UCB Pharma (France)

BackgroundBlocking programmed cell death protein 1 (PD-1) has become a standard cancer immunotherapy, increasingly used in kidney, liver, or heart transplant recipients who develop skin cancer or hepatocellular carcinoma, despite the increased risk of graft failure or rejection. The mechanism of action of PD-1 blockade relies on stimulating CD8+ T cell activity, but its impact on humoral immunity in general and on alloimmunization in particular remains uncertain.ObjectiveThe aim of this study was to investigate the impact on anti-PD-1 treatment on alloimmunization.MethodsThe effect of anti-PD-1 treatment on the generation of anti-HLA (Human Leucocyte Antigen) antibodies was investigated in 72 patients with non-small cell lung cancer vaccinated with an allogeneic plasmacytoid dendritic cell line (PDC*line; six weekly injections), with or without pembrolizumab administered every three weeks. The kinetics and functionality of the anti-HLA generated were analyzed.ResultsThe results show that 51.4% of the patients developed anti-HLA antibodies, primarily dependent on the vaccine dose. In 60% of cases, the antibody response appeared after the sixth injection, peaked after one month, and then gradually declined over two years. Anti-HLA class II antibodies appeared earlier than class I antibodies. Functional assays demonstrated complement-dependent cytotoxicity against allogeneic B lymphocytes and PDC*line cells in the serum of some patients, with no difference related to treatment. PD-1 blockade did not alter the magnitude, kinetics, or cytotoxic potential of the vaccine-induced humoral response. ConclusionThese results indicate that, during allogeneic human vaccination, PD-1 signaling exerts a limited effect on antibody production and effector function, suggesting a more complex regulatory role in humoral immunity than previously thought.

IntroductionMyelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is a rare, autoimmune demyelinating central nervous system disease. Currently, little is known about the signs, symptoms, and health-related quality of life (HRQoL) impact of MOGAD from the patient perspective. This study explored the patient experience of MOGAD through concept elicitation interviews with patients with MOGAD and clinicians to develop a conceptual model of MOGAD.MethodsA preliminary conceptual model of MOGAD signs, symptoms, treatments, and HRQoL impacts was developed based on a review of the published literature. Thematic analysis of semi-structured interviews with patients and clinicians was used to develop the final conceptual model.ResultsTwelve patients with MOGAD and two clinicians were interviewed. The most common patient-reported symptoms were eye pain, fatigue, body aches/pain, headaches, and blurred vision. Eye pain and body aches/pain were reported as the most bothersome symptoms and most important to improve with treatment. The HRQoL impacts most commonly reported by patients were difficulty with carrying out household chores, inability to work, depression, and difficulty walking. Impacts on work/school were considered by patients as the most bothersome to their HRQoL and the most important to resolve. Following the interviews, a final conceptual model was produced that reported 32 symptoms across seven domains (constitutional; visual; general neurological; sensory-motor neurological; genitourinary; gastrointestinal; and chest-related, respiratory, and throat) and 50 HRQoL impacts across eight domains (emotional wellbeing, activities of daily living, physical functioning, social functioning, work/school, cognitive functioning, sleep, and financial).ConclusionsThis study provides important insights into the patient experience of MOGAD from patient and clinician perspectives, highlighting the underappreciated burden of the disease. The final conceptual model demonstrates the heterogeneity of MOGAD symptoms and their impact on patients’ HRQoL. Future treatment trials should consider including appropriate measures to evaluate the key symptoms and HRQoL impacts identified in this study.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40120-025-00770-6.

Hidradenitis suppurativa (HS) is a chronic, inflammatory skin condition which negatively impacts patients' physical and mental wellbeing. The HS Quality of Life questionnaire (HiSQOL©) was developed to assess HS-specific changes in health-related quality of life (HRQoL), one of the six domains of the core outcome set, established by the HS Core Outcomes Set International Collaboration. To evaluate the psychometric properties of HiSQOL total and domain scores and determine interpretation thresholds to guide score interpretation. Blinded, pooled data from two bimekizumab phase III trials (BE HEARD I & II) in adult patients with moderate-to-severe HS were used to conduct a confirmatory factor analysis (CFA) and to assess convergent validity [correlations with other patient-reported outcomes (PROs)], known-groups validity [grouping patients according to Hurley stage, International Hidradenitis Suppurativa Severity Score System (IHS4) and patient global impression of HS severity scale], reliability [Cronbach's α and intraclass correlation coefficients (ICCs)] and responsiveness (sensitivity to change). Clinically meaningful within-patient improvement thresholds were estimated by anchor- and distribution-based analyses. Symptom/impact severity thresholds were estimated by receiver operating characteristic curve analyses. The CFA models supported the relevance of the three subscales and an underlying unidimensional concept, validating the total score derivation from all items. HiSQOL subscale and total scores showed good convergent and known-groups validity, with HiSQOL scores being consistently higher (worse HRQoL outcomes) for patients with higher disease severity. HiSQOL demonstrated good internal consistency (Cronbach's α ≥ 0.81 for all scores) and test-retest reliability (ICC 0.73-0.83 across HiSQOL scores). Correlation coefficients between changes in HiSQOL scores and changes in other PRO scores were all positive and statistically significant (P-values < 0.001), with most exceeding 0.30, demonstrating acceptable responsiveness. Clinically meaningful within-patient improvement thresholds were estimated as: 20-21-point decrease for HiSQOL total score (total possible range 0-68), 5-6-point decrease for symptoms (range 0-16), 4-5-point decrease for psychosocial (range 0-20) and 10-11-point decrease for activities-adaptations (range 0-32). Thresholds for different levels of symptom/impact severity were derived. The HiSQOL subscale and total scores demonstrated robust psychometric properties, supporting the use of HiSQOL to interpret trial results and inform treatment decisions.

