Evidence on developmental milestones in children with arthrogryposis multiplex congenita (AMC) under the age of five is scarce. This multisite cross-sectional study described developmental status and examined factors associated with milestone attainment in 143 children aged 0-66 months from a pediatric AMC Registry. Development was assessed using the Ages and Stages Questionnaire, Third Edition (ASQ-3), across Communication, Gross Motor, Fine Motor, Problem-Solving, and Personal-Social domains. Independent variables included demographic, perinatal, clinical, and parental factors. Gross Motor function was the most limited domain, with more than 90% scoring close to/below the ASQ-3 domain-specific cutoff (≥ 2 SD below normative mean). Personal-Social scores were unexpectedly low, and Fine Motor limitations were also frequent, with 53.1% scoring close to/below the cutoff. Communication and Problem-Solving were relative strengths. Longer neonatal intensive-care unit stays were linked to poorer Communication and Fine Motor scores, and higher birth weight was associated with better Problem-Solving performance. Specific joint contractures, particularly those affecting the neck, shoulder, elbow, and knee, were associated with lower performance across domains, while higher parental education was related to better Personal-Social outcomes. Developmental attainment in AMC is shaped by interactions among musculoskeletal, perinatal, and family factors, underscoring the importance of early, coordinated orthopedic, developmental and family-centered interventions.

OBJECTIVE:To evaluate guselkumab efficacy on dactylitis resolution (DR) and enthesitis resolution (ER), and their impact on subsequent disease control, in patients with active psoriatic arthritis (PsA) and prior inadequate response to tumour necrosis factor inhibitors (TNFi-IR). METHODS:In the Phase IIIb COSMOS trial, 285 adults with TNFi-IR PsA were randomized (2:1) to receive guselkumab 100 mg or placebo at Week (W)0, W4, then every 8 weeks until W44. The Dactylitis Severity Score (DSS) and Leeds Enthesitis Index (LEI) assessed dactylitis and enthesitis, respectively. This post hoc analysis evaluated associations between W24 DR or ER and W48 achievement of stringent disease control measures using logistic regression. RESULTS:At baseline, 103/285 (36.1%) patients had dactylitis (DSS ≥ 1) and 190/285 (66.7%) had enthesitis (LEI ≥ 1). Patients with dactylitis were more likely to have enthesitis, more joint (SJC/DAPSA) and skin involvement, higher PGA score and lower BMI vs those without dactylitis. Patients with enthesitis were more likely to be female, and have dactylitis, more joints affected (SJC/TJC/DAPSA) and worse physical functioning (HAQ-DI/SF-36 PCS) vs those without enthesitis. Greater proportions of guselkumab- vs placebo-treated patients achieved DR/ER (W24: 44.8%/39.7% vs 25.0%/18.8%); rates increased through W48 among guselkumab-randomized patients (67.2%/55.6%). W24 resolution was associated with W48 achievement of stringent measures, including ACR50/70, DAPSA LDA/remission, PASI100, PASDAS LDA/VLDA and MDA/VLDA (odds ratios: DR, 3.28-13.38; ER, 2.88-6.09). CONCLUSION:Guselkumab treatment resulted in high DR/ER rates through W48 in TNFi-IR PsA patients. W24 DR/ER was associated with W48 disease control, providing valuable insights for clinical decision-making based on W24 treatment responses.

Objectives Previous research has shown women with psoriatic arthritis (PsA) often have lower rates of clinical response but less severe radiographic damage. Few randomized controlled trials (RCTs) in PsA report sex-disaggregated results. We assessed sex-disaggregated radiographic progression (RP) in DISCOVER-2 ( NCT03158285 ) considering sex differences in structural damage and whether this is associated with early improvements in joint disease activity (DA). Methods Biologic-naïve pts with active PsA were randomized (1:1:1) to GUS 100 mg every 4 weeks (Q4W); GUS 100 mg at W0, W4, then Q8W; or placebo with crossover to GUS 100 mg Q4W at W24. Early (W8) response in joint DA, (based on clinical DA Index for PsA [cDAPSA LDA; ≤13]), was assessed among pts with cDAPSA >13 at BL, without adjustment for sex-specific differences at BL. Multivariate repeated measures mixed models assessed associations between sex and changes in total PsAmodified van der Heijde-Sharp [vdH-S] score through W100 (Figure 1). Results Of 739 PsA pts enrolled, 47.5% were female. At BL, female vs male pts were more likely to have dactylitis (60.6% vs 50.3%; p=0.0049), and on average had higher BMI (29.5 vs 28.4 kg/m 2 ; p=0.0144), lower CRP levels (1.6 vs 2.3; p<0.0001), less severe psoriasis (Psoriasis Area and Severity Index [PASI] score: 7.5 vs 12.1; p<0.0001), and more functional disability (Health Assessment Questionnaire–Disability Index [HAQ-DI] score: 1.4 vs 1.2; p<0.0001). BL cDAPSA (46.1 vs 46.4) and PsA-modified vdH-S (26.2 vs 25.5) scores were similar (p>0.05) between sexes. In unadjusted analyses of GUS-treated pts, male sex was associated with greater progression of structural damage through W100 (ΔLSM=1.02; p=0.0260). After adjusting for risk factors of RP, BL characteristics with sex-specific differences in the pooled cohort, disease duration and non-biologic DMARD use at BL, the difference between sexes in RP decreased but remained significant (ΔLSM=0.90; p=0.0406); LSM changes from BL in PsA-modified vdH-S scores in males vs females were 1.36 vs 0.69 (p=0.0502) at W52 and 2.22 vs 1.10 (p=0.0475) at W100 (Figure 1). Early (W8) cDAPSA LDA was achieved by 18.9% of men vs 15.3% of women. In men, this was associated with significantly less RP through W100; in females only, numerical differences were observed. Conclusion These results confirm the independent association of male sex with more rapid RP. The previously reported relationship between early improvement in joint DA and diminished RP,[1] was found to be stronger in males than females, which may be due to the lower rate of RP in females. References [1.] Mease PJ. Clin Rheumatol 2024;43(1):241-9.

