Adalimumab (trade name Humira) is a a recombinant, fully human IgG1 monoclonal antibody and subcutaneously administered biological disease modifier which targets tumor necrosis factor (TNF). The drug is produced by recombinant DNA technology in a mammalian cell expression system and is purified by a process that includes specific viral inactivation and removal steps. Adalimumab is used to treat rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, Crohn's disease, ulcerative colitis, chronic psoriasis, hidradenitis suppurativa, juvenile idiopathic arthritis, and uveitis. It was originally launched by Abbvie in the US and approved in 2002 by the FDA. This drug is available in a prefilled syringe form and convenient pen form for subcutaneous self-administered doses. Adalimumab-adaz (Hyrimoz) is a new biosimilar to adalimumab developed by Novartis AG. It was approved by the FDA on October 31, 2008. However, due to the importance of TNF in host defense, one of the issues of major concern with all TNF-blockers, including adalimumab, is the increased risk of infections and malignancies.
Psoriasis is a chronic inflammatory immune-mediated skin disease that affects 1%-3% of general population. The disease is characterized by hyperproliferation and abnormal differentiation of keratinocytes, vascular changes in the papillary dermis, intraepidermal accumulation of neutrophils and dermal inflammation with prominent lymphocytic infiltrate. The development of psoriasis has a multifactorial nature resulting from the interaction between genetic predisposition and environmental factors. Pathogenic mechanisms are considered to be secondary to an abnormal immune response, with an aberrant regulation of both the adaptative (CD4+ Th1 lymphocytes and CD8+ type-1 T-cells) and the innate immunity (dendritic cells, macrophages, keratinocytes) resulting in a complex network of cytokines, chemokines and growth factors. The serendipitous discovery of the effectiveness of anti-TNF biologics in psoriasis has suggested the crucial role of this cytokine, which can be implicated in multiple events of psoriasis-related inflammation: attraction of leucocytes into the skin, activation of dendritic cells and T lymphocytes, release of epithelial and vascular growth factors, synthesis of cytokines, chemokines and other proinflammatory mediators via activation of NF-kappaB. The mechanism of action of adalimumab is primarily linked to the neutralization of TNF-alpha bioactivity by preventing the interaction of TNF-alpha with the cell surface TNF receptors. Through this mechanism, adalimumab inhibits several TNF-alpha-induced events, i.e., the release of serum cytokines (IL-6), acute phase reactants of inflammation, matrix metalloproteases and other markers of cartilage and synovium turnover, and the expression of adhesion molecules responsible for leukocyte migration. In addition, adalimumab lyses TNF-expressing cells in the presence of complement.
Fig 1. Mechanism of Action of Adalimumab
Table 1. Clinical Projects of Adalimumab*
NCT ID | Status | Conditions | Lead Sponsor | Update Time |
NCT03221621 | Recruiting | Hidradenitis Suppurativa | Erasmus Medical Center | July 18, 2017 |
NCT03816397 | Not yet recruiting | Uveitis, JIA | Nisha Acharya | January 25, 2019 |