IntroductionHidradenitis suppurativa (HS) is a chronic inflammatory disease characterised by painful skin lesions which negatively impact patients’ physical and mental wellbeing. The HS Symptom Daily Diary (HSSDD) and HS Symptom Questionnaire (HSSQ) are patient-reported outcome (PRO) tools capturing patient-perceived severity of HS symptoms. Here, we report the psychometric properties of HSSDD and HSSQ along with score interpretation thresholds.MethodsPooled data from patients with moderate to severe HS in two phase 3 studies (BE HEARD I II) were analysed. Test-retest reliability was evaluated using intraclass correlation coefficients (ICCs). Convergent validity was assessed between the HSSDD (N = 934) and HSSQ (N = 1007) compared with relevant PROs and clinician-reported outcomes (ClinROs) at baseline and Week (Wk)16. Known-groups validity was assessed, comparing HSSDD and HSSQ scores between participant subgroups pre-defined using PRO/ClinRO measures (Patient Global Impression [PGI] of HS severity, Hurley stage, International HS Severity Score System). Responsiveness was evaluated by correlating changes from baseline to Wk16 in HSSDD and HSSQ scores with changes in PGI scales. Clinically meaningful within-patient improvement thresholds were estimated using anchor- and distribution-based analyses. Symptom/impact severity thresholds were estimated using receiver operating characteristic curve analyses.ResultsAt Wk16, HSSDD and HSSQ completion rates were 70.1% and 90.2%, respectively. Test-retest reliability analyses demonstrated good score reproducibility (ICC: HSSDD: 0.80–0.86; HSSQ: 0.73–0.82). Correlations between HSSDD and HSSQ scores and other PROs/ClinROs were generally consistent with predefined hypotheses, indicating good convergent validity. HSSDD and HSSQ scores discriminated between pre-defined subgroups, confirming known-groups validity. Sixteen-wk changes from baseline in HSSDD and HSSQ scores and anchors were moderately to strongly correlated (> 0.30), establishing responsiveness. Interpretation thresholds for both HSSDD and HSSQ were estimated.ConclusionHSSDD and HSSQ item scores demonstrated good psychometric performance in participants with moderate to severe HS. The clinically meaningful severity thresholds defined here could be used to assess treatment efficacy.Clinical Trial registrationNCT04242446; NCT04242498.Graphical Supplementary InformationThe online version contains supplementary material available at 10.1007/s13555-025-01346-w.

