Year Of Treatment In Patients Research Articles

S1448 Impact of Prior Biologic Exposure on the Durability of Ozanimod Over 5 Years of Continuous Treatment in Patients With Ulcerative Colitis: An Interim Analysis of the True North Open-Label Extension Study

S1448 Impact of Prior Biologic Exposure on the Durability of Ozanimod Over 5 Years of Continuous Treatment in Patients With Ulcerative Colitis: An Interim Analysis of the True North Open-Label Extension Study

52676 Safety and efficacy over one year of spesolimab treatment in patients with hidradenitis suppurativa (HS): Interim analysis of an open-label extension (OLE) study

52676 Safety and efficacy over one year of spesolimab treatment in patients with hidradenitis suppurativa (HS): Interim analysis of an open-label extension (OLE) study

Benefits Over Five Years of Ixekizumab Treatment in Patients With Psoriasis Involving Challenging Body Areas.

Psoriasis involving challenging body areas, such as the scalp, face, palmoplantar surfaces, or nails, can be challenging to treat and negatively affects patient outcomes. To assess clear responses and cumulative clinical benefits over 5 years of ixekizumab treatment of moderate-to-severe plaque psoriasis in patients with and without baseline involvement of challenging body areas. This post hoc analysis included patients treated with ixekizumab in the UNCOVER-3 trial. We assessed PASI100 responses through the week (W) 264 and cumulative clinical benefits at W264 (calculated as least-squares mean of the percentage of maximum area under the curve for PASI100 and PASI% improvement and expressed as cumulative clearance days). Statistical differences were calculated via ANCOVA. A total of 385 patients were analyzed: 349 with scalp involvement, 152 with facial involvement, 96 with palmoplantar involvement, and 229 with nail involvement. Proportions of patients achieving PASI100 were numerically similar between patients with and without scalp and nail involvement. More patients without facial and palmoplantar involvement achieved PASI100 at W60 (only palmoplantar), W108, W156, W204, and W264 (only palmoplantar). At W264, cumulative clinical benefits for PASI100 and PASI% improvement were high and similar in both patient groups, with and without challenging body areas. A significant difference (P=0.006) was only observed for PASI% improvement between patients with and without nail involvement. For most efficacy measures, patients treated with ixekizumab over 5 years achieved similar clear responses and cumulative clinical benefits regardless of baseline involvement of challenging body areas. J Drugs Dermatol. 2024;23(8):619-625.  doi:10.36849/JDD.8160.

One-year Efficacy and Safety of Dulaglutide in Patients with Type 2 Diabetes and Chronic Kidney Disease: A Retrospective Study of Asian Patients

PurposeDulaglutide is a long-acting glucagon-like peptide-1 receptor agonist that is not cleared by the kidneys and has proven efficacy and safety in patients with diabetic kidney disease. We aimed to evaluate the 1-year efficacy of dulaglutide in patients with diabetic kidney disease who have used the drug for more than 1 year. MethodsThis retrospective, observational study comprised 131 patients with an estimated glomerular filtration rate (eGFR) of less than 60 mL/min/1.73 m2 who had received dulaglutide for more than one year between June 2016 and May 2023. The primary outcome measures were changes in glycosylated hemoglobin A1c (HbA1c), fasting plasma glucose (FPG), and body weight from baseline to the 12-month follow-up, with assessments performed at six-month intervals. Subgroup analyses were conducted based on age, sex, baseline body mass index, FPG, and HbA1c, and insulin administration at baseline and last follow-up. FindingsThe mean age was 60.0 ± 10.2 years, and 61.1% of the participants were males. Baseline HbA1c, FPG, and body weight were 9.1% (76.0 mmol/mol), 186.8 mg/dL, and 79.3 kg, respectively. Dulaglutide significantly reduced HbA1c, FPG, and body weight from baseline to the 12-month follow-up (mean ± standard error: –1.2 ± 0.1%, –34.8 ± 6.9 mg/dL, and –2.3 ± 0.5 kg, respectively; P < 0.001). Subgroup analysis revealed significant differences in HbA1c reduction based on baseline HbA1c. ImplicationsDulaglutide exhibited sustained glucose-lowering and weight-reduction effects during the initial 1 year of treatment in patients with diabetic kidney disease. Altogether, dulaglutide could serve as a favorable long-term therapeutic option for patients with diabetic kidney disease in real-world clinical settings.