NCT02904902 | Active, not recruiting | Hidradenitis Suppurativa | AbbVie | September 19, 2016 |
NCT03357939 | Active, not recruiting | Pharmacokinetics, Safety, Toleratiblity and Immunogenicity Comparison Between a Biosimilar and Humira in Healthy Volunteers | Shanghai Henlius Biotech | November 30, 2017 |
NCT03172377 | Recruiting | Crohn Disease in Remission, Crohn Disease | Radboud University | June 1, 2017 |
NCT02762955 | Active, not recruiting | Psoriasis | Biocad | May 5, 2016 |
NCT03849313 | Not yet recruiting | Healthy Volunteers | Alvotech Swiss AG | February 21, 2019 |
NCT03306446 | Recruiting | CD | Groupe d'Etude Therapeutique des Affections Inflammatoires Digestives | October 11, 2017 |
NCT02035800 | Recruiting | RheumatoId Arthritis | Université de Sherbrooke | January 14, 2014 |
NCT03828019 | Not yet recruiting | Uveitis | JHSPH Center for Clinical Trials | February 4, 2019 |
NCT01893996 | Active, not recruiting | Rheumatoid Arthritis, Cardiovascular Disease | University of California, San Francisco | July 9, 2013 |
NCT03311464 | Recruiting | Pyoderma Gangrenosum | AbbVie | October 17, 2017 |
NCT02808975 | Active, not recruiting | Hidradenitis Suppurativa (HS) | AbbVie | June 22, 2016 |
NCT03153319 | Recruiting | Mucopolysaccharidosis I, II | Los Angeles Biomedical Research Institute | May 15, 2017 |
NCT03607903 | Active, not recruiting | Pain, Injection Site | Centre for Human Drug Research, Netherlands | July 31, 2018 |
NCT02706704 | Recruiting | Uveitis, Non-Infectious Uveitis | American University of Beirut Medical Center | March 11, 2016 |
NCT02471118 | Recruiting | Osteoarthritis, Knee | Canadian Research & Education in Arthritis | June 15, 2015 |
NCT01716039 | Active, not recruiting | Ulcerative Colitis | University of Western Ontario, Canada | October 29, 2012 |
NCT02065557 | Recruiting | Ulcerative Colitis (UC) | AbbVie | February 19, 2014 |
NCT02632175 | Enrolling by invitation | Ulcerative Colitis (UC) | AbbVie | December 16, 2015 |
NCT03383263 | Recruiting | Polyarticular Juvenile Arthritis | AbbVie | December 26, 2017 |
NCT03823391 | Not yet recruiting | Rheumatoid Arthritis (RA) | AbbVie | January 30, 2019 |
NCT03561649 | Recruiting | Spondylitis, Ankylosing | University Hospital, Grenoble | June 19, 2018 |
NCT03017014 | Recruiting | Crohn's Disease | AbbVie | January 11, 2017 |
NCT03464136 | Recruiting | Crohn Disease | Janssen Scientific Affairs, LLC | March 13, 2018 |
NCT02332590 | Active, not recruiting | Rheumatoid Arthritis | Sanofi | January 7, 2015 |
NCT01848561 | Recruiting | Ulcerative Colitis (UC) | AbbVie | May 7, 2013 |
NCT03259074 | Recruiting | Ankylosing Spondylitis | Novartis Pharmaceuticals | August 23, 2017 |
NCT02745080 | Active, not recruiting | Psoriatic Arthritis | Novartis Pharmaceuticals | April 20, 2016 |
NCT02738125 | Active, not recruiting | Ulcerative Colitis (UC) | AbbVie | April 14, 2016 |
NCT03261102 | Recruiting | Crohn Disease, Drug Monitoring, Inflammatory Bowel Diseases | waqqas.afif | August 24, 2017 |
NCT03619876 | Not yet recruiting | Rheumatoid Arthritis, Myocardial Inflammation | Columbia University | August 8, 2018 |
NCT03505892 | Recruiting | Ankylosing Spondylitis (AS) | AbbVie | April 23, 2018 |
