⚡T-cell engager for immune reset

Good morning — it’s Saturday, November 1, and we’re covering a T-cell engager with the potential for immune reset in autoimmune disease, lebrikizumab’s every eight-week dosing in eczema, and more.

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A single course of teclistamab induced durable, drug-free remission in most patients with severe, refractory autoimmune diseases, according to a small study published in NEJM.

Teclistamab, already approved for multiple myeloma, is a bispecific T-cell engager antibody that targets CD3 on T cells and B-cell maturation antigen (BCMA) on B cells and plasma cells. BCMA is expressed on long-lived plasma cells that sustain autoantibody production. These cells persist despite standard B-cell–depleting therapies. By linking T cells to BCMA-positive plasma cells, teclistamab redirects T-cell cytotoxicity to eliminate them.

Investigators treated ten adults with six different refractory autoimmune diseases: systemic sclerosis, inflammatory myositis, rheumatoid arthritis, Sjögren’s syndrome, Graves disease, and IgG4-related disease. Half had cutaneous involvement. All had failed more than three immunomodulatory therapies.

Patients received step-up dosing of teclistamab over five days, followed by a single maintenance dose at Week 4. Before treatment, glucocorticoids were tapered to less than 5 mg per day, and all other immunosuppressive therapy was stopped.

Six patients remained in remission after up to 15 months of follow-up, and two achieved a second remission after retreatment. At the latest follow-up, six of seven had stopped glucocorticoids, and eight of ten had discontinued all immunosuppressive therapy.

Cytokine-release syndrome occurred in eight patients. All were mild to moderate and responded to tocilizumab. Infections were common but manageable. Every patient developed hypogammaglobulinemia, which was managed with immune globulin infusions. No neurotoxicity was seen.

By more deeply depleting BCMA-positive plasma cells, teclistamab may enable durable, treatment-free remission through a potential immune-reset mechanism. Larger controlled trials are warranted.

> Lebrikizumab maintains eczema control with only six injections a year: Lebrikizumab (Ebglyss) sustained long-term control in moderate-to-severe atopic dermatitis with dosing every eight weeks, maintaining efficacy nearly identical to treatment every four weeks. The findings come from the ADjoin addendum, a 32-week open-label extension of ADjoin. The study included 103 adults and adolescents who had completed 100 weeks of lebrikizumab on an every-4-week schedule. Investigators then re-randomized them to receive 250 mg every 8 weeks or every 4 weeks. EASI-75 responses (≥75% improvement in eczema severity) were maintained in both groups through Week 32: 84% → 86% in the 4-week arm and 82% → 79% in the 8-week arm. No new safety or immunogenicity signals emerged. Limitations included the open-label design, lack of power to test non-inferiority, and enrollment of only prior responders. Lilly has submitted these findings to the FDA to add an every-two-month maintenance dosing option. A study evaluating dosing every 12 weeks (four injections per year) is ongoing.

> Baricitinib drives triple-site regrowth in adolescents with severe alopecia areata: Lilly also announced positive one-year results from the Phase 3 BRAVE-AA-PEDS trial. The study, the largest of its kind, confirms the efficacy of baricitinib (Olumiant) in adolescents with severe alopecia areata. Participants had an average of 89% scalp hair loss at baseline. After 52 weeks of continuous therapy, 54% on 4 mg and 31% on 2 mg achieved ≥80% scalp coverage (SALT ≤ 20). A post-hoc analysis suggested earlier treatment, within 2 years of disease onset, yielded higher responses. At Week 52, 65% of patients on 4 mg had minimal or no eyebrow loss and 63% had minimal or no eyelash loss (ClinRO 0/1). No new safety signals emerged. The most common adverse events were acne, nasopharyngitis, and influenza. No deaths, venous thromboembolism, or major cardiovascular events occurred. Lilly plans to submit these adolescent data to global regulators for a potential Olumiant label update. The company has already begun enrolling the next cohort (ages 6–11) in BRAVE-AA-PEDS. Roughly 40% of alopecia areata cases begin in childhood, with early onset often linked to more extensive hair loss.

> Icotrokinra clears scalp, genital, nail, and hand/foot psoriasis in 52-week trial: Johnson & Johnson’s Phase 3 ICONIC-TOTAL trial found that icotrokinra, a first-in-class oral IL-23 receptor inhibitor, delivered durable clearance in psoriasis affecting high-impact sites. The study initially enrolled 311 patients with at least moderate psoriasis involving one or more high-impact sites: scalp, genital area, or hands/feet. Participants completed a 16-week placebo-controlled period followed by 36 weeks of open-label treatment. By Week 52, patients achieved high rates of clear or almost clear skin (IGA or PGA 0/1) across all major sites: scalp (72%), genital region (85%), and hands or feet (62%). Mean nail severity score improvement (mNAPSI) reached 62%. Adverse-event rates through one year mirrored those in the placebo-controlled period, with no new safety signals. High-impact site psoriasis significantly impairs daily function and quality of life. According to the International Psoriasis Council, patients with disease in these regions qualify for systemic therapy regardless of total body surface area affected.

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