Improvement of bone mineral density and new vertebral fractures during 8 years of TNF-α inhibition in patients with axial spondyloarthritis

ObjectiveIn our prospective cohort with standardized bi-annual measurements of bone mineral density (BMD) and spinal radiographs, we evaluated the long-term course of BMD and the development of radiographic vertebral fractures (VFs) during 8 years of TNFi treatment in patients with radiographic axial spondyloarthritis (r-axSpA). MethodsConsecutive axSpA patients from the GLAS cohort receiving TNFi for ≥8 years were included. Patients who received anti-osteoporotic treatment were excluded. Lumbar spine (LS) BMD was assessed at baseline, 1 year and bi-annually using DEXA. Radiographic VFs were evaluated using the Genant classification. Results126 axSpA patients were included; 75 % male, mean age 42 ± 11 years, ASDAS 3.8 ± 0.8, median LS BMD Z-score -0.5 (IQR -1.4–0.7) and 20 % had radiographic VFs at baseline. Disease activity improved rapidly and sustained. LS BMD Z-score improved significantly up to 4 years compared to the previous time point and sustained thereafter. Median percentage of improvement compared to baseline was 8.9 % (2.8–15.8) and 7.2 % (2.2–14.7) after 4 and 8 years, respectively. Of 90 patients with baseline and 8-year radiographs, 14 (16 %) developed new VFs and 5 (6 %) showed an increase in severity of existing VFs. Of all 44 VFs present at 8 years, 30 % were grade 2 (n = 12) or grade 3 (n = 1). ConclusionIn r-axSpA patients treated with TNFi for 8 years, LS BMD Z-score increased significantly, especially during the first 4 year of treatment. Radiographic VFs continued to develop or progressed, irrespective of improvement in BMD. Therefore, clinical attention for trabecular bone loss is important in daily clinical practice.

Modelling long-term outcomes for patients with systemic lupus erythematosus

BackgroundNew treatments for systemic lupus erythematosus (SLE) aim to improve tolerability and disease activity control over standard of care (SoC) treatment. SoC typically includes daily glucocorticoid (GC) which carries a risk of organ damage over time. This study sought to develop natural history models to identify predictors of long-term outcomes with current SoC SLE treatment. MethodsGeneralized linear and parametric accelerated failure time survival models (GLM) and parametric accelerated failure time (AFT) survival models were designed to identify predictors of disease activity, flare rate, GC use, organ damage, and mortality beyond the first year of treatment in patients with SLE. Models were run using a longitudinal retrospective analysis of prospectively collected Toronto Lupus Cohort (TLC) study data, collected between 1997 and 2020. Covariates of clinical and statistical significance were selected by bivariate- then multi-variate regression to find the model of best fit. FindingsOf the 1255 subjects included, 89 % were female 89 % and 65 % Caucasian. Mean follow-up was 10·5 years. At first visit, 51 % of patients had moderate-to-severe disease activity (SLEDAI-2 K score ≥ 6). Mean organ damage scores gradually increased over the years following diagnosis. Median survival of the cohort was ∼35 years from study entry. In the GLM models, SLEDAI-2 K yearly average, and average GC dose were key for predicting change in SLEDAI-2 K, GC use/ dose, and flare (any/rate). Together, adjusted mean SLEDAI-2 K and GC dose were shown to be predictors of mortality and damage in at least 9 of 12 organ systems considered. InterpretationThese comprehensive, longitudinal, predictive models show that disease activity and GC use are significant predictors of organ damage and mortality in a patient population with predominantly moderate to severe SLE. This deepens understanding of SLE natural history and underscores the need for new treatment approaches that reduce disease activity and GC use with an aim to improve long-term SLE outcomes. FundingThis study was funded by AstraZeneca.

Long-Term Effectiveness of Anti-IL-4R Therapy Following Suboptimal Response to Anti-IL-5/5R Therapy in Severe Eosinophilic Asthma

Dupilumab is an anti-IL-4R monoclonal antibody (mAb) with proven efficacy in severe eosinophilic asthma (SEA). A suboptimal response to anti-IL-5/5R mAbs is seen in some patients with ongoing evidence of type 2 (T2) inflammation. To understand whether targeting IL-13 pathways with dupilumab in these patients may lead to better clinical outcomes. We performed a retrospective analysis of the extended clinical effectiveness of dupilumab up to 2 years of treatment in patients with SEA who had not responded adequately to anti-IL-5/5R biologics. The ability to achieve clinical remission and the change in the remission domains of exacerbation rate (AER), maintenance oral corticosteroid dose (mOCS), lung function (forced expiratory volume in 1 second), and asthma control (Asthma Control Questionnaire 6) were recorded. Thirty-seven patients (mean age 41 years, 70% female) were included in the analysis. The mean (standard deviation) AER fell by almost 90% from 3.16 (1.28) at dupilumab initiation to 0.35 (0.72) after 1 year. The median (interquartile range) mOCS dose (n= 20) fell from 10 (5-25) mg to 0 (0-5) mg at 1 year, with 14 of 20 (70%) able to stop prednisolone altogether. Clinical remission was achieved in 16 of 37 (43%). Patients who achieved remission had a higher pre-IL-5/5R fractional exhaled nitric oxide (FeNO) level (85 [39-198] parts per billion [ppb] vs 75 [42-96] ppb, P= .03). Significant improvements in clinical outcomes are possible after a switch to dupilumab in patients experiencing a suboptimal response to anti-IL-5/5R therapies. A higher FeNO in poor responders to anti-IL-5/5R who achieve remission with dupilumab is suggestive of an IL-13-driven subphenotype of T2-high asthma in which the eosinophil appears unlikely to play a key role in the disease pathogenesis.