NCT03151551 | Active, not recruiting | Psoriatic Arthritis | Eli Lilly and Company | May 12, 2017 |
NCT02171429 | Recruiting | Ulcerative Colitis | Hoffmann-La Roche | June 24, 2014 |
NCT02163759 | Recruiting | Ulcerative Colitis | Hoffmann-La Roche | June 16, 2014 |
NCT03099083 | Active, not recruiting | Psoriasis | AbbVie | April 4, 2017 |
NCT03110094 | Recruiting | Rheumatoid Arthritis | Rennes University Hospital | April 12, 2017 |
NCT02916017 | Active, not recruiting | Uveitis | AbbVie | September 27, 2016 |
NCT03217734 | Recruiting | Psoriasis | Jeffrey J Crowley MD | July 14, 2017 |
NCT03789292 | Recruiting | Rheumatoid Arthritis | Celltrion | December 28, 2018 |
NCT02362074 | Recruiting | Rheumatoid Arthritis (RA) | AbbVie | February 12, 2015 |
NCT02988674 | Active, not recruiting | Spondylarthritis, Psoriatic Arthritis, Ankylosing Spondylitis (AS) | AbbVie | December 9, 2016 |
NCT02929251 | Recruiting | Uveitis, Biotherapy | Assistance Publique - Hôpitaux de Paris | October 11, 2016 |
NCT03505008 | Recruiting | Rheumatoid Arthritis | Keio University | April 20, 2018 |
NCT02687828 | Active, not recruiting | Intestinal Behcet's Disease (BD) | AbbVie | February 22, 2016 |
NCT02764762 | Recruiting | Crohn Disease | Takeda | May 6, 2016 |
NCT03001115 | Recruiting | Hidradenitis Suppurativa (HS) | AbbVie | December 22, 2016 |
NCT03339102 | Recruiting | Uveitis | AbbVie | November 13, 2017 |
NCT03849404 | Recruiting | Plaque Psoriasis | Alvotech Swiss AG | February 21, 2019 |
NCT02065570 | Active, not recruiting | Crohn's Disease | AbbVie | February 19, 2014 |
NCT03210259 | Recruiting | Psoriasis | Boehringer Ingelheim | July 6, 2017 |
NCT03155243 | Active, not recruiting | Uveitis | AbbVie | May 16, 2017 |
NCT02814175 | Recruiting | Psoriatic Arthritis | AbbVie | June 27, 2016 |
NCT02629159 | Active, not recruiting | Rheumatoid Arthritis | AbbVie | December 14, 2015 |
NCT03104400 | Recruiting | Psoriatic Arthritis | AbbVie | April 7, 2017 |
NCT03236870 | Recruiting | Psoriasis | AbbVie | August 2, 2017 |
NCT02130362 | Active, not recruiting | Crohn's Disease | AbbVie | May 5, 2014 |
NCT02878083 | Recruiting | ULCERATIVE COLITIS | Nantes University Hospital | August 25, 2016 |
NCT03389984 | Recruiting | Psoriasis Vulgaris | Poitiers University Hospital | January 4, 2018 |
NCT02506179 | Recruiting | Ulcerative Colitis (UC) | AbbVie | July 23, 2015 |
NCT02852694 | Recruiting | Crohn's Disease | PIBD-Net | August 2, 2016 |
NCT02087878 | Recruiting | Crohn's Disease, Ulcerative Colitis (UC), Hepatosplenic T-Cell Lymphoma | AbbVie | March 14, 2014 |
NCT02557100 | Active, not recruiting | Rheumatoid Arthritis | Bristol-Myers Squibb | September 23, 2015 |
NCT00783510 | Active, not recruiting | Juvenile Idiopathic Arthritis, JIA | AbbVie | October 31, 2008 |
NCT02896920 | Active, not recruiting | Hidradenitis Suppurativa (HS) | AbbVie | September 12, 2016 |
NCT02056184 | Active, not recruiting | Rheumatoid Arthritis, Targeted Ultrasound | University of Leeds | February 5, 2014 |
NCT03316781 | Recruiting | Plaque Psoriasis | Shanghai Henlius Biotech | October 20, 2017 |
NCT03180957 | Recruiting | Dupuytren's Disease | University of Oxford | June 8, 2017 |
NCT02871635 | Active, not recruiting | Crohn Disease | Boehringer Ingelheim | August 18, 2016 |
