for Rheumatology Biologics Register (BSRBR). Ann Rheum Dis. 2010;69:522–8.PubMedCrossRef
97.
Egeberg A, Skov L. Management of cardiovascular disease in patients with psoriasis. Expert Opin Pharmacother. 2016;17:1509–16.PubMedCrossRef
98.
Ljung L, Simard JF, Jacobsson L, Rantapaa-Dahlqvist S, Askling J, Anti-Rheumatic Therapy in Sweden Study Group. Treatment with tumor necrosis factor inhibitors and the risk of acute coronary syndromes in early rheumatoid arthritis. Arthritis Rheum. 2012;64:42–52.PubMedCrossRef
99.
Roubille C, Richer V, Starnino T, et al. The effects of tumour necrosis factor inhibitors, methotrexate, non-steroidal anti-inflammatory drugs and corticosteroids on cardiovascular events in rheumatoid arthritis, psoriasis and psoriatic arthritis: a systematic review and meta-analysis. Ann Rheum Dis. 2015;74:480–9.PubMedCrossRef
100.
Wu JJ, Guerin A, Sundaram M, Dea K, Cloutier M, Mulani P. Cardiovascular event risk assessment in psoriasis patients treated with tumor necrosis factor-alpha inhibitors versus methotrexate. J Am Acad Dermatol. 2017;76:81–90.PubMedCrossRef
101.
Strangfeld A, Hierse F, Rau R, et al. Risk of incident or recurrent malignancies among patients with rheumatoid arthritis exposed to biologic therapy in the German biologics register RABBIT. Arthritis Res Ther. 2010;12:R5.PubMedPubMedCentralCrossRef
102.
Askling J, van Vollenhoven RF, Granath F, et al. Cancer risk in patients with rheumatoid arthritis treated with anti-tumor necrosis factor alpha therapies: does the risk change with the time since start of treatment? Arthritis Rheum. 2009;60:3180–9.PubMedCrossRef
103.
Askling J, Baecklund E, Granath F, et al. Anti-tumour necrosis factor therapy in rheumatoid arthritis and risk of malignant lymphomas: relative risks and time trends in the Swedish Biologics Register. Ann Rheum Dis. 2009;68:648–53.PubMedCrossRef
104.
Hellgren K, Smedby KE, Feltelius N, Baecklund E, Askling J. Do rheumatoid arthritis and lymphoma share risk factors?: a comparison of lymphoma and cancer risks before and after diagnosis of rheumatoid arthritis. Arthritis Rheum. 2010;62:1252–8.PubMedCrossRef
105.
Long MD, Herfarth HH, Pipkin CA, Porter CQ, Sandler RS, Kappelman MD. Increased risk for non-melanoma skin cancer in patients with inflammatory bowel disease. Clin Gastroenterol Hepatol. 2010;8:268–74.PubMedPubMedCentralCrossRef
106.
Stern RS, Liebman EJ, Vakeva L. Oral psoralen and ultraviolet-A light (PUVA) treatment of psoriasis and persistent risk of nonmelanoma skin cancer. PUVA Follow-up Study. J Natl Cancer Inst. 1998;90:1278–84.PubMedCrossRef
107.
Baecklund E, Iliadou A, Askling J, et al. Association of chronic inflammation, not its treatment, with increased lymphoma risk in rheumatoid arthritis. Arthritis Rheum. 2006;54:692–701.PubMedCrossRef
108.
Chakravarty EF, Michaud K, Wolfe F. Skin cancer, rheumatoid arthritis, and tumor necrosis factor inhibitors. J Rheumatol. 2005;32:2130–5.PubMed
109.
Siegel CA, Marden SM, Persing SM, Larson RJ, Sands BE. Risk of lymphoma associated with combination anti-tumor necrosis factor and immunomodulator therapy for the treatment of Crohn’s disease: a meta-analysis. Clin Gastroenterol Hepatol. 2009;7:874–81.PubMedPubMedCentralCrossRef
110.
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.PubMedCrossRef
111.
Mercer LK, Regierer AC, Mariette X, et al. Spectrum of lymphomas across different drug treatment groups in rheumatoid arthritis: a European registries collaborative project. Ann Rheum Dis. 2017;76:2025–30.PubMedCrossRef
112.
Hellgren K, Smedby KE, Backlin C, et al. Ankylosing spondylitis, psoriatic arthritis, and risk of malignant lymphoma: a cohort study based on nationwide prospectively recorded data from Sweden. Arthritis Rheumatol. 2014;66:1282–90.PubMedCrossRef
113.
Sattar N, McCarey DW, Capell H, McInnes IB. Explaining how “high-grade” systemic inflammation accelerates vascular risk in rheumatoid arthritis. Circulation. 2003;108:2957–63.PubMedCrossRef
114.
Ridker PM, Everett BM, Thuren T, et al. Antiinflammatory therapy with canakinumab for atherosclerotic disease. N Engl J Med. 2017;377:1119–31.PubMedCrossRef
115.
Burmester GR, Landewe R, Genovese MC, et al. Adalimumab long-term safety: infections, vaccination response and pregnancy outcomes in patients with rheumatoid arthritis. Ann Rheum Dis. 2017;76:414–7.PubMedCrossRef
116.
Leonardi C, Papp K, Strober B, et al. The long-term safety of adalimumab treatment in moderate to severe psoriasis: a comprehensive analysis of all adalimumab exposure in all clinical trials. Am J Clin Dermatol. 2011;12:321–37.PubMedCrossRef
Metadata
Title
Long-Term Safety of Adalimumab in 29,967 Adult Patients From Global Clinical Trials Across Multiple Indications: An Updated Analysis
Authors
Gerd R. Burmester
Kenneth B. Gordon
James T. Rosenbaum
Dilek Arikan
Winnie L. Lau
Peigang Li
Freddy Faccin
Remo Panaccione
Publication date
01-01-2020

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