OBJECTIVE:To describe functional mobility among children, adolescents, and young adults with arthrogryposis multiplex congenita (AMC) and identify factors associated with mobility outcomes. DESIGN:Multisite cross-sectional study. SETTING:Eight orthopedic hospitals for children. PARTICIPANTS:A total of 256 individuals (N=256) aged 5-21 years with a confirmed clinical diagnosis of AMC were recruited between October 2019 and December 2022. AMC subtypes included amyoplasia (n=122), distal arthrogryposis (n=62), and Central Nervous System (CNS)/syndromic AMC (n=39). INTERVENTIONS:Not applicable. MAIN OUTCOME MEASURES:Functional mobility was assessed using the mobility domain of the Functional Independence Measure for Children (WeeFIM) and the Gillette Functional Assessment Questionnaire (FAQ). Multivariable models were used to examine associations with perinatal and current clinical and environmental factors. RESULTS:Children with CNS/syndromic and amyoplasia subtypes demonstrated significantly lower WeeFIM scores (coefficients [Exp(B)]=0.74 and 0.85, respectively; both P<.05) and reduced odds of higher FAQ levels (adjusted odds ratio [AOR]=0.16 and 0.18, respectively; both P<.001) compared with those with distal arthrogryposis. Greater joint involvement, particularly at the knees, was a strong negative factor. Each additional perinatal joint contracture was associated with a 3.1% reduction in WeeFIM scores (Exp(B)=0.97, P<.001) and an 8.2% decrease in the odds of higher FAQ levels (AOR=0.92, P<.05). Current knee involvement was associated with a 27.7% reduction in WeeFIM scores (Exp(B)=0.72, P<.001) and nearly 90% lower odds of higher FAQ levels (AOR=0.10, P<.001). Parental unemployment (AOR=0.44, P<.05) and higher musculoskeletal surgical burden (AOR=0.24, P<.001) were significantly associated with poorer mobility. CONCLUSIONS:This is the largest cohort to date examining functional mobility in AMC. Clinical and socioeconomic factors identified may guide tailored rehabilitation strategies to promote positive outcomes in children with AMC.

OBJECTIVE:To evaluate the safety and tolerability of higher doses of sildenafil in neonates with hypoxic-ischemic encephalopathy (HIE) and brain injury. STUDY DESIGN:A phase 1b open-label dose-finding clinical trial in neonates with moderate-severe HIE and confirmed brain injury on a day-2 magnetic resonance imaging during therapeutic hypothermia (TH). Enteral sildenafil was administered every 12 hours (q12 h) for 7 days. All participants received an initial dose 2.0 mg/kg, and a second dose of 2.5 mg/kg. Starting from the third dose, group 1 received 2.5 mg/kg q12 h and group 2 received 3.0 mg/kg q12 h. Primary outcome was incidence of dose-limiting toxicities. Secondary outcomes explored day-30 neuroimaging and 18-month neurodevelopment. RESULTS:Among the 30 neonates born between October 2019 and December 2021, 20 displayed day-2 brain injury and 13 received sildenafil (8 in group 1; 5 in group 2). In group 1, 25% (2/8) experienced transient hypotension after the first dose, linked to antiseizure medications. No significant hypotension occurred in group 2 when sildenafil was administered separately. At the 3.0 mg/kg/dose, steady-state sildenafil concentrations persisted beyond TH. Death or significant 18-month neurodevelopmental impairment occurred in 50% (4/8) of group 1 and 60% (3/5) of group 2. Among the survivors, partial recovery of brain injury was seen in 80% (4/5) of group 1 and 75% (3/4) of group 2; cerebral palsy developed in 0% (0/5) and 50% (2/4), respectively. CONCLUSIONS:Enteral sildenafil up to 3.0 mg/kg q12 h was safe and well tolerated in a small single-center cohort of neonates with HIE treated with TH. Phase 2 trials are needed to assess multicenter feasibility and efficacy. TRIAL REGISTRATION:ClinicalTrials.gov NCT04169191.

OBJECTIVE:Evaluate guselkumab efficacy, an anti-interleukin-23p19-subunit antibody, in patients with active psoriatic arthritis (PsA) and inadequate response to 1 or 2 tumour necrosis factor inhibitors (TNFi-IR), utilizing composite indices assessing disease activity across disease domains. METHODS:In the Phase IIIb COSMOS trial, 285 adults with TNFi-IR PsA were randomized (2:1) to receive guselkumab 100 mg or placebo at Week (W)0, W4, then every 8 weeks through W44. Patients receiving placebo crossed over to guselkumab at W24. In this post hoc analysis, composite indices evaluated included the Disease Activity Index for Psoriatic Arthritis (DAPSA), Disease Activity Score 28 (DAS28), Psoriatic Arthritis Response Criteria (PsARC), Psoriatic Arthritis Disease Activity Score (PASDAS), GRAPPA Composite score (GRACE), modified Composite Psoriatic Disease Activity Index (mCPDAI), minimal disease activity (MDA), and very low disease activity (VLDA). Through W24, treatment failure rules were applied. Through W48, non-responder imputation was used for missing data. RESULTS:Greater proportions of guselkumab- than placebo-randomized patients achieved composite index endpoints relating to low disease activity (LDA; 14.8-52.4% vs 3.1-28.1%) or remission (3.7-5.3% vs 0.0-2.1%) at W24. Among guselkumab-randomized patients, LDA rates increased to W48 (DAPSA, 44.4%; DAS28, 47.8%; PASDAS, 34.4%; GRACE, 33.3%; mCPDAI, 40.2%), and 27.0% and 64.0% achieved MDA and a PsARC response, respectively. In the placebo→guselkumab crossover group, W48 response rates were similar to the guselkumab-randomized group. CONCLUSION:Guselkumab treatment provided substantial benefits across multiple disease domains, with increasing proportions of patients achieving LDA/remission over 1 year, highlighting the effectiveness of guselkumab despite previous inadequate response to TNFi.