Brain Age Is Associated with Cognitive Outcomes of Cholinesterase Inhibitor Treatment in Patients with Mild Cognitive Impairment.

The effect of cholinesterase inhibitor (ChEI) on mild cognitive impairment (MCI) is controversial. Brain age has been shown to predict Alzheimer's disease conversion from MCI. The study aimed to show that brain age is related to cognitive outcomes of ChEI treatment in MCI. Brain MRI, the Clinical Dementia Rating (CDR) and Mini-Mental State Exam (MMSE) scores were retrospectively retrieved from a ChEI treatment database. Patients who presented baseline CDR of 0.5 and received ChEI treatment for at least 2 years were selected. Patients with stationary or improved cognition as verified by the CDR and MMSE were categorized to the ChEI-responsive group, and those with worsened cognition were assigned to the ChEI-unresponsive group. A gray matter brain age model was built with a machine learning algorithm by training T1-weighted MRI data of 362 healthy participants. The model was applied to each patient to compute predicted age difference (PAD), i.e. the difference between brain age and chronological age. The PADs were compared between the two groups. 58 patients were found to fit the ChEI-responsive criteria in the patient data, and 58 matched patients that fit the ChEI-unresponsive criteria were compared. ChEI-unresponsive patients showed significantly larger PAD than ChEI-responsive patients (8.44±8.78 years versus 3.87±9.02 years, p = 0.0067). Gray matter brain age is associated with cognitive outcomes after 2 years of ChEI treatment in patients with the CDR of 0.5. It might facilitate the clinical trials of novel therapeutics for MCI.

P985 Efficacy and safety of de-escalation from 50 mg to 25 mg of oral, once-daily, obefazimod for the third and fifth year of open-label maintenance treatment in patients with moderately to severely active ulcerative colitis (UC): An interim analysis

Abstract Background Obefazimod is an investigational, oral, once-daily, small molecule which enhances expression of microRNA-124 and is currently in phase 3 clinical trials for the treatment of patients with ulcerative colitis (UC) [1]. Obefazimod demonstrated efficacy and safety in patients with UC at week-8 in a Phase 2a and Phase 2b, double-blind, placebo-controlled induction trials [2] and their subsequent open-label maintenance (OLM) studies [3]. Methods Patients with UC who received 50 mg of oral, once-daily, obefazimod for approximately four years in the Phase 2a OLM study and approximately two years in the Phase 2b OLM study, provided they met the eligibility criteria (Mayo Endoscopic subscore = 0 or 1), were given the option to transition to a subsequent open-label maintenance study in which they were administered a daily dose of 25 mg of obefazimod for up to 2 years. This interim analysis, conducted with cut-off date of July 31, 2023, reports the findings of a cohort of patients who completed their week 48 visit. Results As of the cut-off date, there were 71 eligible patients, of whom 8 (11%) discontinued prior to week 48 and 63 (89%) completed their 48-week visit. An as observed analysis indicated a disease control rate of 84% (defined as a stable or improved Modified Mayo Score) (Table 1). The levels of fecal calprotectin were &amp;lt;250 and &amp;lt;150 µg/g for 93% (42/45) and 82% (37/45) of patients with available FCP values, respectively. In total, 39/76 subjects (51.3%) reported at least one treatment emergent adverse event (TEAE). The most frequent TEAEs (≥ 5%) were COVID-19 (7.9%) and ulcerative colitis (6.6%). No new safety findings were identified over these 48 weeks. Conclusion One year after dose de-escalation to a daily regimen of 25 mg of obefazimod, favorable outcomes in disease control were observed among patients with UC who demonstrated endoscopic improvement (ES&amp;lt;1) after 2-4 years of 50 mg od. No new safety signals have emerged for a duration of up to five years of treatment with once-daily obefazimod.

