Biological DMARDs

Biological DMARDs take the form of monoclonal antibodies (mAbs) and recombinant fusion proteins which modulate cytokine levels via mechanisms which inhibit T and B cell activation, or by directly inhibiting pro-inflammatory tumour necrosis factor alpha (TNFα). All cytokine modulators must be used under specialist supervision.

Examples currently employed for anti-rheumatic therapy include:

Abatacept, a recombinant protein fusing the extracellular domain of human cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) to the modified Fc portion of human immunoglobulin G1 (IgG1). CTLA-4 is essential for T-cell co-stimulation. Abatacept acts as a T cell activation inhibitor and reduces active inflammation. Prescribed for moderate to severe active RA in patients unresponsive to other DMARDs, including methotrexate or TNFα inhibitors.

Tocilizumab, an anti-IL-6 receptor mAb, normally prescribed alongside methotrexate for patients with moderate to severe active RA unresponsive to other DMARDs or TNF inhibitors. Tocilizumab can be used as a monotherapy in patients intolerant of methotrexate. Use in the UK is covered by NICE guidance NICE TA375 and NICE TA247.

Rituximab, an anti-CD20 mAb designed to target surface CD20 on B-lymphocytes and classified as an anti-lymphocyte mAb. Rituximab can be prescribed for patients with severe active RA, whose disease has not responded adequately to other DMARDs, including one or more TNF inhibitors. Can also be prescribed for patients intolerant of other DMARDs. All anti-lymphocyte mAbs should be delivered by an experienced expert with immediate access to full resuscitation facilities. Due to their mechanism of action, this group of biologics can predispose patients to severe infection. In the UK use of rituximab infusion for RA is covered by NICE guidance (NICE TA195).

TNFα inhibitors

Etanercept, is a dimeric recombinant protein fusing the TNF receptor 2 to the Fc region of the human IgG1 antibody. This acts to bind TNF, removing it from the circulation, thereby reducing its pro-inflammatory effect. Indicated for moderate to severe active RA (with or without methotrexate) with an inadequate response to other DMARDs (see NICE guidance TA195), methotrexate naive severe, active, and progressive RA, active and progressive psoriatic arthritis inadequately responsive to other DMARDs (see NICE guidance TA103) and severe ankylosing spondylitis inadequately responsive to conventional NSAID therapy. Delivered by subcutaneous injection.

Adalimumab has a similar indication profile to etanercept, but may also be used to treat severe axial spondyloarthritis with objective signs of inflammation and without radiographic evidence of ankylosing spondylitis, in patients with an inadequate response to, or intolerance to NSAIDs. Delivered by subcutaneous injection.

Certolizumab pegol has a similar indication profile to adalimumab. Delivered by subcutaneous injection.

Golimumab has a similar indication profile to etanercept. Delivered by subcutaneous injection.

Infliximab was the first anti-TNFα mAb to be authorised for clinical use. It is licensed for active RA (with methotrexate) in patients with inadequate response to other DMARDs, and for patients with severe, active, and progressive RA who have not been treated with methotrexate or other DMARDs. Ankylosing spondylitis with severe axial symptoms and inadequate response to conventional therapy, active and progressive psoriatic arthritis not responding to DMARD therapy, and plaque psoriasis can also be treated with infliximab. Delivered by intravenous infusion.