Preclinical discovery and development of adalimumab for the treatment of rheumatoid arthritis

ABSTRACT

Introduction: Rheumatoid arthritis (RA) is an autoimmune disease that is characterized by progressive joint disorders with significant pain and stiffness. In the past, RA was a difficult -to-treat ailment, but nowadays with the advent of biologics and better treatment strategies, disease remission is an achievable goal. Tumor necrosis factor α (TNFα) inhibitors were the first category of biologics to emerge with adalimumab being the first fully human TNFα.

Areas covered: the authors provide an overview of the historical events that led to the discovery of TNFα inhibitors and more specifically the drug adalimumab. Several key trials are presented regarding the safety of the drug as well as its successful journey, but there is also a narrative description of the drug’s future after patent expiration.

Expert opinion: Adalimumab is a fully human TNFα inhibitor with a fairly rapid onset of action. It has a generally good safety and efficacy profile. Clinicians must be aware of the possible side effects and treat them in a timely manner or discontinue the drug where appropriate. Due to the success of the bio-originator adalimumab, a multitude of biosimilars have emerged but not, thus far, for all of the indications of the bio-originator.

KEYWORDS:

• Adalimumab
• biosimilars
• DMARDs
• phage display technique
• TNFα inhibitors

Abbreviations

RA	=	rheumatoid arthritis
NSAIDs	=	non-steroidal anti-inflammatory drugs
cs	=	corticosteroids
csDMARDs	=	conventional synthetic disease-modifying anti-rheumatic drugs
bDMARDs	=	biologic disease-modifying anti-rheumatic drugs
tsDMARDs	=	targeted synthetic disease modifying anti-rheumatic drugs
TNFα	=	tumour necrosis factor alpha
mAbs	=	monoclonal antibodies
ADA	=	adalimumab
FDA	=	food and drug administration
ETN	=	etanercept
INF	=	infliximab
hTNF	=	human tumor necrosis factor
CHO	=	Chinese hamster ovary
EMA	=	European Medicines Agency
MTX	=	methotrexate
Sc	=	subcutaneous

Article highlights

• Rheumatoid Arthritis (RA) was once a difficult disease to treat

• The advent of TNFα inhibitors has revolutionized the treatment of RA

• The journey that led to the discovery of TNFα is fascinating one with the Nobel Prize being awarded on numerous occasions.

• Adalimumab (ADA) is the first fully human TNFα approved for the treatment of RA

• ADA is a safe and efficacious TNFα inhibitor for the treatment of RA

• Biosimilars of ADA have come to age, but prices need to go down for better patient access

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

One reviewer has received speaker and advisory fees, travel grants and research grants from AbbVie, Abbott, Pfizer, Janssen Pharmaceuticals, Roche, Bristol, Novartis, Novamed, Biopas-UCB, Sanofi, and Eli Lilly and Company. Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.

Additional information

Funding

This manuscript has not been funded.