Safety Analyses of the Phase 3 VISION Trial of [177Lu]Lu-PSMA-617 in Patients with Metastatic Castration-resistant Prostate Cancer

Background and objective[177Lu]Lu-PSMA-617 (177Lu-PSMA-617) plus the standard of care (SoC) significantly improved overall survival and radiographic progression-free survival versus SoC alone in patients with prostate-specific membrane antigen (PSMA)-positive metastatic castration-resistant prostate cancer in the VISION trial. We evaluated the safety of additional cycles of 177Lu-PSMA-617 and the impact of longer observation time for patients receiving 177Lu-PSMA-617 plus SoC. MethodsVISION was an international, open-label study. Patients were randomised 2:1 to receive 177Lu-PSMA-617 plus SoC or SoC alone. The incidence of treatment-emergent adverse events (TEAEs) was assessed in prespecified subgroups of patients who received ≤4 cycles versus 5–6 cycles of treatment and during each cycle of treatment. The TEAE incidence was also adjusted for treatment exposure to calculate the incidence per 100 patient-treatment years of observation. This analysis was performed for the first occurrence of TEAEs. Key findings and limitationsThe any-grade TEAE incidence was similar in cycles 1–4 and cycles 5–6. TEAE frequency was similar across all cycles of 177Lu-PSMA-617 treatment. No additional safety concerns were reported for patients who received >4 cycles. The exposure-adjusted safety analysis revealed that the overall TEAE incidence was similar between arms, but distinct trends for different TEAE types were noted and the incidence of events associated with 177Lu-PSMA-617 remained higher in the 177Lu-PSMA-617 arm. Conclusions and clinical implicationsLonger exposure to 177Lu-PSMA-617 plus SoC was not associated with a higher toxicity risk, and the extended time for safety observation could account for the higher TEAE incidence in comparison to SoC alone. The findings support a favourable benefit-risk profile for 6 cycles of 177Lu-PSMA-617 in this setting and the use of up to 6 cycles of 177Lu-PSMA-617 in patients who are clinically benefiting from and tolerating this therapy. Patient summaryFor patients with metastatic prostate cancer no longer responding to hormone therapy, an increase in the number of cycles of treatment with a radioactive compound called 177Lu-PSMA-617 from four to six had no additional adverse side effects.

Effects of tafamidis on the left ventricular and left atrial strain in patients with wild-type transthyretin cardiac amyloidosis.

Although tafamidis is used in patients with wild-type transthyretin cardiac amyloidosis (ATTRwt-CA), its specific effect on cardiac function is unclear. Thus, this study aimed to investigate the effect of tafamidis on left atrial (LA) and left ventricular function using speckle-tracking echocardiography for 1 year of treatment in patients with ATTRwt-CA. We included 23 patients (mean age, 76 years) with ATTRwt-CA confirmed via biopsy. We analysed the left ventricular and LA strain using 2D speckle-tracking echocardiography and compared these parameters before and 1 year after starting treatment with tafamidis between 16 patients with sinus rhythm (SR) and 7 patients with atrial fibrillation (AF). In ATTRwt-CA patients with SR, LA reservoir strain significantly improved by 1-year tafamidis treatment (10.5 ± 5.0% to 11.9 ± 5.3%, P = 0.0307) although global longitudinal strain (GLS) did not (-10.6 ± 3.1% to -11.3 ± 3.0%, P = 0.0608). In contrast, LA reservoir strain was not significantly changed (5.4 ± 2.9% to 4.9 ± 1.7%, P = 0.4571), and GLS deteriorated (-8.4 ± 2.3% to -6.8 ± 1.4%, P = 0.0267) in ATTRwt-CA patients with AF. LA function improved with tafamidis treatment in ATTRwt-CA patients with SR but not left ventricular function. However, these cardiac functions did not improve with tafamidis treatment in ATTRwt-CA patients with AF.

The Effect of Two Years of Secukinumab Treatment on Bone Metabolism in Patients with Radiographic Axial Spondyloarthritis: Results from Daily Clinical Practice.