NCT03827876 | Recruiting | Psoriasis | Psoriasis Treatment Center of Central New Jersey | February 4, 2019 |
NCT02760407 | Recruiting | Rheumatoid Arthritis | R-Pharm | May 3, 2016 |
NCT03339089 | Recruiting | Ankylosing Spondylitis (AS), Psoriasis, Rheumatoid Arthritis (RA) | AbbVie | November 13, 2017 |
NCT02065622 | Active, not recruiting | Ulcerative Colitis (UC) | AbbVie | February 19, 2014 |
NCT02713295 | Active, not recruiting | Moderate to Severe Plaque Psoriasis | AbbVie | March 18, 2016 |
NCT03412747 | Active, not recruiting | Chronic Plaque Psoriasis, Moderate to Severe Plaque Psoriasis | UCB Biopharma S.P.R.L. | January 26, 2018 |
NCT02413047 | Recruiting | Inflammatory Bowel Disease, Ulcerative Colitis, Crohn's Disease | Indiana University | April 9, 2015 |
NCT02634060 | Recruiting | Crohn Disease, Colitis, Ulcerative | Universitaire Ziekenhuizen Leuven | December 17, 2015 |
NCT01077232 | Active, not recruiting | Psoriasis | AbbVie (prior sponsor, Abbott) | March 1, 2010 |
NCT01559038 | Active, not recruiting | Psoriatic Arthritis | AbbVie (prior sponsor, Abbott) | March 21, 2012 |
NCT02492217 | Recruiting | Ankylosing Spondylitis | Universidade Nova de Lisboa | July 8, 2015 |
NCT02896985 | Recruiting | Crohn's Disease | AbbVie | September 12, 2016 |
NCT03703817 | Recruiting | Rheumatoid Arthritis | Pfizer | October 12, 2018 |
NCT03248531 | Active, not recruiting | Hidradenitis Suppurativa | UCB Biopharma S.P.R.L. | August 14, 2017 |
NCT01387802 | Active, not recruiting | Ankylosing Spondylitis | AbbVie (prior sponsor, Abbott) | July 6, 2011 |
NCT02207244 | Active, not recruiting | Psoriasis | Janssen Research & Development, LLC | August 4, 2014 |
NCT00799877 | Active, not recruiting | Chronic Plaque Psoriasis | AbbVie (prior sponsor, Abbott) | December 1, 2008 |
NCT02207231 | Active, not recruiting | Psoriasis | Janssen Research & Development, LLC | August 4, 2014 |
NCT03220841 | Recruiting | Crohn Disease, Inflammatory Bowel Diseases, Stricture; Bowel | St Vincent's Hospital Melbourne | July 18, 2017 |
NCT03011268 | Recruiting | Colitis,Ulcerative | Helse Møre og Romsdal HF | January 5, 2017 |
NCT01698307 | Active, not recruiting | Crohn's Disease | University of Western Ontario, Canada | October 2, 2012 |
NCT02374021 | Recruiting | Arthritis, Rheumatoid | Brigham and Women's Hospital | February 27, 2015 |
NCT02456363 | Recruiting | Ankylosing Spondylitis | Chung Shan Medical University | May 28, 2015 |
NCT02856763 | Active, not recruiting | CD | Groupe d'Etude Therapeutique des Affections Inflammatoires Digestives | August 5, 2016 |
NCT02840175 | Recruiting | Juvenile Idiopathic Arthritis | Assistance Publique - Hôpitaux de Paris | July 21, 2016 |
NCT02092467 | Recruiting | Arthritis, Rheumatoid | Pfizer | March 20, 2014 |
NCT03352622 | Recruiting | Pharmacological Action | Universidad de Antioquia | November 24, 2017 |
NCT01602302 | Recruiting | Rheumatoid Arthritis | Medical University of Graz | May 18, 2012 |
NCT01706692 | Recruiting | Psoriasis | Swiss Dermatology Network for Targeted Therapies | October 15, 2012 |
NCT01793519 | Recruiting | Rheumatoid Arthritis | Georgetown University | February 15, 2013 |
NCT01965132 | Recruiting | Rheumatoid Arthritis, Ankylosing Spondylitis, Psoriatic Arthritis | Groupe d'Etude Therapeutique des Affections Inflammatoires Digestives | October 18, 2013 |
