Figure 1.

(a) Decision tree for treatment selection following first-line anti-TNF therapy. (b) Treatment options following first-line anti-TNF therapy considering patient characteristics^a (supporting references can be found in Supplemental Appendix Figure 1).

ACPA, anti-citrullinated peptide antibodies; CV, cardiovascular; IMID, immune-mediated inflammatory diseases; MACE, major adverse cardiovascular event; VTE, venous thromboembolism.

^aFavoured option if to be used as monotherapy. EULAR guidelines favour IL-6 inhibitors or JAKi as monotherapy in patients who have an intolerance to csDMARDs.

^bPreferred order of anti-TNFs is certolizumab

pegol > etanercept > adalimumab > golimumab > infliximab (based on authors’ experience). The short half-life of JAKi means that a short time needs to elapse before contraception is discontinued, but does not imply that these agents are recommended during either pregnancy or lactation.

^cTNFi indicated for use in inflammatory bowel disease, ankylosing spondylitis, psoriasis and psoriatic arthritis. Rituximab indicated for use in rheumatoid arthritis, polyangiitis and pemphigus vulgaris.

^dAnti-TNFs not recommended if vasculitis associated with anti-TNF use, some reports of vascular complications or drug-induced lupus. IL-6Ri recommended if vasculitis is giant cell arteritis.

^eMonoclonal antibody anti-TNFs to treat uveitis.

^fContraindication for JAKi based on ORAL surveillance data for tofacitinib as compared with anti -TNF. The ORAL Surveillance study (NCT02092467) showed that in in highly selected patients with RA ⩾ 50 years of age and ⩾ 1 baseline CV risk factor, there was a numerical difference favouring anti-TNFs compared with tofacitinib in the incidence rates of MACE, VTE and malignancies. However, it is not known if this is a class effect of JAKi, and long-term trials and real-world evidence for tofacitinib have not produced similar signals. Treatment choice should be made through shared decision-making but at the moment patients with risk factors should not be given JAKi if at all possible.

^gHigher risk of VTE with JAKi if patient has risk factors for VTE, but risk may not be consistent across the class.

^hAnti-TNFs not recommended if heart failure occurred while on treatment.

ⁱAnti-TNFs increase the incidence of herpes zoster but usually not of clinical interest JAKi trials show an increased incidence although this seems less marked with filgotinib.

^jInfliximab is contraindicated for patients with latent tuberculosis. Routine clinical practice is to screen all patients for latent TB and provide prophylactic treatment.

^kAll bDMARDs and JAKi provide some risk of increased infection. IL-6 inhibitors have a potentially slightly higher risk than other treatments. It should be noted that some therapies offer the possibility of using them at reduced dosages, such as etanercept (25 mg/week) and baricitinib (2 mg/day). The potential for dose reduction should be considered as part of the treatment strategy.