Новые методы лечения дают надежду на достижение ремиссии при системной красной волчанке

With novel therapies on the way, ‘the outlook is bright’ in lupus Key takeaways: - Novel therapies will be critical to achieving optimal outcomes in lupus. - More data are needed to validate early results for CAR T-cell therapy in lupus. Novel therapies may allow more patients with lupus to reach remission or low disease activity, according to a presenter at the AWIR annual conference. “Although there has been significant improvement in outcomes for patients with lupus over time, we are still witnessing excessive morbidity and mortality,” Richard A. Furie, MD, chief of the division of rheumatology at Northwell Health, told Healio. “Our goals are to reduce disease activity, prevent flares and damage, and ultimately put patients into remission. Although the achievement of these goals requires a multifaceted approach, the key to success will be novel therapies.” According to Furie, it will be essential to identify the primary unmet needs in lupus to optimize the chances of success. “The greatest unmet need remains in lupus nephritis,” he said. Severe extra-renal disease also continues to be a challenge for lupus management, but it is not the only concern, Furie added. “Even patients with just mild disease activity accrue damage,” he said. “We need to prevent damage. That means preventing flares. That means getting people off steroids.” If these goals are met, the likelihood of remission, along with quality of life, increases for patients. Novel therapies and approaches may help rheumatologists meet these goals, according to Furie. “Targeting the interferon pathway has become a very hot topic,” he said as he discussed the type I interferon-targeting agents anifrolumab (Saphnelo, AstraZeneca) and litifilimab (Biogen). In his presentation, Furie cited a 2025 study conducted by Manzi and colleagues that showed subcutaneous anifrolumab yielded a 56% BILAG-based Composite Lupus Assessment (BICLA) response rate, compared with 37% for placebo. Furie noted that anifrolumab maintained that response rate through the follow-up period, indicating an important step toward the goals of minimizing damage and inducing remission. Meanwhile, litifilimab, a monoclonal antibody to Blood Dendritic Cell Antigen 2 (BDCA2), has the capacity to “shut down” pro-inflammatory cytokines, he said. After successful phase 1 and 2 programs with litifilimab, the phase 3 TOPAZ trial is underway for patients with systemic lupus erythematosus, while the phase 3 AMETHYST trial assesses the drug for cutaneous lupus. “You should hear about results within the year,” Furie said. Targeting toll-like receptors 7/8 with agents such as enpatoran (Merck), afimetoran (Beeline Medicines) and E6742 (Eisai) may also be a promising approach in lupus, according to Furie. “Those receptors are upstream drivers of the interferon pathway, as well as neutrophil, myeloid and B-cell activation,” he said. Of those agents, enpatoran is furthest along in development. The phase 2 WILLOW trial program includes patients with cutaneous disease in cohort A and moderate-to-severe lupus in cohort B. “In cohort A, we saw an impressive signal,” Furie said. “In cohort B, not the case.” It is possible that patients with arthritis may have impacted the results in the second cohort, according to Furie. “Arthritis remains our nemesis in these SLE trials,” he said. B-cell targeting therapies also offer hope in the lupus treatment arena. “There are a lot of targets on B cells,” Furie said, noting that monoclonal antibodies, T-cell engagers and chimeric antigen receptor T-cell therapy all have shown encouraging data. In a post-hoc analysis of belimumab (Benlysta, GlaxoSmithKline), the drug demonstrated a significant impact on eGFR slope, which Furie said may be an important part of clinical trial programs. “Maybe eGFR slope should become an endpoint for studies because proteinuria is not a good endpoint,” he said. Additionally, the recently released ALLEGORY trial of the B-cell targeting therapy obinutuzumab (Gazyva, Genentech) yielded an SLE Responder Index (SRI) response rate of 77%, according to Furie. “I did not think we would get that high of a response in any lupus study with any drug,” he said. “All the key secondary endpoints were successful as well.” Regarding the promising early results surrounding CAR T-cell therapy in lupus, Furie said he believes more data are required before the strategy can truly live up to the enthusiasm. “We need to see more efficacy data and more safety data,” he said. However, despite these reservations, the broad range of therapies available and moving through trials in lupus is reason for optimism, according to Furie. “The outlook is bright for our patients with systemic lupus as new therapies will improve outcomes,” he said. For more information: Richard A. Furie, MD, can be reached at [email protected].