NCT03808506 | Not yet recruiting | Ulcerative Colitis | Assistance Publique - Hôpitaux de Paris | January 17, 2019 |
NCT03833271 | Recruiting | Juvenile Idiopathic Arthritis | Pfizer | February 6, 2019 |
NCT02889796 | Active, not recruiting | Rheumatoid Arthritis | Universidad de Antioquia | September 7, 2016 |
NCT02994836 | Recruiting | Crohn's Disease, Inflammatory Bowel Disease, Ulcerative Colitis | Medical University of Graz | December 16, 2016 |
NCT03737708 | Recruiting | Rheumatoid Arthritis (RA) | Swiss Dermatology Network for Targeted Therapies | November 9, 2018 |
NCT02134054 | Active, not recruiting | Inflammatory Bowel Disease | Georgetown University | May 8, 2014 |
NCT03445845 | Not yet recruiting | Axial Spondyloarthritis | Groupe d'Etude Therapeutique des Affections Inflammatoires Digestives | February 26, 2018 |
NCT03397108 | Recruiting | Crohn's Disease, Ulcerative Colitis, Healthy Controls | Assistance Publique - Hôpitaux de Paris | January 11, 2018 |
NCT02162472 | Recruiting | Psoriasis | Northwestern University | June 12, 2014 |
NCT02619552 | Active, not recruiting | Crohn's Disease, IBD | University of Maryland | December 2, 2015 |
NCT03759288 | Recruiting | Crohn's Disease, IBD | Allergan | November 29, 2018 |
NCT03100253 | Recruiting | Rheumatoid Arthritis | Mario Negri Institute for Pharmacological Research | April 4, 2017 |
NCT03853395 | Not yet recruiting | Arthritis, Rheumatoid, Psoriatic | University of Manchester | February 25, 2019 |
NCT03739853 | Not yet recruiting | Psoriatic Arthritis | University of Oxford | November 14, 2018 |
NCT01848028 | Recruiting | Psoriasis, Psoriatic-arthritis | Universitätsklinikum Hamburg-Eppendorf | May 7, 2013 |
NCT03108326 | Recruiting | Crohn Disease | Ced Service GmbH | April 11, 2017 |
NCT03016260 | Recruiting | RheumatoId Arthritis | TcLand Expression S.A. | January 10, 2017 |
NCT03056924 | Recruiting | Inflammatory Bowel Diseases | Boston Medical Center | February 17, 2017 |
NCT03679546 | Not yet recruiting | Ulcerative Colitis | Rennes University Hospital | September 20, 2018 |
NCT02878161 | Enrolling by invitation | Rheumatoid Arthritis | Fen Li | August 25, 2016 |
NCT03266471 | Enrolling by invitation | Inflammatory Bowel Diseases | Vanderbilt University Medical Center | August 30, 2017 |
NCT03847467 | Not yet recruiting | Inflammatory Bowel Diseases, Crohn Disease, Ulcerative Colitis | Children's Hospital Medical Center, Cincinnati | February 20, 2019 |
NCT03394586 | Recruiting | Ulcerative Colitis, Flare Up, Symptom | University of Zurich | January 9, 2018 |
NCT03712826 | Recruiting | Crohn Disease | Hospices Civils de Lyon | October 19, 2018 |
NCT02914717 | Active, not recruiting | Ulcerative Colitis | Universitaire Ziekenhuizen Leuven | September 26, 2016 |
NCT02075697 | Recruiting | Psoriasis | Fundación Academia Española de Dermatología | March 3, 2014 |
NCT03580876 | Recruiting | Clinical Failure After Switch | Védrines, Philippe, M.D. | July 9, 2018 |
NCT03839862 | Recruiting | Spondyloarthropathies, Ankylosing Spondylitis | Region Skane | February 15, 2019 |
NCT02674308 | Recruiting | Ulcerative Colitis and Crohn's Disease | Takeda | February 4, 2016 |