Our objective was to explore bone-related outcome and bone turnover markers (BTM) during 2 years of secukinumab treatment in patients with radiographic axial spondyloarthritis (r-axSpA) in daily clinical practice. Included were consecutive r-axSpA outpatients from the Groningen Leeuwarden axSpA (GLAS) cohort treated with secukinumab for 2 years. At baseline and 2 years, spinal radiographic damage was assessed using the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS; 0-72), cervical facet joint involvement according the "de Vlam" scoring method (0-15) and radiographic vertebral fractures (VF) using the "Genant" method (grade 0-3). At all visits, BTM reflecting collagen resorption (serum type I collagen C-telopeptide; sCTX), collagen formation (procollagen type 1 N-terminal peptide; PINP) and bone mineralization (bone-specific alkaline phosphatase; BALP) were measured and expressed in Z-scores to correct for the normal influence of age and gender. 17 r-axSpA patients were included; 53% male, mean age was 47±15 years, mean Ankylosing Spondylitis Disease Activity Score (ASDAS) 3.9±1.2, and 53% was biological naïve. The median 2-year progression rates were 1.1 for mSASSS and 0.5 for facet joints, which was less than the smallest detectable change. One traumatic VF (grade 3) occurred. Serum levels of sCTX and PINP remained stable during secukinumab treatment and BALP decreased significantly after 2 years, with median 0-2 year change in Z-scores of +0.1, -0.4, and -1.2, respectively. This explorative study of r-axSpA patients treated with secukinumab in daily clinical practice showed low radiographic spinal progression during 2 years of follow-up. Collagen resorption and formation markers remained stable, whereas mineralization marker BALP decreased significantly after 2 years. Our results are in line with the results of in vitro studies demonstrating that inhibition of IL17-A resulted in suppression of osteogenic differentiation with significant decrease in mineralization.

Efficacy and Safety of Subcutaneous Ravulizumab in Patients with Paroxysmal Nocturnal Hemoglobinuria Who Received Prior Intravenous Eculizumab: 2-Year Follow-up

Background : Subcutaneous (SUBQ) ravulizumab, administered weekly via an on-body delivery system, showed pharmacokinetic (PK) non-inferiority to intravenous (IV) ravulizumab over 71 days in adult patients with paroxysmal nocturnal hemoglobinuria (PNH) who were clinically stable on prior IV eculizumab treatment (NCT03748823). This analysis reports results through 2 years of SUBQ ravulizumab treatment during the extension period of a phase 3 randomized trial. The reporting period started at day 15 for patients who continued SUBQ ravulizumab during the extension period (SUBQ/SUBQ) and day 71 for patients who switched from IV ravulizumab to SUBQ ravulizumab (IV/SUBQ). Objectives: To evaluate the PK, pharmacodynamics (PD), efficacy, and safety of SUBQ ravulizumab through 2 years (day 743) of treatment in adult patients with PNH previously treated with IV eculizumab. Methods: Patients (≥ 18 years) who received IV eculizumab (once every 2 weeks) for at least 3 months prior to study entry with clinically stable PNH (lactate dehydrogenase [LDH] levels ≤ 1.5 × upper limit of normal [246 U/L]) were enrolled in the study, which consisted of a screening period (day −1 to day −30), a 10-week randomized treatment period, and an extension period of up to 172 weeks. During the randomized treatment period, patients were assigned (2:1) to receive either SUBQ ravulizumab (weekly) or IV ravulizumab (once every 8 weeks); all patients received SUBQ ravulizumab during the extension period. PK/PD endpoints through 2 years of treatment included serum ravulizumab and free C5 concentrations. Efficacy endpoints included change in LDH from baseline, incidence of breakthrough intravascular hemolysis (BTH), maintenance of transfusion avoidance, and maintenance of stabilized hemoglobin (avoidance of a ≥ 2 g/dL decrease in hemoglobin in the absence of transfusion). Fatigue was assessed using the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue subscale questionnaire. Safety outcomes, including adverse events (AEs), serious AEs (SAEs), and adverse device effects (ADEs), were also assessed up to the 2-year data cut-off. Results: In total, 128 patients received SUBQ ravulizumab (SUBQ/SUBQ: n = 84; IV/SUBQ: n = 44; mean [range] duration of SUBQ treatment: 839.4 [37 - 1108] days). During 2 years of SUBQ treatment, serum ravulizumab concentrations were maintained ≥ 175 μg/mL and serum free C5 concentrations &amp;lt; 0.5 μg/mL, the previously defined thresholds for achieving and sustaining complete terminal complement inhibition ( Figure). Efficacy endpoints remained consistent over time. Mean (standard deviation [SD]) percentage change in LDH from baseline to day 743 was +2.3% (21.6%; n = 108). BTH events were infrequent: 5/128 patients (3.9%). Transfusion avoidance was maintained in 74.2% of patients (n = 95/128) and 69.1% (n = 85/123) achieved stabilized hemoglobin. Mean (SD) change in FACIT-Fatigue subscale score from baseline to day 743 was +1.3 (9.09; n = 68). The most common AEs (excluding ADEs related to device product issues) during SUBQ treatment were COVID-19 (25.0%), headache (18.8%), and pyrexia (18.0%). Treatment-emergent SAEs were experienced by 29.7% of patients. No treatment-emergent anti-drug antibodies were observed. ADEs not related to a medical device issue were reported by 25.0% of patients. The most frequently reported ADEs unrelated to a medical device issue were injection site reaction (4.7%), medical device site erythema (4.7%), and injection site erythema (3.1%). Among 30,221 devices used in the study, full volume per device was delivered by 98.6% of devices. Complaints were reported in 1.6% of devices used: 0.1% had a confirmed technical defect, 0.8% had a use error, and 0.7% had other/unknown defects. Conclusions: The efficacy of ravulizumab was maintained following the switch from IV to SUBQ ravulizumab and no new safety signals were identified through 2 years of treatment in patients with PNH. SUBQ ravulizumab demonstrated a favorable benefit-risk profile and the types and incidences of AEs were comparable with those reported for IV eculizumab and IV ravulizumab in previous studies, except for local site reactions. The SUBQ method of administration provides an additional treatment choice for patients with PNH receiving ravulizumab treatment.

