Recent progress has included an expansion of the tools that we use to prevent organ damage in patients with SLE. Belimumab has been available since 2011, but it has more recently been approved by the US Food and Drug Administration for use in patients with lupus nephritis (LN) who are receiving standard-of-care therapy, and the addition of belimumab is associated with improved renal outcomes. Further, voclosporin, a calcineurin inhibitor, was shown in the AURORA trials to improve outcomes when added to mycophenolate mofetil as background induction therapy in patients with LN. I think that these are very exciting developments in the treatment of LN. We also have a new biologic, anifrolumab, that has been approved for the treatment of general lupus. In the TULIP trials, we saw that anifrolumab plus traditional background therapy improved outcomes. 

At this year's CCR West, Ruth Ann Vleugels, MD, MPH, MBA, made a strong argument for aggressive treatment, not only in patients with life- or organ-threatening complications of SLE but also in patients with severe skin manifestations. While cutaneous manifestations are not necessarily life-threatening, they can be quite disfiguring and can greatly negatively impact a patient's quality of life. Dr Vleugels now considers using anifrolumab much earlier in the course of treatment for discoid lupus erythematosus, right after topical agents. She shared some images showing both the potential for serious scarring in discoid lupus erythematosus and some rather dramatic improvements with treatment. In my own clinical experience, I have seen similarly dramatic improvements in cutaneous lesions with anifrolumab treatment. So, again, the use of anifrolumab in this setting is an example of how we are shifting our paradigm. We are really starting to move toward trying to treat our patients earlier and/or more aggressively, with the goal of preventing long-term damage.

In another presentation at CCR West, Kenneth Kalunian, MD, discussed some of the clinical challenges that are associated with assessing musculoskeletal outcomes in patients with SLE. The difficulty with getting consistent results for musculoskeletal outcomes may have contributed to the disappointing results that were observed in some phase 3 clinical trials. This is because the Systemic Lupus Erythematosus Disease Activity Index does not necessarily accurately capture clinically significant improvements in all patients, particularly those with more severe disease who have many swollen/tender joints at baseline, and we do not want to be negating clinically significant improvements in those patients with our measurements. There are also differences between various specific joints that may not be accounted for in outcome measurements. In general, for example, elbow and knee joints tend to show more inconsistent responses to therapy than metacarpophalangeal joints. Thus, there is interest in the use of other markers, strategies, and modalities to assess affected joints. Imaging with ultrasound and magnetic resonance imaging, which can improve the detection of inflammation, is one of the areas of interest.

The presentations by Dr Kalunian and John Cush, MD, highlight the ongoing efforts to identify urinary and serum biomarkers in the assessment of LN. Since it is neither practical nor safe to obtain serial renal biopsies, there is a lot of interest in finding and standardizing both serum and urinary biomarkers for LN that are reflective of disease activity and long-term outcomes, in addition to following proteinuria. Ideally, in the future, we will find biomarkers that we can use to help guide therapy and to help us know whether patients are having an adequate response. Both of these presentations at CCR West also reflect the broad interest in the development of multiple novel agents, based on an increased understanding of the pathways that are involved in lupus. 

Prior to CCR West, promising results with telitacicept, a novel BlyS/APRIL dual inhibitor, had been reported from a phase 3 trial in China, so we hope to see similar efficacy in a worldwide study. Other potential therapies that are being investigated in patients with lupus include JAK inhibitors (eg, itacitinib and baricitinib), Bruton tyrosine kinase inhibitors (eg, elsubrutinib), and chimeric antigen receptor T-cell therapy. I think that there is optimism and excitement about many of these new approaches, so we will look forward to seeing the next phases of those studies.