Overexpression of interleukin (IL)-17A and IL-17F significantly influences psoriasis pathology. Until recently, biologics targeting IL-17A alone, like secukinumab, were used to treat psoriasis. Bimekizumab is a monoclonal IgG1 antibody that targets both IL-17A and IL-17F. BE RADIANT was the first phase III trial to investigate switching from selective inhibition of IL-17A to dual inhibition of IL-17A and IL-17F. Bimekizumab has previously shown superior achievement of complete skin clearance [100% improvement from baseline in Psoriasis Area and Severity Index (PASI 100)] vs. secukinumab through 48 weeks. Switching from secukinumab to bimekizumab resulted in improved clinical responses. Over 2 years, no new safety signals were observed. To report the 3-year efficacy and safety of bimekizumab in patients with moderate-to-severe plaque psoriasis receiving continuous bimekizumab or switching from secukinumab after 1 year. The BE RADIANT phase IIIb randomized controlled trial had a 48-week double-blinded period, in which patients received bimekizumab [320 mg every 4 weeks (Q4W)] or secukinumab (300 mg weekly to week 4, then Q4W). At week 16, patients randomized to bimekizumab underwent re-randomization to receive Q4W or Q8W maintenance dosing. From week 48 onward (open-label extension), all received bimekizumab. In total, 336 patients randomized to bimekizumab and 318 randomized to secukinumab at baseline entered the open-label extension. More patients randomized to bimekizumab achieved PASI 100 (modified nonresponder imputation) at year 1 (74.9%) vs. those randomized to secukinumab (52.8%). PASI 100 response rates were maintained over 3 years in patients treated with bimekizumab (68.8%) and increased in those randomized to secukinumab switching to bimekizumab (68.8%). Bimekizumab was well tolerated to 3 years. In patients who received ≥ 1 bimekizumab dose, the most common treatment-emergent adverse events (TEAEs) over 3 years were nasopharyngitis, oral candidiasis and upper respiratory tract infection (exposure-adjusted incidence rates 12.2, 10.0 and 5.5/100 patient-years, respectively). Rates of TEAEs of interest, including serious infections, inflammatory bowel disease, and suicidal ideation and behaviour, did not increase with longer exposure to bimekizumab from 1 to 3 years. More than two-thirds of patients randomized to bimekizumab and those who switched from secukinumab to bimekizumab achieved and maintained complete skin clearance over 3 years of treatment. Over 3 years, bimekizumab was well tolerated and TEAE rates did not increase with longer exposure. NCT03536884.

Introduction: Hidradenitis suppurativa (HS) has substantial negative effects on patients’ lives,1 with debilitating symptoms, such as intense pain/fatigue/draining and odor, which lead to overall low quality of life (QoL).1,2 Bimekizumab (BKZ) is a humanized IgG1 monoclonal antibody that selectively inhibits interleukin (IL)-17F in addition to IL-17A; clinical efficacy was previously shown in the phase 3 BE HEARD I&amp;II trials.3 Here, the impact of BKZ on patient-reported outcomes (PROs) in patients with moderate to severe HS in BE HEARD I&amp;II is reported. Procedure/Study: Pooled data included an initial (Weeks [Wks]0–16) and maintenance (Wks16–48) treatment period. Patients were randomized 2:2:2:1 (initial/maintenance) to BKZ 320 mg every 2 wks (Q2W)/Q2W, BKZ Q2W/ Q4W, BKZ Q4W/Q4W or placebo (PBO)/BKZ Q2W. HS Symptom Questionnaire (HSSQ; each symptom item scored 0–10) mean values are reported to Wk48 for skin pain, itch, smell/odor, and drainage/oozing. Proportions of patients achieving minimal clinically important difference (MCID) for Dermatology Life Quality Index (DLQI; scored 0–30; improvement from baseline score ≥4) were reported at Wk16 and Wk48. Data are reported as observed case. Results: Overall, 1,014 patients were randomized to BKZ Q2W/Q2W (N=288), BKZ Q2W/Q4W (N=292), BKZ Q4W/Q4W (N=288), PBO/BKZ Q2W (N=146). Within each HSSQ item, similar baseline scores were observed across treatment groups. At Wk16, for skin pain, itch, smell/odor and draining/oozing, greater improvements (i.e. score reduction) from baseline were seen in BKZ- vs PBO-treated patients. HSSQ item scores were substantially reduced from Wk16 to Wk48 in Wk16 PBO/BKZ switchers, further decreases were observed in those continually treated with BKZ. At Wk16, a greater proportion of BKZ- vs PBO-treated patients achieved MCID in DLQI: BKZ Q2W/Q2W, 64.6%; BKZ Q2W/Q4W, 54.9%; BKZ Q4W/Q4W, 63.5% vs PBO, 49.1%. At Wk48, a greater proportion of patients continually treated with BKZ achieved MCID in DLQI vs at Wk16; Wk16 PBO/BKZ switchers attained similar proportions (BKZ Q2W/Q2W: 73.4%; BKZ Q2W/Q4W: 63.5%; BKZ Q4W/Q4W: 74.5%; PBO/BKZ Q2W: 76.5%). Conclusion: At Wk16, BKZ-treated patients achieved a reduction from baseline of HS symptoms: skin pain, itch, smell/odor, and drainage/oozing. Clinically meaningful health-related QoL improvements from baseline were observed and maintained/slightly improved through Wk48. PBO/BKZ switchers experienced improvements in PRO responses from Wk16 to Wk48 and achieved comparable outcomes at Wk48 to patients continually treated with BKZ.

