Adalimumab

One of five currently available anti-TNFα biologics, Adalimumab is a fully human recombinant IgG1κ monoclonal immunoglobulin which binds with high affinity and specificity to both soluble and cell-surface bound forms of TNFα. Adalimumab blocks the interaction of TNFα with the p55 and p75 surface TNF receptors. It does not bind lymphotoxin-a.

TNFα is a central mediator of inflammation that is involved in the induction and maintenance of numerous inflammatory disorders. Adalimumab modulates biological responses that are induced or regulated by TNFα, including changes in the levels of adhesion molecules responsible for leukocyte migration such as ELAM-1, VCAM-1 and ICAM-1. Adalimumab was the first fully human monoclonal antibody approved by the FDA for use in rheumatoid arthritis in 2002. It has subsequently received label indications for psoriatic arthritis (2005), ankylosing spondylitis (2006), Crohn's disease (2007), and plaque psoriasis (2008), children aged 2 and above with juvenile idiopathic arthritis (2008), ulcerative colitis (2012), pediatric Crohn's disease, aged 6 years and older (2014) and moderate to severe hidradenitis suppurativa (2015). Dosing schedules are typically 40 mg subcutaneously every two weeks for arthritic diseases. For Crohn’s Disease and Pediatric doses see: http://www.drugs.com/dosage/adalimumab.html

In long-term studies evaluating adalimumab for two common indications, adalimumab was demonstrated to be safe and effective in a 5-year study in patients with active rheumatoid arthritis and in a four-year study in patients with moderate to severe active ulcerative colitis in maintaining remission or controlling symptoms. An analysis of data extracted from 23,458 patients entered in multi-national clinical trials involving rheumatoid arthritis, juvenile idiopathic arthritis, ankylosing spondylitis, psoriatic arthritis, psoriasis and Crohn’s Disease, indicated that adalimumab was safe, but the expected increase in infections and lymphomas were reported.

Adverse reactions of adalimumab are similar to other TNF antagonists. The major concerns are infectious diseases such as TB, fungi, Legionella or hepatitis B reactivation; lymphomas; autoimmunity including demyelinating disease and lupus; allergic reactions; cytopenias; and congestive heart failure.

Adalimumab biosimilars, M 923 [Baxalta-Momenta], ABP 501(Amgen), GP2017 (Sandoz), BI695501 [Boehringer-Ingelheim] and SB5 (Samsung) are in clinical trials and may become available in the next several years.

Package Insert

1. Guidi L, Pugliese D, Armuzzi A. Update on the management of inflammatory bowel disease: specific role of adalimumab. Clin Exp Gastroenterol. 2011; 4:163-172.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=21904462



2. Diak P, Siegel J, La Grenade L, Choi L, Lemery S, McMahon A. Tumor necrosis factor alpha blockers and malignancy in children: forty-eight cases reported to the Food and Drug Administration. Arthritis Rheum. 2010 Aug; 62 (8): 2517-2524.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=20506368



3. Parakkal D, Sifuentes H, Semer R, Ehrenpreis ED. Hepatosplenic T-cell lymphoma in patients receiving TNF-alpha inhibitor therapy: expanding the groups at risk. Eur J Gastroenterol Hepatol. 2011 Nov; 23 (12):1150-1156.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=21941193



4. Menter A, Tyring SK, Gordon K, Kimball AB, Leonardi CL, Langley RG, et al. Adalimumab therapy for moderate to severe psoriasis: A randomized, controlled phase III trial. J Am Acad Dermatol. 2008 Jan; 58 (1):106-115.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=17936411



5. Lovell DJ, Ruperto N, Goodman S, Reiff A, Jung L, Jarosova K, et al. Adalimumab with or without methotrexate in juvenile rheumatoid arthritis. N Engl J Med. 2008 Aug 21; 359 (8): 810-820.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=18716298



6. 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 Jan; 48 (1): 35-45.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12528101

7. Burmester GR, Matucci-Cernic M, X. Mariette X et al. Safety and effectiveness of adalimumab in patients with rheumatoid arthritis over 5 years of therapy in phase-3 and postmarketing observational studies.  Arthritis Res Ther 2014:16 (1): R24.
http://www.ncbi.nlm.nih.gov/pubmed/24460746

8. 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 Aug 26. doi: 10.1038/ajg.2014.242.
http://www.ncbi.nlm.nih.gov/pubmed/25155227

9. Burmester GR, Panaccione R, Gordon KB et al.  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 – 524. http://ard.bmj.com/content/72/4/517.short

10. Downey C. Review Article. Serious infection during etanercept, infliximab and adalimumab therapy for rheumatoid arthritis: a literature review. Int. J. Rheum Dis.  2015. July. http://www.ncbi.nlm.nih.gov/pubmed/26200188

11. Neovius M, Arkema EV, Olsson H et al.  Drug survival on TNF inhibitors in patients with rheumatoid arthritis comparison of adalimumab, etanercept and infliximab. Ann. Rheum.Dis. 2015; 74:354-360. http://www.ncbi.nlm.nih.gov/pubmed/24285495

12. Dillingh MR¹, Reijers JA¹, Malone KE², Burggraaf J¹, Bahrt K³, Yamashita L³, Rehrig C³, Moerland M¹. Clinical Evaluation of Humira® Biosimilar ONS-3010 in Healthy Volunteers: Focus on Pharmacokinetics and Pharmacodynamics. Front Immunol. 2016; 7: 508.   https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5124695/

13. Minozzi S¹, Bonovas S², Lytras T^3,4,5, Pecoraro V⁶, González-Lorenzo M⁷, Bastiampillai AJ⁸, Gabrielli EM⁸, Lonati AC⁸, Moja L^6,7, Cinquini M⁹, Marino V¹⁰, Matucci A¹¹, Milano GM¹², Tocci G^13,14, Scarpa R¹⁵, Goletti D¹⁶, Cantini F¹⁷. Expert Opin Drug Saf. Risk of infections using anti-TNF agents in rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis: a systematic review and meta-analysis. 2016 Dec;15(sup1):11-34. https://www.ncbi.nlm.nih.gov/pubmed/27924643