Objectives Randomized controlled trials demonstrated the efficacy of IL-23 inhibitors (i) and IL-17i in PsA; however, real-world data on their effectiveness in heterogeneous patient subgroups are limited. Some subgroups, such as older, obese, or biologic-experienced patients, are of particular interest as they report worse outcomes.[1] The objective was to assess the 6-month persistence and effectiveness of guselkumab (GUS) and IL-17i across these subgroups of interest. Methods PsABIOnd ( NCT05049798 ) is a global observational study in patients with PsA starting GUS or IL17i as 1st-to-4th line of biologic therapy per their standard of care.[2] The full population of the PsABIOnd study over 6 months of follow up was analyzed. Analyses were performed according to initial treatment group allocation in the overall population and in specific subgroups defined by baseline (BL) age, sex, BMI categories, and prior biologic use. Persistence on treatment (ie, no stop/switch) over 6 months was assessed via the Kaplan-Meier estimator function. Propensity score (PS) analysis was used to evaluate hazard ratio (HR) of GUS vs IL-17i stop/switch prior to the 6-month visit, adjusting for BL variable imbalances across cohorts. Effectiveness was descriptively assessed using rates and means at BL and 6 months of the following measures: swollen and tender joint counts, clinical Disease Activity Index for PsA -based low disease activity /remission, the Leeds Enthesitis Index, psoriasis body surface area, Dermatology Life Quality Index and number of nails affected by psoriatic disease. Dactylitis was not assessed due to the low prevalence of dactylitis at BL. Results Of the 1134 pts analyzed, 555 and 579 pts received GUS or IL-17i, respectively, as their initial treatment. At BL, the GUS/IL-17i cohorts were generally well balanced across subgroups of interest: 83.4%/81.3% were <65 years of age; 60.4%/59.2% were female; 48.0%/43.4% had BMI≥30 kg/m2; and 63.4%/62.3% had previously received ≥1 targeted therapy. Persistence on treatment was high in both cohorts, with 526/555 (94.8%) GUS and 539/579 (93.1%) IL-17i pts remaining on their initial treatment at the 6-month visit (PS-adjusted HR of GUS vs IL-17i stop/switch [95% confidence interval]: 0.93 [0.75-1.16]); (Figure 1). Across patient subgroups of interest, similar improvements in joint symptoms enthesitis skin involvement, and psoriatic nail disease were observed with GUS and IL-17i at the 6-month visit. Conclusion Treatment with GUS or IL-17i resulted in comparable treatment persistence and effectiveness, regardless of age, sex, BMI, or treatment history, through 6 months. These results support the real-world effectiveness of GUS and IL-17i across PsA subpopulations. References [1.] Haddad A. Semin Arthritis Rheum 2025;152737. [2.] Siebert S. Rheumatol Ther 2023;10:489.

Targeted drugs in PsA have demonstrated efficacy in randomized controlled trials, including aspects of patient-reported impact. However, comparison data from observational studies are scarce, particularly for IL-23 and IL-17 inhibitors (i). As part of the 6 month (M) interim analysis of the first ≥600 participants (pts) enrolled in the PsABIOnd observational study, we assessed changes from baseline (BL) in PsA Impact of Disease-12 (PsAID12) following biologic treatment initiation. PsABIOnd ( NCT05049798 ) is an ongoing international, prospective study in 1300 planned PsA pts starting guselkumab (GUS) or IL-17i as first- to fourth-line biologic therapy (monotherapy or in combination with other agents) per standard clinical practice.[1] All enrolled pts with available PsAID-12 data at BL and the 6M visit (± 3M) were analyzed according to their treatment group (regardless of later switches). Impact of PsA was assessed with PsAID-12 comprising 12 items (including pain, fatigue, skin problems, etc.) scored 010, with higher values indicating a worse state. Mean change from BL in PsAID-12 subdomain and total scores, and proportions of pts achieving minimal clinically important improvement (MCII, ≥1.4) at the 6M visit were determined. Propensity score (PS) analysis evaluated treatment effect for the change in PsAID-12 total score and MCII (using nonresponder imputation), adjusting for BL imbalances across cohorts. Subdomain analyses were descriptive. At the Jan 2024 cutoff date, 323 and 296 pts receiving GUS or IL-17i, respectively, with PsAID-12 data available at BL and the 6M visit were analyzed. In both cohorts, PsAID-12 subdomains with highest impact at BL were pain, fatigue, and discomfort. At the 6M visit, mean (95% confidence interval [CI]) changes from BL in PsAID-12 total score were similar in the GUS (−1.5 [−1.7; −1.3]) and IL-17i (1.6 [1.8; 1.3]) cohorts. PS-adjusted treatment effect (regression coefficient [95% CI]) for GUS vs IL17i in change from BL in PsAID-12 total score was not significant (0.2 [−0.3; 0.6]). Proportions of pts achieving MCII in PsAID-12 total score at the 6M visit were 53% and 48% in the GUS and IL-17i cohorts, respectively, with a non-significant PS-adjusted treatment effect (odds ratio [95% CI]: 1.2 [0.8; 1.8]). Mean changes from BL in subdomain scores were similar across cohorts (Figure 1). Figure 1: Mean change from baseline in PsAID-12 subdomain scores with guselkumab and IL-17i at the 6M visit Last observation carried forward was imputed for participants with no 6M visit. Propensity score-adjusted treatment effect (regression coefficient [95% CI]) for GUS vs IL-17i for pain; fatigue; skin problems; work/leisure activities; functional capacity; discomfort; sleep disturbance; coping; anxiety, fear and uncertainty; embarrassment/shame; social participation; and depression were: 0.4 (−0.2,0.9); 0.1 (−0.5, 0.6); −0.1 (−0.8, 0.6); 0.1 (−0.6, 0.7); 0.1 (−0.5, 0.7); 0.3 (−0.3,1.0); 0.2 (−0.4, 0.9); 0.4 (−0.3,1.0); 0.1 (−0.5, 0.7); −0.01 (−0.7, 0.6); 0.1 (−0.6, 0.8); and −0.1 (−0.6, 0.5), respectively. For participants who switched/stopped initial treatment, data occurring after the switch or stop was excluded from the analysis. By 6M of treatment, clinically meaningful improvements in PsAID-12 total score were seen in around half of pts treated with GUS or IL-17i, with similar magnitudes of effect across subdomains in both cohorts. These results may be useful in shared treatment decision-making. [1.] Siebert S. Rheumatol Ther 2023;10:489.