94 Maintenance of efficacy and safety with lebrikizumab up to one year of treatment in patients with moderate-to-severe atopic dermatitis with or without topical corticosteroids

94 Maintenance of efficacy and safety with lebrikizumab up to one year of treatment in patients with moderate-to-severe atopic dermatitis with or without topical corticosteroids

Relationship between vedolizumab serum concentrations in the induction phase and early and sustained response in the first year of treatment in patients with ulcerative colitis

ObjectiveEvidence on the usefulness of proactive monitoring of vedolizumab serum concentrations during the induction phase of treatment is limited. The objective of our study was to evaluate the effectiveness of measuring such concentrations during this phase in predicting response to treatment in patients with ulcerative colitis with a view to determining whether patients would benefit from early monitoring of vedolizumab serum concentrations. MethodThis was a prospective descriptive study carried out at three public general hospitals. It included adult patients with ulcerative colitis who were initiated on vedolizumab at the participating hospitals from June 2019 to June 2020. Vedolizumab serum concentrations were determined at weeks 6 and 14. Response to treatment was biologically, clinically, and endoscopically evaluated at weeks 6, 14, and 52. An analysis was made of the relationship between vedolizumab serum concentrations at week 6 and early response to treatment, and of the relationship between the vedolizumab serum concentrations at weeks 6 and 14 and persistent response at one year. ResultsA total of 45 patients were included of whom 22 (49%) were considered non-responsive after one year and required intensification of treatment. The median (interquartile range) vedolizumab serum concentrations obtained at 6 weeks was higher in patients who obtained an early response and in those who maintained the response at one year than in those who did not respond to vedolizumab [27.4 (19.0-40.8) µg/mL vs 15.6 (13.4-28.5) µg/mL; p = 0.018] and [29.9 (19.2-43.2) µg/mL vs 18.2 (15.4-26.9) µg/mL; p = 0.022] respectively. Vedolizumab serum concentrations ≥ 17.3 µg/mL at week 6 were predictive of a good early response, and vedolizumab serum concentrations ≥ 26.1 µg/mL at week 6 predicted a sustained response at one year. No relationship was found between vedolizumab serum concentrations at week 14 and a sustained response. ConclusionsWe observed a relationship between vedolizumab serum concentrations determined at week 6, and early and maintained response to vedolizumab therapy in patients with ulcerative colitis, which supports early drug monitoring during the induction phase to individualize treatment and increase effectiveness.

THU163 Traffic Light Alerting System For Adherence Risk Management To Improve Catch-Up Growth In Patients Receiving Recombinant Human Growth Hormone Therapy

