16 Biologics: from RCTs to clinical practice

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The biologic medications anifrolumab and belimumab are currently approved for the treatment of systemic lupus erythematosus (SLE) in general, while the latter and obinutuzumab are approved specifically for the treatment of lupus nephritis. 1 Approval in each of these cases was supported by ample evidence from randomized clinical trials (RCTs) demonstrating efficacy and safety. However, such RCTs typically test narrowly defined hypotheses that leave many practical questions unanswered. For instance, practicing clinicians and their patients will wonder in which stage of the disease a biologic should be started, how it should be combined with other treatments, what follow-up assessments are most appropriate, and how to manage intercurrent events. Clinicians may wonder if the approval also applies to patients with more than one autoimmune diagnosis, or to patients with less severe lupus than was tested in the trials; and given the choice of at least two alternatives, how to choose among them. Moreover, as the number of approved biologicals (and targeted small-molecular agents) for lupus is likely to increase over the coming years, predicting the most likely successful treatment will become even more important.Fortunately, several data sources can help inform these decisions. Post-hoc analyses of clinical trial datasets have clarified key clinical issues but remain underutilized. While uncontrolled observational studies have enhanced our general understanding of biologic performance, more sophisticated methodologies—such as propensity score matching—now allow for robust conclusions from non-randomized data.2 Additionally, clinical trial emulation is emerging as a valuable tool, while large international studies are actively evaluating predictive biomarkers for treatment response. Synthesizing insights from these diverse methodologies will empower clinicians and patients to select the optimal treatment at the ideal time.Learning Objectives Describe currently approved biologics for SLE and/or lupus nephritis.Discuss the main trials supporting the approval of anifrolumab, belimumab and obinutuzumab.Explain the limitations of RCTs.Describe how non-randomized data can be employed to gain further understanding of biologics.Discuss perspective on current developments that will lead to better usage of biologics in clinical practice.References Kirou KA, Dall Era M, Aranow C, et al. Belimumab or anifrolumab for systemic lupus erythematosus? A risk-benefit assessment. Front Immunol. 2022;13:980079. doi: 10.3389/fimmu.2022.980079.Urowitz MB, Ohsfeldt RL, Wielage RC, et al. Organ damage in patients treated with belimumab versus standard of care: a propensity score-matched comparative analysis. Ann Rheum Dis. 2019;78(3):372–79. doi: 10.1136/annrheumdis-2018-214043.