Table 2 Biotherapies and small molecule inhibitors against secreted mediators or immune cells and their approval for rheumatoid arthritis and psoriatic arthritis

TNF

Etanercept

Fusion protein Fc IgG1-TNFR2

Decoy receptor

Nov 1998

Dec 2000

Jan 2002

Mar 2004

Infliximab

Chimeric mAb to TNF

Antagonist

Nov 1999

Sep 2001

May 2005

Jun 2006

Adalimumab

Humanized mAb to TNF

Jan 2003

Sep 2004

Oct 2005

Jun 2006

Golimumab

Human mAb to TNF

Apr 2009

Apr 2009

Oct 2017

Apr 2009

Certolizumab pegol

Pegylated Fab’ fragment of humanized mAb to TNF

May 2009

Sep 2009

Sep 2013

Jan 2014

IL-1

Anakinra

Recombinant human IL-1 receptor

Receptor antagonist

Nov 2001

Jun 2002

–

–

Canakinumab

Human mAb to IL-1β

Antagonist

–

–

–

–

Rilonacept

Fusion protein Fc IgG1 linked to ligand-binding domains of IL-1R1 and IL-1RAcP

CTLA-4

Abatacept

Fusion protein Fc IgG1-CTLA-4

Binds CD80 and CD86 on APCs; prevents co-stimulation of T cells

Dec 2005

Jun 2006

Jul 2017

Mar 2018

CD20

Rituximab

Chimeric mAb to CD20

Binds CD20 on B cells; triggers cell death

Feb 2006

Jun 2006

–

–

Ocrelizumab

Humanized mAb to CD20

–

–

–

–

Ofatunumab

Human mAb to CD20

–

–

–

–

Obinutuzumab

Humanized mAb to CD20 with a glycoengineered Fc

–

–

–

–

IL-6

Tocilizumab

Humanized mAb to IL-6 receptor

Receptor antagonist

Jan 2010

May 2010

–

–

Sarilumab

Human mAb to IL-6 receptor

May 2017

Feb 2017

–

–

IL-12, IL-23

Ustekinumab

Human mAb to IL-12 and IL-23 p40 subunit

Antagonist

–

–

Sep 2013

Jan 2014

IL-17

Secukinumab

Human mAb to IL-17A

Antagonist

–

–

Jan 2016

Apr 2016

Ixekizumab

Human mAb to IL-17A

–

–

Dec 2017

Jun 2018

Brodalumab

Human mAb to IL-17 receptor A

Receptor antagonist

–

–

–

–

Janus kinase 1–3

Tofacitinib

Small molecule

Intracellular inhibitor; blocks activity of cytokines (IL-2, -4, -6, -7, -9, -10, -12, -15, -21, -23, IFN-α, -β, -γ)

Nov 2012

Apr 2014

Dec 2017

Oct 2018