Many drugs are available in PsA and have demonstrated efficacy in randomized controlled trials (RCTs); however, real-world long-term data of drugs are scarce. PsABIOnd is a large, ongoing, global observational study in PsA. The aim of this interim analysis of the first ≥600 participants (pts) enrolled out of 1300 planned pts in PsABIOnd was to assess treatment persistence and achievement of clinical PsA outcomes at 6 months (M). PsABIOnd ( NCT05049798 ) is an ongoing observational study in PsA pts starting guselkumab (GUS) or IL17 inhibitors (i) as 1st-to-4th line of biologic therapy (monotherapy or in combination with other agents) per standard of care. The primary outcome is treatment persistence at 36M.[1] In this interim analysis, the subset of pts enrolled in the PsABIOnd study who had an assessment at the 6M visit (± 3M) were analyzed according to their initial treatment, regardless of later switches. Persistence on treatment (ie, no stop or switch) was assessed over 6M via the Kaplan-Meier estimator function. Propensity score (PS) analysis was used to evaluate hazard ratio of stopping or switching GUS vs IL-17i prior to the 6M visit, adjusting for baseline (BL) imbalances across cohorts. Effectiveness was assessed at the 6M visit (descriptive unadjusted reports) by treatment line and included rates of achievement of low disease activity (LDA)/remission (REM) by clinical Disease Activity Index for PsA (cDAPSA) and DAPSA, minimal disease activity (MDA), psoriasis body surface area (BSA)<3%, resolution of enthesitis by Leeds Enthesitis Index and dactylitis. As of 08-Jan-2024 (cutoff date), 360 and 326 pts receiving GUS or IL-17i, respectively, as their initial treatment had follow-up data at the 6M visit: mean (GUS/IL-17i) age at BL was 52.0/53.6 years, and 63.1%/63.8% pts had previously received ≥1 targeted drug. Treatment persistence at the 6M visit was high, with 339/360 (94.2%) GUS pts and 304/326 (93.3%) IL-17i pts remaining on their initial treatment line (PS-adjusted hazard ratio of GUS vs IL-17i stop/switch [95% confidence interval (CI)]: 0.87 [0.47-1.61]). Reasons for initial treatment line discontinuation were comparable between groups. Treatment effectiveness was similar for GUS vs IL-17i at the 6M visit (Figure 2), with similar rates of pts achieving cDAPSA LDA/REM, DAPSA-LDA/REM, BSA<3%, MDA, LEI resolution, and dactylitis resolution. Figure 2. Achievement of PsA clinical outcomes with guselkumab and IL-17 inhibitors at the 6M visit (+/−3M) Rates of achievement (95% CI) of PsA clinical outcomes at the 6M visit (+/− 3M) are shown by initial treatment line and included rates of achievement of LDA/REM by cDAPSA and DAPSA (among pts with polyarticular PsA at BL), MDA (among non-MDA achievers at BL), psoriasis BSA<3% (among pts with BSA≥3% at BL), and resolution of enthesitis by LEI (among pts with LEI≥1 at BL) and dactylitis (among pts with dactylitis at BL). Number of participants (N) indicated under the x-axis correspond to the number of participants included in each respective analysis (see Methods). Last observation carried forward was imputed for participants with no 6M visit. PsA pts had similar persistence on treatment with GUS or IL17i, and comparable rates of effectiveness across various PsA domains at 6M. These results provide additional information on real-world effectiveness and support efficacy data from RCTs. [1.] Siebert S. Rheumatol Ther 2023;10:489-505.

AIM:To establish the construct validity, agreement, and minimal important difference (MID) of widely used mobility measures in arthrogryposis multiplex congenita (AMC). METHOD:Participants (n = 248, 126 males, mean age 10 years 10 months, standard deviation 3 years 11 months) with AMC were assessed using the Functional Mobility Scale (FMS), Gillette Functional Assessment Questionnaire (FAQ), Functional Independence Measure for Children (WeeFIM), and Patient-Reported Outcomes Measurement Information System (PROMIS). Convergent and discriminant validity were evaluated using Spearman's rank correlations, while known-groups validity was examined using analysis of variance. Cohen's kappa and distribution-based methods were used to estimate agreement and MIDs respectively. RESULTS:Robust convergent (ρ = 0.66-0.82, 95% confidence interval [CI] 0.54-0.86) and discriminant (ρ = 0.06-0.31, 95% CI -0.11 to 0.43) validity were found for all four mobility measures. Known-groups validity was supported by significant mean differences across AMC subtypes (amyoplasia, distal arthrogryposis, central nervous system/syndromic; p < 0.001). The measures also showed weak to good agreement in classifying mobility. A difference of one and two levels on the FMS and FAQ respectively, was found to be minimally important. For the PROMIS and WeeFIM, estimated MID values were 3.19 to 4.34 and 14.24 respectively. INTERPRETATION:The robust construct validity, agreement, and MIDs provide clinicians and researchers with evidence-based benchmarks for assessing mobility in children with AMC.

