Two biologicals, belimumab and anifrolumab, are currently approved for use in SLE, and are therefore supported by extensive phase 3 clinical trials, while some others are supported by more limited data but may be used off-label. For the clinician an important practical question is which biological to choose for the individual in whom a biological is, indeed, needed to control the disease and achieve better outcomes.

Important considerations to guide such choices are:

• for belimumab, anti-DNA (+) status and low complement indicate a greater treatment effect

• for anifrolumab, specific benefits with respect to cutaneous manifestations of SLE have been demonstrated

• no other subsets of patients have been identified as particularly likely to respond to these two biologicals, but some subsets may be less likely to benefit

• belimumab is approved for both SLE in general and for lupus nephritis, and for use in pediatric patients

• the side effect profiles of belimumab and anifrolumab are dissimilar and may therefore guide treatment choice in individual cases

• the search for better biomarkers to guide therapy continues

• off-label biologicals such as rituximab and tocilizumab are supported by inconsistent data that leave important questions unanswered; they are most often used in a ‘back-against-the-wall’ situation.