⚡CAR T for autoimmune disease

Good morning — it’s Saturday, November 15, and we’re covering new data on CAR T cell therapy in three autoimmune diseases, a first-of-its-kind study on UV fluorescent dermoscopy, and more.

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Bristol Myers Squibb reported encouraging Phase 1 results for its CD19 NEX-T™ CAR T cell therapy in three severe, refractory autoimmune diseases.

CD19 NEX-T is an autologous chimeric antigen receptor (CAR) T cell therapy that achieves deep B-cell depletion by targeting CD19 on B cells and plasmablasts. It uses the same CAR construct as Breyanzi (liso-cel), an approved oncology therapy, but is manufactured with a next-generation platform that shortens production to five days.

Data presented at ACR Convergence 2025 included 71 patients with systemic sclerosis (n = 26), idiopathic inflammatory myopathies (n = 13), and SLE (n = 32). Patients with inflammatory myopathies and SLE had failed a median of six and seven prior therapies, respectively.

The findings support the potential for immune reset. At the time of analysis, 94% of patients were off all chronic immunosuppressive therapy after a single infusion. Treatment induced robust CAR T cell expansion, complete B cell depletion, and re-emergence of a naïve B cell phenotype.

Patients with systemic sclerosis showed meaningful improvements in skin thickness. Median forced vital capacity also rose 10% in those with interstitial lung disease. According to the company, this response has not been seen with other therapies.

Among patients with inflammatory myopathies, characterized by severe muscle or skin involvement, 91% achieved a major or moderate response on the Total Improvement Score.

In the SLE cohort, all but one patient had symptom resolution by six months.

Safety was manageable. Cytokine-release syndrome was low grade in nearly all instances and resolved within days. Three patients experienced transient grade 3 neurotoxicity.

Questions remain about cost, access, and long-term durability and safety. Still, CAR T therapy may bring lasting, drug-free remission within reach.

Watch a 2-minute explainer on the CAR T process here.

> Ultraviolet dermoscopy enhances visualization of tumor borders, keratin structures, and melanoma-specific fluorescence: A multicenter study of 551 cutaneous tumors, published in JAAD, is the first large cohort to compare ultraviolet-induced fluorescent dermoscopy (UVFD) with polarized dermoscopy. The five most frequent diagnoses were basal cell carcinoma (28%), nevus (19%), melanoma (13%), seborrheic keratosis (12%), and squamous cell carcinoma (11%). Lesion borders were more clearly defined with UVFD (97% vs 76%; P < 0.001). UVFD improved visualization of three keratin-related structures: keratin (33% vs 24%), comedo-like openings (9% vs 5%), and fissures/ridges (4% vs 3%) (P < 0.001 for all comparisons). The non-keratin structure MAY globules, associated with basal cell carcinoma, was also more evident (2% vs 1%; P < 0.001). Notably, an “ochre” fluorescence appeared only in melanomas, present in 21% of cases (15/70). This feature was significantly more common in invasive melanomas (44%; 11/25) than with in situ disease (9%; 4/45) (P = 0.002). Limitations included the retrospective design, lack of non-polarized images, and multiple comparisons. Findings suggest UVFD may aid diagnosis and presurgical planning of cutaneous tumors. A set of exemplar UVFD images illustrating different diagnoses and their characteristic patterns is available for learning here.

> Denifanstat clears acne lesions in first trial of oral FASN inhibition: A Phase 2 dose-ranging trial published in JEADV found that oral denifanstat, a first-in-class fatty acid synthase (FASN) inhibitor, significantly reduced acne lesions without serious safety issues. Denifanstat inhibits fatty acid synthase, the terminal enzyme in the de novo lipogenesis pathway, reducing sebum production and inflammation. It is also in development for metabolic dysfunction–associated steatohepatitis (MASH). Investigators randomized 179 patients with moderate-to-severe acne to denifanstat (25–75 mg daily) or placebo. The 50 mg dose achieved the best efficacy–tolerability balance. At Week 12, this dose reduced inflammatory lesions by 65% vs 31% (P = 0.003), and non-inflammatory lesions by 58% vs 43% (P = 0.11). Safety was favorable; three severe events were considered unrelated to treatment. The most common adverse events (≥5%) were dry eye, dry skin, peeling, transient urine protein, and conjunctivitis. In September, Ascletis presented positive Phase 3 results in 480 patients with acne as a late breaker at EADV 2025. The company holds commercialization rights in China, while global developer Sagimet has initiated a Phase 1 trial of a second oral FASN inhibitor for acne in the U.S.

> Pilot study suggests MRF–isotretinoin combination may enhance acne and scar outcomes: A small trial published in JID suggests that microneedle radiofrequency (MRF) combined with low-dose isotretinoin yields superior acne clearance and scar improvement compared with isotretinoin alone. Eighteen adults with moderate-to-severe acne were randomized to low-dose isotretinoin for 8 weeks with or without three MRF sessions during the same period, followed by 12 weeks of observation. At Week 20, combination therapy produced higher non-inflammatory lesion clearance (94% vs 80%) and similar inflammatory lesion clearance (93% vs 90%), along with faster acne resolution. Scar improvement on the ECCA scale favored combination therapy (46% vs 5%; P < 0.001). Response rates were highest for rolling (100% vs 0%), followed by boxcar (50% vs 0%) and ice-pick (33% vs 0%) scars (P < 0.01 for all). Safety profiles were similar. A skin microbiota analysis was included to explore mechanisms. Mechanistically, MRF stimulates collagen and elastin synthesis to enhance scar remodeling. It may also improve acne by targeting sebaceous glands, reducing sebum production and alleviating inflammation. Limitations included the small sample size, unblinded design, and multiple comparisons. Although the findings suggest potential synergy, larger trials are warranted.

Quizzes, cases, and perspectives to sharpen your clinical eye.

The FDA has approved Galderma’s Restylane Lyft with lidocaine for chin augmentation in adults with mild-to-moderate chin retrusion. In a pivotal trial, 99% of investigators reported visible improvement at Month 3, and 95% maintained these results at Month 12. Patient satisfaction reached 86% at one year (More)

In a Phase 1 trial of 24 healthy volunteers, Oruka’s long-acting IL-23p19 antibody ORKA-001 was well tolerated and demonstrated an approximately 100-day half-life, suggesting the potential for once-yearly maintenance dosing in psoriasis (More)

A retrospective study of 329 patients with scabies found eggshell fragments in 77% of cases, representing the highest detection rate, followed by fecal pellets (39%), mites (36%), and eggs (28%). Eggshell fragments, the remnants of hatched scabies ova, may represent an underrecognized diagnostic marker (More)

A systematic review of 32 studies (n = 1,998) found modest efficacy for hydroxychloroquine in cutaneous dermatomyositis, with a 22% complete and 52% partial-or-complete response rate. Combination with glucocorticoids improved these outcomes to 46% and 72%. Cutaneous adverse events were common and often led to discontinuation. Limitations included the absence of randomized trials, reliance on small and retrospective studies, and variability in outcome definitions (More)

In a Canadian multicenter retrospective study of 179 adults and adolescents with atopic dermatitis, dupilumab maintained an 80% five-year drug survival rate, with 78% achieving clear or almost-clear skin (IGA 0/1) at Year 5. Discontinuations were mainly due to reduced effectiveness or adverse events, most commonly ocular surface disease (More)

The FDA has cleared the ellacor® System with Micro-Coring® technology for full-body skin resurfacing and Ultherapy PRIME for treating arm and abdominal skin laxity, expanding both devices beyond facial use (More: Ellacor) (More: Ultherapy)