Disease-modifying anti-rheumatic drugs

In DMARD-naïve patients, irrespective of the addition of glucocorticoids, conventional DMARD monotherapy or combination therapy of conventional DMARDs should be used

Rheumatologists should administer methotrexate (MTX) or combination therapy of MTX with other conventional synthetic DMARDs.

Among the DMARDs, MTX is considered the anchor drug and unless contraindicated, should be part of the first treatment strategy in patients at risk of persistent disease (2)

• in cases of MTX contraindications (or early intolerance), sulfasalazine or leflunomide should be considered as part of the (first) treatment strategy (1)

Azathioprine, cyclophosphamide and ciclosporin also have disease-modifying activity. However, they are usually reserved for people unresponsive to other DMARDs, due to the risk of serious adverse effects

There is some evidence showing the effectiveness of minocycline in RA. However, minocycline is not licensed for treating RA in the UK, and it is not used routinely

Leflunomide is a newer DMARD, which seems to be as effective as methotrexate or sulfasalazine at improving inflammation and function. However, its long-term effects are unclear
NICE guidelines on introducing and withdrawing DMARDs (3):

• for adults with newly diagnosed active RA:
  • offer first-line treatment with conventional disease-modifying anti-rheumatic drug (cDMARD) monotherapy using oral methotrexate, leflunomide or sulfasalazine as soon as possible and ideally within 3 months of onset of persistent symptoms.
  • consider hydroxychloroquine for first-line treatment as an alternative to oral methotrexate, leflunomide or sulfasalazine for mild or palindromic disease.
  • escalate dose as tolerated.
• consider short-term bridging treatment with glucocorticoids (oral, intramuscular or intra-articular) when starting a new cDMARD.
• inadequate response to conventional DMARDs, consider biological DMARDs (3)

In patients responding insufficiently to MTX and/or other conventional DMARD strategies, with or without glucocorticoids, biological DMARDs (TNF inhibitors, abatacept or tocilizumab, and, under certain circumstances, rituximab) should be commenced with MTX (1)

Note:

• there is evidence that very early treatment with infliximab in addition to methotrexate in early, poor-prognosis rheumatoid arthritis reduces magnetic resonance imaging evidence of synovitis and damage, with sustained benefit after infliximab withdrawal (1)

Reference:

1. Smolen JS et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2013 update. Ann Rheum Dis. 2014;73(3):492-509.
2. Combe B et al. 2016 update of the EULAR recommendations for the management of early arthritis. Ann Rheum Dis. 2017;76(6):948-959.
3. National Institute for Health and Care Excellence (NICE) 2018. Rheumatoid arthritis in adults: management