Joseph F. Merola

Objectives: To evaluate the long-term efficacy of bimekizumab in patients with psoriatic arthritis (PsA) across the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) domains, PsA-related conditions, and comorbidities. Methods: Post hoc analysis of pooled data from BE OPTIMAL (NCT03895203; biologic-naïve patients) and BE COMPLETE (NCT03896581; patients with prior inadequate response/intolerance to tumour necrosis factor inhibitors) phase 3 studies, and their open-label extension BE VITAL (NCT04009499), which assessed subcutaneous bimekizumab 160 mg every 4 weeks in patients with active PsA. Efficacy was assessed to 3 years (Week 148) across GRAPPA core domains, PsA-related conditions (inflammatory bowel disease [IBD] and uveitis), and inflammatory markers of cardiovascular risk. Results: Among 1,112 bimekizumab-treated patients with PsA, improvements were sustained across the GRAPPA core domains to 3 years. Resolution of swollen and tender joint count at 3 years was achieved by 59.2% and 34.6% of patients, respectively, while 54.8% achieved ≥50% improvement from baseline in American College of Rheumatology response criteria (modified non-responder imputation [mNRI]). Enthesitis (LEI=0) and dactylitis (LDI=0) resolution was also achieved by 56.6% (mNRI) and 68.6% (NRI) of patients, respectively. A high proportion of patients achieved skin and nail psoriasis clearance (PASI100: 64.6%; mNAPSI=0: 68.0%; mNRI). IBD and uveitis events were rare, and inflammatory cardiovascular risk marker improvements were sustained. Conclusion: Bimekizumab provided long-term, sustained disease control across GRAPPA domains and systemic inflammation markers in patients with PsA, with low rates of IBD and uveitis, supporting its use as a long-term treatment for the heterogeneous manifestations of PsA. Clinical trial registration: BE OPTIMAL: NCT03895203; BE COMPLETE: NCT03896581; BE VITAL: NCT04009499

Biologic therapies have revolutionized treatment for patients with moderate to severe plaque psoriasis [1,2]. Over the past 2 decades, key proinflammatory cytokines have been identified as central ...

Objective: SLE is a chronic autoimmune disorder with a range of symptoms. While these are broadly reported in the literature, the symptom impact of SLE on patient health-related quality of life is less well documented. This qualitative interview study aimed to understand the nature and importance of skin symptoms, evaluate the content validity of the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) scale in SLE and assess what constitutes meaningful change in SLE-associated fatigue and skin symptoms. Methods: In August 2023, 60 min individual interviews were conducted virtually with 18 adults in the USA who self-reported a diagnosis of SLE and reported experiencing SLE-related fatigue within the prior 30 days. 17 participants also reported experiencing SLE-related skin symptoms. Participants described their experiences with these symptoms and their perceptions of the smallest meaningful improvement using their own words and using the Patient Global Impression of Severity (PGIS) and Patient Global Impression of Change (PGIC) scales. Cognitive debriefing was conducted to evaluate content validity of the 13-item FACIT-Fatigue scale (V.4) for SLE-related fatigue. Results: Of the 18 participants interviewed (mean age 51.7 years (range 33–67 years)), 17 were female and nine were white. All participants acknowledged that all items of the FACIT-Fatigue scale were relevant to SLE-related fatigue and most could comprehend and answer all items without difficulty. 13 participants indicated that a one-point improvement in fatigue on the PGIS would be meaningful. All participants with skin symptoms understood the skin-specific PGIS and PGIC items without difficulty. A one-point improvement on the PGIS and ‘a little better/moderately better’ on the PGIC represented meaningful improvements in skin symptoms by most participants. Conclusion: These results support the use of the FACIT-Fatigue scale in SLE trials and suggest that even minimal improvements in fatigue and skin symptoms are meaningful to patients.

The increasing use of targeted immunomodulatory therapies for psoriasis and atopic dermatitis has transformed disease management. However, paradoxical and treatment-induced cutaneous adverse and musculoskeletal events are being increasingly recognized that often mimic or deviate from the primary disease phenotype. This review summarizes current evidence on the clinical manifestations, underlying pathophysiological mechanisms, and therapeutic strategies for biologic-induced cutaneous and articular reactions in immune-mediated dermatoses. We highlight reactions associated with tumor necrosis factor, interleukin (IL)-17, IL-23, and IL-4/IL-13 inhibitors, discussing diagnostic challenges and immunologic shifts underlying these phenomena. Recognition of these distinct entities is critical to avoid misinterpretation as treatment failure and to optimize patient care through tailored management strategies and shared decision making.