Background: Psoriatic arthritis (PsA) is a chronic, autoimmune, heterogeneous disorder with six key domains, including peripheral arthritis, axial disease, enthesitis, dactylitis, and psoriatic skin and nail disease. Previous analyses of DISCOVER-1 and -2 (D1 and D2) have shown the fully human IL-23p19-subunit inhibitor guselkumab (GUS) to be associated with robust and sustained improvement in PsA signs/symptoms over 52 weeks (W) in subgroups of patients (pts) across a variety of baseline (BL) demographic and disease characteristics.1 The efficacy of GUS explicitly in PsA pts with severe disease activity (DA) has not been assessed. Objectives: Evaluate the efficacy of GUS through W100 in bionaive PsA pts with severe DA based on a range of composite and pt-reported outcomes. Methods: D2 enrolled bionaive adults with active PsA (≥5 swollen [SJC] and ≥5 tender [TJC] joints, CRP ≥0.6 mg/dL). Pts were randomized (1:1:1) to GUS 100 mg every 4 weeks (Q4W); GUS 100 mg at W0, W4, Q8W; or placebo (PBO) with crossover to GUS Q4W at W24. In this analysis, severe DA was defined based on clinical DA Index for PsA (cDAPSA >28), PsA DA Score (PASDAS >5.4), and pt global assessment (PtGA ≥80mm) criteria. cDAPSA is calculated by summing individual scores for SJC, TJC, PtGA, and pt assessment of pain; PASDAS takes into account SJC, TJC, dactylitis and enthesitis scores, CRP, physician global assessment of disease activity, PtGA, and the physical component of the 36-Item Short Form Health Survey. Least square mean (LSM) changes from BL in the respective outcomes used to define each cohort were estimated with mixed models for repeated measures, adjusted for treatment group, BL outcome levels, and the study stratification factors (BL csDMARD use and high-sensitivity serum CRP value). Results: Among the 739 pts enrolled in D2, 648 (88%), 639 (86%), and 218 (29%) met the cDAPSA (mean=49.5), PASDAS (mean=6.8), and PtGA (mean=89.0) criteria for Severe DA. Overall, the BL characteristics were generally consistent across cohorts, although the Severe PtGA cohort was characterized by higher average CRP levels; mean scores reflecting worse joint and skin disease activity, pain, fatigue, and physical function; and less common csDMARD use (Table). Treatment groups were generally well balanced across Severe DA cohorts, except pts in the GUS Q4W group were more likely to be male and have dactylitis compared with PBO pts (data not shown).In multivariate analyses, irrespective of Severe DA cohort, GUS-treated pts experienced significantly greater improvements compared with PBO in all studied outcomes, with the largest effect seen in the Severe PtGA cohort (Figure 1). On average, improvements with GUS were clinically meaningful as of the first assessment timepoint, specifically W2 for cDAPSA (GUS Q4W: -5.9; GUS Q8W: -7.2; PBO: -5.0) and W8 for PASDAS (GUS Q4W: -1.5; GUS G8W: -1.5; PBO: -0.9) and PtGA (GUS Q4W: -30.0; GUS G8W: -32.1; PBO: -17.4) (Figure 1). Differences vs. PBO were enhanced through W24 across Severe DA cohorts, at which time further improvements with GUS Q4W/Q8W were observed, resulting in differences vs PBO of -9.8/-9.0, -1.1/-1.1, -24.0/-20.2, respectively, in cDAPSA, PASDAS, and PtGA, respectively. Further improvements in all studied outcomes (ΔcDAPSA from BL ̴ -36; ΔPASDAS from BL ̴ -3.6; ΔPtGA from BL ̴ -56) were observed through 2 years of GUS treatment, representing ̴73% improvement in joint disease activity, ̴53% improvement in PsA activity across domains, and ̴63% improvement in pt-reported overall disease activity. Conclusion: In bionaive PsA pts with severe DA based on a range of joint-focused and multi-domain outcomes, GUS led to rapid (W2 for joint and W8 for overall disease activity) clinically meaningful improvements in disease activity; these improvements were further enhanced by W24 and sustained through 2 years. Overall, findings support the use of GUS for the treatment of PsA pts presenting with severe DA. REFERENCES: [1] Ritchlin CT. RMD Open. 2022;8:e002195 Acknowledgements: NIL. Disclosure of Interests: Christopher T. Ritchlin - Consultant: AbbVie, Amgen, Eli Lilly, Gilead, Janssen, Novartis, Pfizer, and UCB, Grant/research support: AbbVie, Amgen, and UCB, Ennio Lubrano - Consultant: AbbVie, Amgen, Eli Lilly, GSK, Janssen, Novartis, and UCB, Maria Sole Chimenti - Speakers bureau: Eli Lilly, AbbVie, UCB, Novartis, and Janssen, Grant/research support: Eli Lilly, AbbVie, UCB, Novartis, and Janssen, Evan Leibowitz - Shareholder: Johnson & Johnson, Employee: Janssen Scientific Affairs, LLC, Mohamed Sharaf - Shareholder: Johnson & Johnson, Employee: Janssen EMEA, Dubai United Arab Emirates, Emmanouil Rampakakis - Employee: JSS Medical Research, Consultant: Janssen, Francois Nantel - Shareholder: Johnson & Johnson, Consultant: Janssen, Frédéric Lavie - Shareholder: Johnson & Johnson, Employee: Immunology Global Medical Affairs, Janssen Pharmaceutical Companies, Atul Deodhar - Speaker’s bureau: AbbVie, Eli Lilly, Janssen, Novartis, Pfizer, and UCB, Consultant: AbbVie, Amgen, Aurinia, BMS, Celgene, Eli Lilly, GSK, Janssen, MoonLake, Novartis, Pfizer, and UCB, Grant/research support: AbbVie, Eli Lilly, GSK, Novartis, Pfizer, and UCB.

