1. Failure of 2 standard DMARDs including MTX for 6 months DAS28 > 5.1 on 2 occasions 1 month apart TOLERANT MTX Choose most appropriate agent and if no clear indication for a specific agent then use the least expensive biologic as monotherapy: Certolizumab pegol (TA186) or Adalimumab (TA 130) or Etanercept (TA130) or Tocilizumab (APC December 2013 ACT-SURE, ADACTA) Continue Review 6 monthly Switch to alternative biologic with different mechanism of action: Adalimumab (TA195) Etanercept (TA195) Tocilizumab (APC December 2013 ACT-SURE, ADACTA) DAS28 improvement ≥ 1.2 at 6 months (where no response at 3 months consider 2nd line options) Choose most appropriate agent and if no clear indication for a specific agent then use the least expensive biologic: Certolizumab pegol + MTX (TA186) or Adalimumab + MTX (TA 130) or Etanercept + MTX (TA130) or Golimumab + MTX (TA225) or Infliximab + MTX (TA130) or Tocilizumab + MTX (TA247) or Abatacept + MTX (TA280) DAS28 improvement ≥ 1.2 at 6 months (where no response at 3 months consider 2nd line options) *Rituximab + MTX (TA195) Switch to alternative biologic with different mechanism of action: Adalimumab + MTX (TA195) Etanercept + MTX (TA195) Infliximab + MTX (TA195) Golimumab + MTX (TA225) Abatacept + MTX (TA195) Tocilizumab **+ MTX (TA247) **Note: Tocilizumab is the only available agent following rituximab failure (inadequate response) NO YES NOYES Continue Review 6 monthly Specific circumstances that may suggest the use of a specific agent: Etanercept: Potential risk of TB. Potential risk of serious infections (concurrent steroids, COPD, DM, CHF). Adalimumab: Extra articular features/co-existent conditions such as: uveitis (TA143), psoriasis (TA146), IBD (TA 187). Infliximab: Body weight < 60kg, (potential cost saving). Compliance issues/needle phobia. Severely impaired manual dexterity. Rheumatoid vasculitis. Golimumab: Consider if patient over 100kg (patient access to double dose). Needle Phobia/compliance issues (monthly dosing). Patient convenience (monthly dosing). Tocilizumab: Features of IL-6 mediated disease (high ESR/CRP, anaemia of chronic disease, high ferritin. Consider in monotherapy. Avoid if known diverticular disease. Abatacept: Consider if high risk of serious adverse events or injection site reactions to anti-TNFs. Certolizumab: Consider for women of child-bearing age contemplating pregnancy (BSR guidelines pending). *Rituximab: Consider 1 st line if SLE/CTD overlap, latent TB with C/I to chemoprophylaxis, treated solid malignancy within last 5 years, history of demyelination (EULAR/ACR recommendations). Rituximab with an alternative DMARD or as monotherapy may be considered in patients with co-existing ILD unable to take MTX (BSR and BHPR guidelines). NO YES If DAS28 >3.2 and ≥1 swollen joint consider Intolerant/adverse event within 6 months – consider alternative biologic drug Prepared by Consultant Rheumatology Team at Worcestershire Acute Hospitals NHS Trust Rituximab C/I (consider serological status), adverse event or failure? NO YES Failure at this stage of treatment constitutes the end of the commissioned biologics pathway