Abstract Disclosure: S. Loche: Advisory Board Member; Self; SL has received advisory board fees from the healthcare business of Merck KGaA, Darmstadt, Germany. Consulting Fee; Self; SL has received consultancy fees from the healthcare business of Merck KGaA, Darmstadt, Germany. Speaker; Self; SL has received lecture fees from the healthcare business of Merck KGaA, Darmstadt, Germany. P. van Dommelen: Consulting Fee; Self; PvD has a consultancy agreement with the healthcare business of Merck KGaA, Darmstadt, Germany. E. Koledova: Employee; Self; EK is an employee of the healthcare business of Merck KGaA, Darmstadt, Germany. Stock Owner; Self; EK holds shares in the healthcare business of Merck KGaA, Darmstadt, Germany. Background: In our previous study, a data-driven clinical decision support system based on “traffic light” visualizations for adherence risk management in patients receiving recombinant human growth hormone (r-hGH) treatment was developed.1 Two “traffic lights” were most promising: mean adherence and standard deviation (SD) of hours to next injection (administering injections at around the same time each day). We aimed to study the effect of these two adherence-based traffic lights on catch-up growth in the first year of treatment in patients with growth hormone deficiency (GHD) and those born small for gestational age (SGA). Data and Methods: Height and adherence data were extracted from the easypod™ connect ecosystem and taken from the easypod™ connect observational study.2 Patients with: height standard deviation scores (HSDS) of ≤-2 at treatment start; age 2-15 years at treatment start; and ≥1 measurement and adherence data available in the first year of treatment, were selected. Mean adherence was classified as high (≥85%), intermediate (&amp;gt;56%-&amp;lt;85%), or low (≤56%); high (≥15.9 [P95]), intermediate (≥10.1 [P85]), or low (&amp;lt;10.1) were used for SD of hours to next injection. Linear regression analysis was performed with ΔHSDS between treatment start and first year of treatment as dependent variables and the adherence-based values as independent variables, all adjusted for age and HSDS at treatment start. Results: In total, data for 1,045 patients (776 and 269 with GHD and those born SGA, respectively) were available. Only some of the adherence-based categories had a significant and independent effect on ΔHSDS (P=0.004). Adjusted for age and HSDS at treatment start, patients with high/intermediate mean adherence had, on average, a +0.15 SD higher ΔHSDS (P=0.004), while this was +0.09 SD for patients with a low SD of hours to the next injection (P=0.003). Therefore, patients with both high/intermediate mean adherence and a low SD of hours to the next injection had, on average, a +0.24 SD higher ΔHSDS compared with patients with both low mean adherence and a high SD of hours to the next injection. Conclusions: Our research shows that good adherence and administering injections around the same time each day play an essential role in optimizing catch-up growth. Adherence-based traffic lights can alert clinicians to have discussions with patients/caregivers to mitigate the risk of sub-optimal adherence and, consequently, improve catch-up growth.

43795 Effectiveness in real-world practice after one year of Brodalumab treatment for patients with moderate-to-severe psoriasis and effectiveness in obese patients: thirty-three patient cohort

43795 Effectiveness in real-world practice after one year of Brodalumab treatment for patients with moderate-to-severe psoriasis and effectiveness in obese patients: thirty-three patient cohort

Expectations, symptoms, and quality of life before and after 1 year of Pirfenidone treatment in patients with idiopathic pulmonary fibrosis: A single-arm, open-label nonrandomized study.

Antifibrotic therapies reduce lung function decline in patients with idiopathic pulmonary fibrosis (IPF). This single-arm, open-label, nonrandomized study aimed to determine the influence of antifibrotic treatment on patients' reported symptoms and expectations of the therapy. Fifty-two patients with confirmed IPF at a mean age of 65 ± 8.63 years (73% male) completed the following surveys at baseline and after 12 months of Pirfenidone treatment: Short Form Healthy Survey (SF-36), St. George's Respiratory Questionnaire (SGRQ), Baseline Dyspnea Index (BDI), Fatigue Assessment Scale (FAS), Leicester Cough Questionnaire (LCQ), and Patient's Needs and Expectations Authors' Survey. The most important patients' needs were access to novel therapy, fast and easy access to health centers specializing in IPF treatment, and the improvement of the general condition or the maintenance of its level. These needs did not change with time, except for the significantly more important right of deciding on disease management after 12 months of treatment (p = 0.014). The quality of life per SF-36, after 1 year of Pirfenidone treatment, significantly improved in the physical cumulative score (p = 0.004) and mental cumulative score (p = 0.003). Significant deteriorations were observed in bodily pain and vitality. For the remaining questionnaires (SGRQ, BDI, FAS, and LCQ), no significant changes in the course of the study were noticed. Around one in 10 patients subjected to Pirfenidone therapy had achieved general symptom improvement in all areas; that is, quality of life improvement as well as cough and dyspnea reduction. One year of antifibrotic treatment resulted in a general improvement in the quality of life per the SF-36 questionnaire. Patients' expectations of disease management did not change; also, access to novel therapies and easy access to health centers specializing in IPF management remained their top needs.

P98 Real-world effectiveness of guselkumab in absolute Psoriasis Area and Severity Index-stratified patients with psoriasis: data from the British Association of Dermatologists Biologics and Immunomodulators Register