Objective: To evaluate the efficacy and safety of guselkumab, an interleukin‐23p19 subunit inhibitor, in participants with active psoriatic arthritis (PsA) and inadequate response (inadequate efficacy and/or intolerance) to one prior tumor necrosis factor (TNF) inhibitor. Methods: In SOLSTICE (phase 3b, randomized, multicenter, double‐blind, placebo‐controlled study), enrolled adults with active PsA (three or more swollen joints; three or more tender joints; C‐reactive protein ≥ 0.3 mg/dL) and inadequate response to one prior TNF inhibitor were randomized to guselkumab 100 mg every 4 weeks (Q4W), guselkumab 100 mg at weeks 0 and 4 and then Q8W, or placebo with crossover to guselkumab Q4W at week 24. The primary endpoint was ≥20% improvement in American College of Rheumatology criteria (ACR20) at week 24. Secondary endpoints included ACR50, ACR70, Investigator's Global Assessment of psoriasis (IGA) score of 0 or 1 with ≥2‐grade improvement, ≥90% improvement in Psoriasis Area and Severity Index (PASI90), and minimal disease activity (MDA) at week 24 and were analyzed by intention‐to‐treat. Results: Analyses included 451 randomized participants (Q4W n = 150; Q8W n = 151; placebo n = 150). At week 24, significantly greater proportions of guselkumab (Q4W/Q8W)‐treated participants versus placebo‐treated participants, respectively, achieved ACR20 (primary endpoint: 58.6%/62.2% vs 34.8%), ACR50 (31.4%/32.1% vs 12.2%), ACR70 (17.5%/17.3% vs 2.0%), IGA 0/1 response (50.0%/57.3% vs 17.4%), PASI90 (49.4%/45.5% vs 12.0%), and MDA (18.8%/23.9% vs 5.4%) (all P < 0.001). Through week 24, 46.7%, 53.6%, and 48.3% of participants receiving guselkumab Q4W, guselkumab Q8W, and placebo, respectively, had one or more adverse event. One death occurred (myocardial infarction). Conclusion: Comparable efficacy was observed with both guselkumab regimens in participants with active PsA and inadequate response to one prior TNF inhibitor; safety findings were consistent with the known profile of guselkumab in patients with psoriatic disease. image

Objectives: Bimekizumab, a monoclonal IgG1 antibody that selectively inhibits IL-17F in addition to IL-17A, has demonstrated tolerability and clinical efficacy in patients with PsA. Here, we report an additional year of safety and efficacy of bimekizumab treatment to 3 years. Methods: BE OPTIMAL [NCT03895203; biologic DMARD (bDMARD)-naïve] and BE COMPLETE [NCT03896581; prior inadequate response/intolerance to TNF inhibitors (TNFi-IR)] assessed s.c. bimekizumab 160 mg every 4 weeks in patients with PsA. Study completers could enrol in the BE VITAL open-label extension (NCT04009499). Outcomes were reported as observed, or using modified non-responder or multiple imputation, to 3 years. Results: Overall, 546/299 (76.7/74.8%) bDMARD-naïve/TNFi-IR patients randomized to bimekizumab or placebo at baseline (Bimekizumab Total group) completed year 3. Treatment-emergent adverse event rates [exposure-adjusted incidence rate/100 patient-years (95% CI)] for bimekizumab-treated patients through 3 years were 164.2 (152.7–176.3) in bDMARD-naïve and 88.6 (79.1–98.9) in TNFi-IR patients, consistent with those at year 1 with no new safety signals identified. Response rates for efficacy outcomes were sustained up to 3 years; at year 1 and year 3, respectively, 56.1/50.4% and 53.2/55.2% of bDMARD-naïve/TNFi-IR patients achieved ACR50, 61.8/58.2% and 59.5/59.1% achieved swollen joint count resolution, and 64.7/66.2% and 61.9/67.5% had 100% improvement from baseline in Psoriasis Area and Severity Index. Responses for other efficacy measures were similarly sustained and consistent in bDMARD-naïve and TNFi-IR patients. Conclusion: Bimekizumab demonstrated sustained high levels of efficacy and tolerability to 3 years, supporting its suitability for long-term treatment in bDMARD-naïve and TNFi-IR patients with PsA. Trial registration: BE OPTIMAL: NCT03895203; BE COMPLETE: NCT03896581; BE VITAL: NCT04009499.

