Congress highlights

Join Professor Antonis Fanouriakis share the latest highlights from EULAR 2022

Get the latest on managing systemic lupus nephritis in these video interviews with expert Professor Antonis Fanouriakis, following on from the 2022 European League Against Rheumatism Annual European Congress of Rheumatology. And read further for top highlights from the congress.

Join Professor Antonis Fanouriakis in this series of videos to hear about important topics relating to management of lupus that were discussed at the EULAR 2022 congress, including:

• Treat-to-target and disease modification approaches to managing lupus
• Cutting-edge research on tyrosine kinase 2 (TYK2) inhibitors and chimeric antigen receptor (CAR)-T cell therapy for systemic lupus nephritis (SLE)
• The latest data on treatment of lupus nephritis

The EULAR 2022 congress holds special significance as this year marks 75 years since the foundation of the association. The congress was held in Copenhagen, the city where EULAR was first formed in 1947 as the European section of the International League Against Rheumatism (ILAR), the global umbrella organisation for rheumatology¹. As an additional milestone, 2022 saw the first ever hybrid EULAR congress, where delegates could opt for in-person or virtual attendance. 

Here we zoom in on key presentations and discussions at EULAR 2022 that related to SLE and lupus nephritis, summarising important topics, late-breaking abstracts and cutting-edge research on these conditions.

Common themes at EULAR 2022

Disease modification and the treat-to-target approach, two important concepts that underpin the management of lupus, were common themes in many of the presentations and discussions at EULAR 2022.

Disease modification

Therapeutic intervention to alter the natural course of a disease is a well-established concept in rheumatology, having been introduced with the development of disease-modifying drugs for rheumatoid arthritis². To date, however, an accepted definition of disease modification for lupus is lacking. Establishing an accepted definition is important for assessing the ability of a drug to alter the natural course of the disease² and this topic remains an underlying theme of discussions relating to management of lupus.

Treat-to-target

Treat-to-target is a therapeutic approach consisting of three parts: first, identity an appropriate treatment target, ideally complete remission or, for most patients, the lowest possible level of disease activity with minimal exposure to glucocorticoids; second, take therapeutic steps to achieve the treatment target; third, closely monitor the outcome and adjust treatment as necessary^3,4.

The first clinical trial is in preparation to systematically assess the effectiveness of a treat-to-target approach for SLE⁵. As involvement of patients is vital in determining the success of this approach, Johanna Mucke and colleagues from Germany, Bulgaria and The Netherlands conducted a survey to investigate patients’ attitudes, needs and willingness to participate in treat-to-target studies⁶. Their findings, presented at EULAR 2022, confirmed that patients consider treat-to-target an important area of study and most would be willing to participate in clinical trials. For patients, the three most important treatment goals are normalisation of quality of life, prevention of organ damage and absence of disease activity⁶.

Late-breaking abstracts at EULAR 2022

Eric Morand and colleagues from Melbourne, Australia, submitted late-breaking abstracts describing results of the phase 2 PAISLEY study for deucravacitinib⁷ and two phase 3 studies, SLE-BRAVE-I and SLE-BRAVE-II, for baracitinib⁸. Georg Schett and colleagues also submitted an abstract on a preliminary study to assess a new technology for treatment of SLE.

Phase 2 PAISLEY study

PAISLEY was a 48-week, double-blind, placebo-controlled phase 2 trial to evaluate the oral, selective tyrosine kinase 2 (TYK2) inhibitor deucravacitinib. The trial recruited 363 patients with severe SLE, defined as seropositive with a Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score of ≥6 and ≥1 British Isles Lupus Assessment Group (BILAG) index A or ≥2 BILAG B manifestations. Patients were randomised to one of three dose regimens of deucravacitinib (3 or 6 mg twice daily or 12 mg once daily) or placebo twice daily. The study met the primary endpoint of SLE Responder Index (SRI) 4 at week 32, which was achieved in a significantly greater proportion of patients who received twice daily doses of 3 mg (58.2%, P=0.0006) or 6 mg (49.5%, P=0.02) deucravacitinib, compared with those who received placebo (34.4%). Deucravacitinib was well tolerated and SRI4 responses were sustained at week 48. No difference was seen between the high dose group (12 mg once daily) and placebo⁷. Deucravacitinib is currently under review by the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for treatment of plaque psoriasis⁹. The PAISLEY study shows that it warrants further investigation as a possible new treatment for SLE.

SLE-BRAVE-I and SLE-BRAVE-II

Baricitinib, an inhibitor of Janus kinase (JAK) 1 and 2, is approved in Europe for treatment of rheumatoid arthritis and atopic dermatitis¹⁰. Following a 24-week phase 2 trial showing that baricitinib improved disease activity in patients with SLE, this agent progressed to the phase 3 trials SLE-BRAVE-I and SLE-BRAVE-II. Both were 52-week, double-blind, randomised, placebo-controlled phase trials, identically designed, but with discordant results. In SLE-BRAVE-I baricitinib significantly reduced disease activity, while in SLE-BRAVE-II no difference was seen between treatment and control groups⁸. The efficacy of baricitinib in SLE, therefore, remains inconclusive.