Introduction Les études observationnelles fournissent des informations importantes sur l’efficacité des traitements, or il y a peu de données sur l’utilisation des inhibiteurs de l’IL-17 (IL-17i) et de l’inhibiteur de l’interleukine-23 (IL-23p19i) guselkumab (GUS) en vie réelle pour le traitement du rhumatisme psoriasique (RhPso).Objectif : obtenir un aperçu du profil des patients atteints de RhPso initiant un traitement avec GUS ou un IL-17i en vie réelle via une analyse intérimaire des patients inclus dans l’étude observationnelle PsABIOnd. Patients et méthodes PsABIOnd est une étude de cohorte prospective, observationnelle menée dans 20 pays évaluant la persistance, l’efficacité et la sécurité du traitement chez les adultes atteints de RhPso initiant GUS ou un IL-17i en 1re, 2e, 3e ou 4e ligne de biothérapie. D’août 2021 à mai 2023, sur les 1300 patients prévus, 586 ont été inclus, dont 483 ayant des données à l’inclusion disponibles et analysables. Cette analyse intermédiaire décrit les caractéristiques sociodémographiques, les traitements antérieurs et concomitants du RhPso, les comorbidités et les paramètres de la maladie à l’inclusion, y compris les résultats rapportés par les patients (PRO). Résultats Au total, 263 patients ont initié un traitement par GUS et 220 par un IL-17i. Les cohortes GUS/IL-17i étaient comparables en termes de caractéristiques sociodémographiques, maladie des patients et traitements concomitants du RhPso (Tableau 1, Tableau 2). GUS et IL-17i étaient principalement prescrits en 1re (33 %/36 %, respectivement) ou 2e (27 %/34 %) ligne de biothérapie. Parmi les patients bioexpérimentés, davantage de patients ont initié GUS vs un IL-17i en raison d’un échec primaire (30 %/22 %). Les comorbidités les plus courantes dans les cohortes GUS/IL-17i étaient les maladies cardiométaboliques (48 %/44 %) et l’obésité (44 %/34 %). Les scores moyens de cDAPSA/DAPSA (26,4–28,8) indiquaient une activité modérée à sévère de la maladie au niveau articulaire. Le nombre d’articulations douloureuses (4,3/4,6) et gonflées (10,1/11,4) ; la proportion de patients présentant une enthésite (52 %/56 %), une dactylite (18 %/20 %), une atteinte unguéale (44 %/47 %) et une atteinte axiale (33 %/34 %) ; et les PROs, étaient similaires entre les cohortes, suggérant une maladie à plusieurs domaines avec un impact important sur la fonction physique et la productivité au travail. Une proportion plus élevée de patients recevant GUS présentait un psoriasis sévère (14 %/7 % avec une SCA>10 %) et un indice moyen de qualité de vie (DLQI) plus sévère (7,9/5,5) (Tableau 2). Conclusion Dans cette analyse intérimaire de l’étude PsABIOnd, des patients atteints de RhPso ont été traités avec GUS ou un IL-17i en 1re ou de 2e ligne dans 60 à 70 % des cas. Les patients traités présentaient une activité de la maladie modérée à sévère au niveau articulaire, une maladie multi-domaine et une altération de l’activité et de la productivité au travail. Comparé aux patients traités par IL-17i, GUS était plus souvent prescrit chez les patients atteints d’une maladie cutanée plus sévère. Ces résultats donnent un aperçu des schémas de prescription et peuvent être utiles pour interpréter les données à venir sur l’efficacité en vie réelle.

Introduction Les biothérapies ont démontré leur efficacité dans le rhumatisme psoriasique (RhPso) dans le cadre d’essais cliniques, cependant, les données de comparaison issues d’études observationnelles sont rares, en particulier pour les inhibiteurs de l’IL-23 et de l’IL-17. Dans le cadre de l’analyse intermédiaire à 6 mois des premiers≥600 participants inclus dans l’étude PsABIOnd sur le RhPso, les changements du Psoriatic Arthritis Impact of Disease (PsAID-12) par rapport à l’inclusion ont été évalués. Patients et méthodes PsABIOnd est une étude de cohorte observationnelle prospective internationale, comprenant 1300 participants atteints de RhPso et évaluant l’efficacité du traitement par guselkumab (GUS) ou un inhibiteur de l’IL-17 (IL-17i) de la 1ere à la 4ème ligne de biothérapie. Tous les patients avec des données disponibles sur le PsAID-12 à l’inclusion et lors de la visite à 6 mois ont été analysés. Le PsAID-12 est utilisé pour évaluer l’impact du RhPso, il comprend 12 éléments, notés de 0 à 10, les valeurs plus élevées indiquant un plus grand impact. Les résultats comprennent les changements moyens dans les sous-domaines et les scores totaux du PsAID-12, ainsi que les proportions de patients atteignant une amélioration minimale cliniquement importante (MCII, changement≥1,4) lors de la visite à 6 mois. Une analyse par score de propension (SP) a évalué l’effet du traitement sur le changement du PsAID-12 et de MCII en ajustant sur les déséquilibres des variables à l’inclusion entre les cohortes. Les analyses des sous-domaines étaient descriptives. Résultats En janvier 2024, 323 patients recevant du GUS et 296 recevant un IL-17i et disposant de données sur le PsAID-12 à l‘inclusion et lors de la visite à 6 mois, ont été analysés. Dans les deux cohortes, les sous-domaines du PsAID-12 ayant le plus grand impact à l’inclusion étaient la douleur, la fatigue et l’inconfort. Lors de la visite à 6 mois, les changements moyens du PsAID-12 (intervalle de confiance [IC] à 95 %) par rapport à l’inclusion étaient similaires dans les cohortes GUS (−1,5 [−1,7 ; −1,3]) et IL-17i (1,6 [1,8 ; 1,3]) (Fig. 1A). L’effet du traitement ajusté sur le SP (coefficient de régression [IC à 95 %]) pour GUS vs IL-17i dans le changement du PsAID-12 n’était pas significatif (0,2 [–0,3 ; 0,6]). Les proportions de patients atteignant une MCII dans le PsAID-12 lors de la visite à 6 mois étaient de 53 % avec GUS et 48 % avec IL-17i (Fig. 1B), avec un effet du traitement ajusté sur le SP non significatif (rapport des cotes [IC à 95 %] : 1,2 [0,8 ; 1,8]). Lors de la visite à 6 mois, les changements moyens par rapport à l’inclusion dans les scores des sous-domaines étaient similaires entre les cohortes, allant de 0,8 (−1,1 ; −0,5) pour la dépression à −2,3 (−2,7 ; −2,0) pour les problèmes de peau avec GUS, et de 0,8 (1,1 ; −0,5) pour la dépression à 1,9 (−2,2 ; −1,5) pour l’inconfort avec l’IL-17i (Fig. 2). Conclusion Au bout de 6 mois de traitement, des améliorations cliniquement significatives du PsAID-12 ont été observées chez environ la moitié des patients traités avec GUS ou IL-17i, avec des magnitudes d’effet similaires dans les sous-domaines des cohortes. Ces résultats peuvent être utiles dans la prise de décision partagée pour le traitement.