A previous network meta-analysis established 16-week relative efficacy with bimekizumab, an inhibitor of interleukin (IL)-17F in addition to IL-17A, versus other treatments for patients with radiographic axial spondyloarthritis (r-axSpA; i.e., ankylosing spondylitis), including the IL-17A inhibitors secukinumab and ixekizumab. This matching-adjusted indirect comparison (MAIC) assessed 52-week relative efficacy of bimekizumab versus secukinumab and ixekizumab. Individual patient data from BE MOBILE 2 (bimekizumab 160mg; N = 220) were matched to pooled summary data from MEASURE 1/2/3/4 (secukinumab 150mg), MEASURE 3 (secukinumab 300mg; escalated dose for inadequate responders), COAST-V (ixekizumab) and COAST-V/-W (ixekizumab). BE MOBILE 2 patients were reweighted using propensity score weights based on age, sex, ethnicity, tumor necrosis factor inhibitor (TNFi) exposure, weight, baseline ASDAS and BASFI (secukinumab) and baseline BASDAI (ixekizumab), and 52-week efficacy outcomes from the trial recalculated. Odds ratios (OR) or mean difference for unanchored comparisons are reported with 95% confidence intervals (CI). At week 52, MAIC demonstrated that patients may have higher likelihood of improvement in key efficacy outcomes with bimekizumab versus secukinumab 150mg (e.g., ASAS40: [OR (95% CI): 1.48 (1.05, 2.10); p = 0.026]; effective sample size [ESS] = 177). Differences in 52-week efficacy outcomes between bimekizumab and secukinumab 300mg dose escalation were non-significant (ESS = 120). Bimekizumab versus ixekizumab 80mg comparisons (COAST-V only; ESS = 84) also suggested that differences were non-significant for most key efficacy outcomes. Other ixekizumab comparisons (COAST-V/-W; ESS = 45) suggested bimekizumab may have higher comparative efficacy for many of the same efficacy outcomes, however ixekizumab analyses were limited by poor population overlap, likely due to the greater proportion of patients with previous TNFi exposure. Patients treated with bimekizumab may have a higher likelihood of achieving improved longer-term efficacy versus secukinumab 150mg, suggesting bimekizumab may be a favorable therapeutic option for r-axSpA. Differences in efficacy outcomes with bimekizumab versus ixekizumab 80mg were mostly non-significant, depending on the populations considered.

Matching-adjusted indirect comparisons (MAIC) were used to assess the relative efficacy of bimekizumab 160mg every 4weeks (Q4W) compared to guselkumab 100mg Q4W or every 8weeks (Q8W) at 48/52weeks in patients with psoriatic arthritis (PsA) who were biologic disease-modifying antirheumatic drug-naïve (bDMARD-naïve) or with previous inadequate response or intolerance to tumor necrosis factor inhibitors (TNFi-IR). Relevant trials were identified as part of a systematic literature review. For patients who were bDMARD-naïve, individual patient data (IPD) from BEOPTIMAL (N = 431) was matched to summary data from DISCOVER-2 (Q4W, n = 245; Q8W, n = 248). For patients who were TNFi-IR, IPD from BE COMPLETE (n = 267) and summary data from COSMOS (Q8W, N = 189). Trial populations were re-weighted using propensity scores. Unanchored comparisons of recalculated bimekizumab and guselkumab 48- or 52-week non-responder imputation outcomes for 20/50/70% improvement in American College of Rheumatology score (ACR20/50/70) and minimal disease activity (MDA) index were analyzed. In patients who were bDMARD-naïve, bimekizumab was associated with a greater likelihood of ACR50 (odds ratio [95% confidence interval] 1.62 [1.07, 2.44]; p = 0.021), ACR70 (2.20 [1.43, 3.38]; p < 0.001), and MDA (1.82 [1.20, 2.76]; p = 0.005) compared to guselkumab Q4W at week52. Bimekizumab also had a greater likelihood of ACR70 response (2.08 [1.34, 3.22]; p = 0.001) and MDA (2.07 [1.35, 3.17]; p < 0.001) compared to guselkumab Q8W at week52. In patients who were TNFi-IR, bimekizumab had a greater likelihood in achieving all evaluated outcomes compared to guselkumab Q8W at week48/52 (ACR20, 1.77 [1.15, 2.72]; p = 0.010; ACR50, 1.56 [1.03, 2.36]; p = 0.037; ACR70, 1.66 [1.05, 2.61]; p = 0.028; and MDA, 1.95 [1.27, 3.02]; p = 0.003). According to MAICs, bimekizumab demonstrated greater or comparable efficacy on ACR50/70 and MDA outcomes than guselkumab in patients with PsA who were bDMARD-naïve and TNFi-IR at week48/52. Bimekizumab had a more favorable likelihood than guselkumab in achieving more stringent treatment outcomes. NCT03895203, NCT03896581, NCT04009499, NCT03158285, NCT03796858.