Background: Sézary syndrome (SS) and leukaemic mycosis fungoides (MF) are aggressive cutaneous T‐cell lymphomas (CTCLs) with poor prognosis and limited treatment options. Single‐cell RNA sequencing (scRNA‐seq) offers an opportunity to dissect malignant heterogeneity and immune dysregulation yet has been underutilized in leukaemic CTCL. Objectives: To define transcriptional heterogeneity within malignant T cells, identify immunomodulatory signals shaping the tumour microenvironment and uncover actionable vulnerabilities in SS and leukaemic MF. Methods: We analysed 144,321 peripheral blood mononuclear cells from 22 patients (SS or leukaemic MF) and 7 healthy controls using scRNA‐seq, with CITE‐seq and TCR‐seq in subsets. Public and prospectively collected datasets were integrated after rigorous per‐sample quality control, batch correction and malignancy assignment. Differential gene expression and cell–cell communication analyses were performed using complementary modelling approaches with correction for sparsity and multiple testing. Results: Three transcriptionally distinct malignant T‐cell (MTC) subtypes were identified: central memory‐like (MTC CM), effector/effector memory‐like (MTC E/EM) and regulatory‐like (MTC Reg), each with unique expression programmes and putative vulnerabilities. MTC CM, the dominant population, expressed central memory markers, Th2/Th22 skewing and a broader KIR repertoire ( KIR3DL2, KIR3DL1, KIR2DL3 ) than previously reported. MTC E/EM and MTC Reg were enriched for NR4A1 and ITGB1 , respectively. Cell–cell communication analysis revealed KIR–MHC‐I signalling and suggested that MTC‐derived TNF and IL‐10 may drive JAK/STAT pathway activity in non‐T cells, indicating an underrecognized dimension of tumour‐induced immune reprogramming. Conclusions: This is one of the most comprehensive single‐cell studies of leukaemic CTCL to date. We uncover new malignant T‐cell states, broaden the known repertoire of KIR expression, and propose mechanisms of immune evasion that may contribute to treatment resistance. These findings lay the groundwork for subtype‐specific and microenvironment‐informed therapeutic strategies in Sézary syndrome, with potential implications for guiding targeted therapy selection but require validation in larger, independent cohorts.

Background: Genital psoriasis is highly prevalent among patients with psoriasis, is often stigmatized, causes pain and discomfort and negatively impacts quality of life. Apremilast is an oral phosphodiesterase 4 inhibitor approved for treating psoriasis and has demonstrated safety and efficacy in treating genital psoriasis, as seen in the primary 16‐week DISCREET results. Objectives: To assess the efficacy and safety of apremilast 30 mg twice daily in patients with moderate to severe genital psoriasis over the 32‐week study duration. Methods: DISCREET was a phase 3, multicentre, randomized, double‐blind trial that evaluated apremilast 30 mg twice daily versus placebo in a 16‐week placebo‐controlled phase (randomization 1:1) followed by a 16‐week apremilast extension phase. Patients had moderate to severe genital psoriasis, defined as a modified static Physician's Global Assessment of Genitalia (genital PGA) score of ≥3. They also either had disease inadequately controlled by or were intolerant to topical therapy. We report the results through Week 32. Results: Of 289 patients randomized, 229 continued to the apremilast extension phase (Weeks 16–32): 110 in the placebo/apremilast group and 119 in the apremilast/apremilast group. At 32 weeks, 51.8% (95% CI: 42.6, 60.9) of patients in the placebo/apremilast group and 40.3% (95% CI: 32.0, 49.3) of patients in the apremilast/apremilast group had achieved a modified genital PGA response (score of 0/1 with ≥2‐point reduction from baseline). At Week 32, similar improvements in skin, genital signs and symptoms and quality of life were observed in patients who started apremilast at Week 16 or at randomization. Frequently reported treatment‐emergent adverse events during all‐apremilast exposure were diarrhoea (25.4%), nausea (19.4%) and headache (17.9%). Conclusions: Apremilast is an effective oral systemic therapy in patients with moderate to severe genital psoriasis and has shown consistent clinical efficacy, lessening of symptoms and quality‐of‐life benefit in DISCREET. Clinical trial ID : NCT03777436.