CAR-T therapy: a new and promising technology for SLE

Georg Schett and colleagues from Germany presented results of their preliminary study to test a new technology in patients with severe refractory SLE¹¹. This technology involves the use of chimeric antigen receptor (CAR) T cells, genetically modified to recognise CD19 and other B cell surface antigens thought to play a role in the pathogenesis of SLE. Four patients with active SLE, including kidney disease, in whom standard treatment had failed, received CD19 CAR-T therapy. At 6 months follow-up, patient 1 had achieved drug-free remission (SLEDAI-2K = 0), and loss of antinuclear antibodies (ANAs) and double-stranded (ds) DNA. Patient 2, followed up at 2 months, also showed loss of ANAs and dsDNA. Patients 3 and 4 achieved SLEDAI-2K of 0, but their follow-up was shorter. All patients achieved a low lupus disease activity state (LLADS)¹¹. The therapy was well tolerated and may offer a solution for patients with refractory SLE.

Updates on treatment of lupus nephritis

Post hoc analysis of AURA LV and AURORA 1 trials for voclosporin

In 2021, the calcineurin inhibitor voclosporin was approved for the treatment of lupus nephritis following favourable outcomes at 24 weeks in the phase 2 AURA LV study and at 52 weeks in the phase 3 AURORA 1 study. Han-Joachim Anders and colleagues conducted a post hoc analysis of pooled data at 48 and 52 weeks in the AURA LV and AURORA studies, respectively. Compared with the control group, a greater proportion of patients who received voclosporin treatment achieved predefined targets of urine protein-to-creatine ratio (UPCR) at 3, 6 and 12 months, and a reduction in steroid dose to ≤7.5 mg/day.¹² These UPCR targets are consistent with EULAR and the European Renal Association (ERA) updated recommendations for targeted reductions in proteinuria¹³.

AURORA 2 trial for voclosporin

Amit Saxena presented results of the AURORA-2 trial, a 2-year continuation of AURORA-1¹⁴. Reassuringly, voclosporin, on a background of mycophenylate mofetil and low-dose steroid, was well tolerated, with no increase in adverse effects over 3 years, and reductions in UPCR were maintained.

References

1. Kvien TK. EULAR 75-year anniversary: commentaries on key ARD papers from 1947. Ann Rheum Dis. 2022;81(6):751.
2. van Vollenhoven R, Askanase AD, Bomback AS, Bruce IN, Carroll A, Dall'Era M, et al. Conceptual framework for defining disease modification in systemic lupus erythematosus: a call for formal criteria. Lupus Sci Med. 2022;9(1):e000634.
3. Van Vollenhoven RF, Mosca M, Bertsias G, Isenberg D, Kuhn A, Lerstrøm K, et al. Treat-to-target in systemic lupus erythematosus: Recommendations from an international task force. Annals of the Rheumatic Diseases. 2014;73(6):958-967.
4. Parra Sánchez AR, Voskuyl AE, van Vollenhoven RF. Treat-to-target in systemic lupus erythematosus: advancing towards its implementation. Nature Rev Rheumatol. 2022;18(3):146-157.
5. Mucke J, Kuss O, Brinks R, Schanze S, Schneider M. LUPUS-BEST—treat-to-target in systemic lupus erythematosus: study protocol for a three-armed cluster-randomised trial. Lupus Sci Med. 2021;8(1):e000516.
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7. Morand E, Pike M, Merrill JT, Vollenhoven RV, Werth VP, Hobar C, et al. Efficacy and safety of deucravacitinib, an oral, selective, allosteric TYK2 inhibitor in patients with active systemic lupus erythematosus: A phase 2, randomized, double-blind, placebo-controlled study. Ann Rheum Dis. 2022;81(Suppl 1):209.
8. Morand EF, Tanaka Y, Furie R, Vital E, van Vollenhoven R, Kalunian K, et al. Efficacy and safety of baricitinib in patients with systemic lupus erythematosus: Results from two randomised, double-blind, placebo-controlled, parallel-group, phase 3 studies. Ann Rheum Dis. 2022;81(Suppl 1):327-328.
9. BMS. Bristol Myers Squibb’s Applications for Deucravacitinib for the Treatment of Moderate to Severe Plaque Psoriasis Accepted by U.S. Food and Drug Administration and Validated by European Medicines Agency. https://news.bms.com/news/details/2021/Bristol-Myers-Squibbs-Applications-for-Deucravacitinib-for-the-Treatment-of-Moderate-to-Severe-Plaque-Psoriasis-Accepted-by-U.S.-Food-and-Drug-Administration-and-Validated-by-European-Medicines-Agency/default.aspx.
10. European Medicines Agency. Olumiant: EPAR: Product Information. https://www.ema.europa.eu/en/documents/product-information/olumiant-epar-product-information_en.pdf.
11. Schett G, Boeltz S, Müller F, Kleyer A, Völkl S, Aigner M, et al. CAR-T Cell treatment of refractory systemic lupus erythematosus - Safety and preliminary efficacy data from the first four patients. Ann Rheum Dis. 2022;81(Suppl 1):185-185.
12. Anders HJ, Federico R, Randhawa S, Leher H. Voclosporin is effective in achieving proteinuria treatment targets in lupus nephritis defined by EULAR/ERA recommendations. Ann Rheum Dis. 2022;81(Suppl 1):189-189.
13. Fanouriakis A, Kostopoulou M, Alunno A, Aringer M, Bajema I, Boletis JN, et al. 2019 Update of the EULAR recommendations for the management of systemic lupus erythematosus. Ann Rheum Dis. 2019;78:736-745.
14. Saxena A, Teng YKO, Collins C, England N, Leher H. Voclosporin for lupus nephritis: Results of the two-year AURORA 2 continuation study. Ann Rheum Dis. 2022;81(Suppl 1):325-325.