Background: Rheumatoid arthritis (RA) has a major impact on patients (pts), particularly around quality of life and activity impairment. While the association between clinical manifestations and patient-reported outcomes (PROs) has been demonstrated, the independent effect of specific joint involvement on PROs and their change over time has not been fully elucidated. Objectives: To describe the independent effect of overall and specific joint involvement and their changes over time on PROs in pts with RA treated with abatacept. Methods: This post hoc analysis involved 290 adult RA pts initiated on treatment with abatacept in the Abatacept Best Care (ABC) study (NCT03274141)1. The analysis investigated the association of Tender Joint Count (TJC-28), Swollen Joint Count (SJC-28) and involvement (tender and/or swollen) of five joint groups (shoulder, knee, elbow, wrist, and hand) with changes from baseline (BL) to 12 months (12M) of follow-up in selected PROs: Pt Global Assessment (PtGA), Pt Pain, Pt Fatigue, Health Assessment Questionnaire-Disability Index (HAQ-DI), Routine Assessment of Patient Index Data 3 (RAPID3), Work Productivity and Activity Impairment - Activity Impairment (WPAI-AI) score. Simple linear regression was used to test the association between BL and changes from BL to 12M in TJC and SJC with changes in each PRO at 12M. Multivariate linear regression adjusting for the five available joint groups examined the independent effect of BL and changes from BL to 12M in these joint groups on changes in each PRO at 12M. Results: Among 290 pts, the mean (SD) age was 60.1 (11.6) years, 73.8% were female, and the mean (SD) RA duration was 7.7 (9.0) years. Table 1 describes joint involvement (tender and/or swollen) at BL and the change from BL to 12M for 289 pts with 12M data. Mean (SD) TJC and SJC at BL were 9.6 (6.2) and 7.9 (4.7) and changes in TJC and SJC from BL to 12M were -6.3 (6.6) and -5.9 (5.2), respectively. BL TJC and SJC were not associated with changes in PROs from BL to 12M, whereas changes at 12M in TJC and SJC were significantly (P<0.05) associated with changes in all PROs. Table 2 summarizes the significant (P<0.05) independent associations between BL or change in involvement (tender and/or swollen) of the five available joint groups from BL to 12M with changes in PROs at 12M. Change in hand involvement was significantly associated with changes in all PROs. After adjusting for all available joint groups, changes in elbow, hand, and knee involvement showed the greatest impact on patient function and activity impairment. Elbow was the only joint whose BL involvement was associated with significantly greater improvements in Pt Pain, PtGA, and functional status through 12M. Conclusion: For the majority of pts, specific joint involvement at BL was resolved by 12M of treatment with abatacept. Changes in PROs at 12M were associated with BL elbow involvement and 12M changes in elbow, hand, and knee involvement. These findings have potential implications for clinical practice and research by guiding the focus of evaluations and therapeutic targets. REFERENCES: [1] Bessette, L. et al. Effectiveness of a treat-to-target strategy in patients with moderate to severely active rheumatoid arthritis treated with abatacept. Arthritis Res Ther25, 183 (2023). https://doi.org:10.1186/s13075-023-03151-2 Acknowledgements: NIL. Disclosure of Interests: Janet Pope consultant: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Gilead, Janssen, Medexus, MSD, Novartis, Pfizer, Roche, Sandoz, Sanofi, Teva and UCB, grant/research support: AbbVie, Bristol Myers Squibb, MSD, Pfizer, Roche, Seattle Genetics and UCB, John Sampalis employee of JSS Medical Research, the contract research organization that managed the study, Boulos Haraoui advisory board member and research grants from Abbvie, Amgen, BMS, Fresenius Kabi, Lilly, Pfizer and UCB, Emmanouil Rampakakis employee of JSS Medical Research, the contract research organization that managed the study, Fiona Allum employee of JSS Medical Research, the contract research organization that managed the study, Marc Olivier Trepanier Employee of Bristol Myers Squibb and may hold stock or stock options, Employee of Bristol Myers Squibb, Louis Bessette speaker for Amgen, BMS, Janssen, UCB, AbbVie, Pfizer, Lilly, Novartis, Sanofi, Sandoz, Fresenius Kabi, Teva, Organon and JAMP Pharma, consultant for AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Gilead, Janssen, Medexus, MSD, Novartis, Pfizer, Roche, Sandoz, Sanofi, Teva and UCB.

Background To explore the trajectory of, and factors contributing to, achievement of individual criteria of minimal disease activity (MDA) in patients with active psoriatic arthritis (PsA) treated with guselkumab. Methods The Phase 3, randomized, placebo-controlled DISCOVER-2 study enrolled adults ( N = 739) with active PsA despite standard therapies who were biologic/Janus kinase inhibitor-naive. Patients were randomized 1:1:1 to guselkumab 100 mg every 4 weeks; guselkumab 100 mg at week 0, week 4, then every 8 weeks; or placebo. In this post hoc analysis, patients randomized to guselkumab were included and pooled ( N = 493). Longitudinal trajectories of achieving each MDA criterion through week 100 were derived using non-responder imputation. Time to achieve each criterion was estimated with Kaplan-Meier analysis. Multivariate regression for time to achieve each criterion (Cox regression) and achievement at week 100 (logistic regression) was used to identify contributing factors. Results Continuous improvement across all MDA domains was shown over time. ~70% of patients achieved near remission in swollen joint count (SJC), Psoriasis Area and Severity Index (PASI), and enthesitis through week 100. Median times to achieve individual criteria differed significantly ( p < 0.0001), with SJC ≤ 1 (20 weeks), PASI ≤ 1 (16 weeks), and ≤ 1 tender entheses (16 weeks) being faster than patient-reported criteria (pain ≤ 15 mm, patient global assessment of arthritis and psoriasis ≤ 20 mm, Health Assessment Questionnaire-Disability Index ≤ 0.5) and tender joint count ≤ 1. Higher baseline domain scores, older age, worse fatigue, and increased body mass index were significant predictors of longer time to achieve minimal levels of disease activity assessed via patient-reported criteria. Conclusions Substantial proportions of guselkumab-treated patients achieved individual MDA criteria, each showing continuous improvement through week 100, although with distinct trajectories. Median times to achieve physician-assessed MDA criteria were significantly faster compared with patient-driven criteria. Identification of modifiable factors affecting the time to achieve patient-reported criteria has the potential to optimize the achievement and sustainability of MDA in the clinic via a multidisciplinary approach to managing PsA, involving both medical and lifestyle interventions. Trial registration number NCT03158285. Trial registration date May 16, 2017.