Abstract Guselkumab is a fully human monoclonal antibody that inhibits interleukin-23 by selectively targeting the p19 subunit. Long-term evaluations have demonstrated high levels of clinical response and improvement in patient-reported outcomes over 5 years of guselkumab treatment in patients with psoriasis. Psoriasis has a significant and negative impact on a patient’s quality of life, even among patients with a Psoriasis Area and Severity Index (PASI) score &amp;lt; 10. Both absolute PASI (aPASI) and the Dermatology Life Quality Index (DLQI) are widely used tools to assess disease impact, as well as treatment eligibility and response. This retrospective analysis evaluated the impact of guselkumab treatment over 1 year across aPASI-stratified patients with psoriasis in BADBIR, a national pharmacovigilance registry documenting longitudinal clinical data for individuals with psoriasis initiating systemic therapies. Retrospective analyses of the guselkumab cohort were carried out using BADBIR data collected up to September 2021. Data were analysed for patients who had initiated guselkumab treatment and had recorded aPASI and DLQI assessments at both baseline and the 12-month follow-up. Patients were stratified according to psoriasis severity at baseline: aPASI &amp;lt; 5, aPASI ≥ 5 to ≤ 10 and aPASI &amp;gt; 10 disease. Treatment effect was defined as the mean improvement in DLQI and aPASI scores for the overall group of guselkumab-treated patients and for subsets of patients with aPASI &amp;lt; 5, aPASI ≥ 5 to ≤ 10 and aPASI &amp;gt; 10 at baseline. Five patients were excluded owing to treatment cessation prior to the 12-month cutoff. Following 12 months of guselkumab treatment, patients with aPASI &amp;lt; 5, aPASI ≥ 5 to ≤ 10 and aPASI &amp;gt; 10 at baseline achieved a mean (SD) DLQI score of 2.18 (5.64), 2.79 (5.15) and 1.80 (3.56), representing a decrease of 62.0%, 74.8% and 89.1% from baseline, respectively. Additionally, patients with aPASI &amp;lt; 5, aPASI ≥ 5 to ≤ 10 and aPASI &amp;gt; 10 at baseline achieved a mean (SD) aPASI score of 0.96 (1.84), 3.16 (3.90) and 2.78 (4.93), representing a decrease of 40%, 58.6% and 84.5% from baseline, respectively. Among patients with an aPASI score &amp;lt; 10 at baseline (n = 53), 83.0% (n = 44) achieved aPASI score ≤ 3; of these, 67.9% (n = 36) achieved an aPASI score ≤ 2 and 54.7% (n = 29) achieved an aPASI score ≤ 1. These data demonstrate that guselkumab produces an effective and consistent response in patients with a broad range of disease severity at baseline, as reflected by mean improvements in aPASI and DLQI. Greater reductions in DLQI and aPASI scores were observed after 12 months of guselkumab treatment in patients with more severe psoriasis at baseline.

Long-Term Efficacy and Safety of Upadacitinib in Patients with Rheumatoid Arthritis: Final Results from the BALANCE-EXTEND Open-Label Extension Study.

Upadacitinib (UPA) is an oral, selective Janus kinase inhibitor that has demonstrated favorable efficacy with an acceptable safety profile across a global, phase 3 program in rheumatoid arthritis (RA). This phase 2 open-label extension investigated the efficacy and safety of UPA through 6years of treatment. Patients from two phase 2b trials (BALANCE-1 and -2) enrolled in BALANCE-EXTEND (NCT02049138) and received open-label UPA 6mg twice daily (BID). Dose increases to 12mg BID were required for patients with < 20% improvement in swollen or tender joint counts at weeks 6 or 12 and permitted for those not achieving Clinical Disease Activity Index (CDAI) low disease activity (LDA; CDAI 2.8 to ≤ 10). Dose reduction to UPA 6mg BID was permitted only for safety or tolerability reasons. After January 2017, the 6/12mg BID doses were replaced by 15/30mg once-daily extended-release equivalents. Efficacy and safety were monitored up to 6years of UPA treatment; outcomes included rates of achievement of LDA or remission. Data were analyzed for patients who received the lower UPA dose throughout; titrated up to the higher UPA dose from weeks 6 or 12; or titrated to the higher UPA dose and back down. Overall, 493 patients entered BALANCE-EXTEND ('Never titrated', n = 306; 'Titrated up', n = 149; 'Titrated up and down', n = 38), and 223 patients (45%) completed the 6-year study. Total cumulative exposure was 1863 patient-years. Rates of LDA and remission were maintained through 6years. Overall, 87%/70%/73% of patients in the 'Never titrated'/'Titrated up'/'Titrated up and down' groups achieved CDAI LDA at week312, while the respective rates of Disease Activity Score28 with C-reactive protein meeting LDA and remission criteria were 85%/69%/70% and 72%/46%/63%. Improvements in patient-reported outcomes were similar among the three groups. No new safety signals were identified. In this open-label extension of two phase 2 studies, UPA demonstrated sustained efficacy and an acceptable safety profile through 6years of treatment in patients who completed the study. These data support a favorable long-term benefit-risk profile of UPA in patients with RA. Trial registration number: NCT02049138.