NCT01506661 | Active, not recruiting | Rheumatoid Arthritis, Varicella Zoster | Oklahoma Medical Research Foundation | January 10, 2012 |
NCT03219359 | Recruiting | Crohn Disease | Icahn School of Medicine at Mount Sinai | July 17, 2017 |
NCT00085995 | Recruiting | Spondylitis, Ankylosing | National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) | June 21, 2004 |
NCT02755194 | Recruiting | Lactation | The Hospital for Sick Children | April 28, 2016 |
NCT02714634 | Not yet recruiting | Rheumatoid Arthritis, Insufficient Response to Methotrexate. | University Hospital, Strasbourg, France | March 21, 2016 |
NCT03651518 | Not yet recruiting | Inflammatory Disease, Autoimmune Diseases | Assistance Publique - Hôpitaux de Paris | August 29, 2018 |
NCT02829424 | Recruiting | Psoriasis | Assistance Publique Hopitaux De Marseille | July 12, 2016 |
NCT03710486 | Recruiting | Ulcerative Colitis, Crohn's Disease | Takeda | October 18, 2018 |
NCT02242474 | Recruiting | Rheumatoid Arthritis | CHU de Quebec-Universite Laval | September 17, 2014 |
NCT02557308 | Recruiting | Ankylosing Spondylitis | Celltrion | September 23, 2015 |
NCT01764321 | Active, not recruiting | Rheumatoid Arthritis | UCB Pharma SA | January 9, 2013 |
NCT03775824 | Active, not recruiting | Rheumatoid Arthritis | Region Skane | December 14, 2018 |
NCT03681652 | Recruiting | Crohn Disease | Schneider Children's Medical Center, Israel | September 24, 2018 |
NCT03640637 | Not yet recruiting | Inflammatory Bowel Diseases, Crohn Disease, Ulcerative Colitis | Odense University Hospital | August 21, 2018 |
NCT02557295 | Recruiting | Rheumatoid Arthritis | Celltrion | September 23, 2015 |
NCT03591770 | Not yet recruiting | Inflammatory Bowel Diseases | Boston Medical Center | July 19, 2018 |
NCT00508547 | Recruiting | Psoriasis, Arthritis, Psoriatic | Janssen Scientific Affairs, LLC | July 30, 2007 |
NCT02353780 | Recruiting | Rheumatoid Arthritis (RA) | Dr. Larry W. Moreland | February 3, 2015 |
NCT03006809 | Recruiting | Ulcerative Colitis | Najwa Elnachef | December 30, 2016 |
Table 2. Approved Drugs of Adalimumab**
INN (trade name) | Therapeutic area | Dose | Strength | Route | Company | Marketing start | Market |
Humira | Rheumatoid Arthritis, Juvenile Idiopathic Arthritis, Psoriatic Arthritis, Ankylosing Spondylitis, Adult Crohn’s Disease, Pediatric Crohn’s Disease, Ulcerative Colitis, Plaque Psoriasis, Hidradenitis Suppurativa, Uveitis | Solution for injection | 40MG/0.8ML | Syringe | AbbVie | December 31, 2002 |
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Humira | plaque psoriasis, rheumatoid arthritis, axial spondyloarthritis , Crohn’s disease, ulcerative colitis, polyarticular juvenile idiopathic arthritis and active enthesitis-related arthritis, hidradenitis suppurativa, non-infectious uveitis | Solution for injection | 40MG/0.8ML | Syringe | AbbVie | September 8, 2003 |
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Reference
*The table was excerpted from the following website
https://clinicaltrials.gov/ct2/results?term=Adalimumab
**Information presented in the table were collected from the following website:
https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=125057
For research use only. Not intended for any clinical use.