Background: Late-onset psoriatic arthritis (PsA) may be associated with elevated acute phase reactants, higher joint count, and erosive disease at diagnosis.[1,2] Given potential phenotype differences and increasing prevalence with aging populations, it is important to establish the efficacy of current treatments in late-onset PsA. Previous analyses of DISCOVER-1&2 (D1&2) have shown the fully human IL-23p19-subunit inhibitor guselkumab (GUS) to be associated with robust and sustained improvement in PsA signs/symptoms over 52 weeks (W) in subgroups of patients (pts) across a variety of baseline (BL) characteristics.[3] Objectives: To conduct post hoc analyses comparing early- vs. late-onset PsA and evaluate GUS efficacy through W52 in both subgroups. Methods: Adults in D1&2 (90% bio-naive) with active PsA despite standard therapies were randomized 1:1:1 to GUS 100 mg every 4 weeks (Q4W); GUS 100 mg at W0, W4, Q8W; or placebo (PBO) with crossover to GUS 100 mg Q4W at W24. The tertile (T) distribution of age at PsA diagnosis in the pooled D1&D2 population informed the definition of early- (T1<36 years) and late- (T3≥47 years) onset. W24/52 efficacy assessments included least-square mean changes in Disease Activity Index for PsA (DAPSA), swollen/tender joint counts (SJC/TJC), Psoriasis Area Severity Index (PASI; in pts with body surface area ≥3% and Investigator’s Global Assessment ≥2 at BL), C-reactive protein (CRP), pt-reported pain (Pt-Pain), pt global assessment of arthritis and psoriasis (PtGA), Short Form 36-item physical component summary score (SF-36 PCS), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI; in pts with axial involvement [axPsA]), and Ankylosing Spondylitis Disease Activity Score (ASDAS; in pts with axPsA), as well as American College of Rheumatology (ACR) and Minimal Disease Activity (MDA) response rates (employing non-responder imputation for missing data). Results: Relative to pts with late-onset (n=384), those with early-onset (n=376) PsA were significantly younger at BL but had longer PsA duration and a shorter interval between psoriasis and PsA diagnoses (Table 1). The two subgroups had generally comparable joint and skin disease severity at BL, although those with early-onset PsA were more likely to have axPsA and dactylitis, and exhibited higher CRP levels, PtGA, BASDAI and ASDAS. Irrespective of PsA onset age, GUS Q4W or Q8W was associated with significantly (nominal p<0.001) greater improvements in DAPSA, PASI, PtGA, CRP, ASDAS (Figure 1A), SJC, TJC, Pt-Pain, BASDAI, and SF-36 PCS (data not shown), and higher ACR20/50/70 and MDA response rates vs. PBO at W24 (Figure 1B). Further improvements/increased response rates were generally seen through W52 of GUS across early- and late-onset subgroups (Figure 1A, B). Conclusion: Results of post hoc analyses, conducted in a large cohort of mainly bio-naïve pts with active PsA from D1&2, suggest early-onset PsA may be associated with more aggressive presentation several years post-diagnosis. Irrespective of age of PsA onset and differences in baseline profile, however, GUS was associated with significant and clinically meaningful improvements across key PsA domains, with further enhancements generally seen through W52 REFERENCES: [1] Fragoulis GE. J Rheumatol 2022;49:1085[2] Polachek A. Semin Arthritis Rheum 2019;48:834[3] Ritchlin CT. RMD Open 2022;8:e002195 Acknowledgements: NIL. Disclosure of Interests: Enrique R. Soriano AbbVie, Amgen, Bristol Myers Squibb, Eli Lilly, Janssen, Novartis, Pfizer, Roche, and UCB, AbbVie, Janssen, Novartis, and Roche; grant/research support from AbbVie, Janssen, Novartis, Pfizer, Roche, and UCB, Mitsumasa Kishimoto AbbVie, Amgen, Asahi-Kasei Pharma, Astellas, Ayumi Pharma, Bristol Myers Squibb, Chugai, Daiichi-Sankyo, Eisai, Eli Lilly, Gilead, Janssen, Novartis, Pfizer, Tanabe-Mitsubishi, and UCB Pharma., AbbVie, Amgen, Asahi-Kasei Pharma, Astellas, Ayumi Pharma, Bristol Myers Squibb, Chugai, Daiichi-Sankyo, Eisai, Eli Lilly, Gilead, Janssen, Novartis, Pfizer, Tanabe-Mitsubishi, and UCB Pharma., Emmanouil Rampakakis JSS Medical Research, Janssen, Francois Nantel Johnson & Johnson, Janssen, May Shawi Johnson & Johnson, Janssen Research & Development, LLC, Frédéric Lavie Johnson & Johnson, Immunology Global Medical Affairs, Janssen Pharmaceutical Companies, Philip J. Mease AbbVie, Acelyrin, Aclaris, Amgen, BMS, Eli Lilly, Galapagos, Gilead, Inmagene, Janssen, Moonlake Pharma, Novartis, Pfizer, SUN Pharma, UCB, Ventyx, and Xinthera, AbbVie, Acelyrin, Aclaris, Amgen, BMS, Eli Lilly, Galapagos, Gilead, Inmagene, Janssen, Moonlake Pharma, Novartis, Pfizer, SUN Pharma, UCB, Ventyx, and Xinthera, AbbVie, Acelyrin, Aclaris, Amgen, BMS, Eli Lilly, Galapagos, Gilead, Inmagene, Janssen, Moonlake Pharma, Novartis, Pfizer, SUN Pharma, UCB, Ventyx, and Xinthera, Dafna D. Gladman AbbVie, Amgen, Bristol Myers Squibb, Celgene, Eli Lilly, Galapagos, Gilead, Janssen, Novartis, Pfizer, and UCB, AbbVie, Amgen, Bristol Myers Squibb, Celgene, Eli Lilly, Janssen, Novartis, Pfizer, and UCB.