This study compared real-world overall survival and the risk of physical comorbidities and mental health conditions among patients aged <65 years with versus without inherited retinal diseases (IRDs) in the United States (US). Optum® Electronic Health Record data (January 2014-January 2023) were evaluated for IRD (patients with ≥2 medical visits with an IRD diagnosis; index date: second such medical visit) and non-IRD (patients without an IRD diagnosis; index date: random medical visit) cohorts. Baseline demographics were balanced between cohorts using propensity score matching (2:1). Outcome measures were overall survival (date of death due to any cause) and presence of physical comorbidities and mental health conditions (medical visit with a corresponding diagnosis code). In total, 4594 patients with IRD were matched to 9188 patients without IRD (mean age: 38.7 vs. 38.2 years, 53.9% vs. 55.1% female, mean follow-up: 53.1 vs. 52.8 months). Over 84 months, patients with versus without IRD had a 24% higher risk of death (overall survival: 95.8% vs. 96.7%; hazard ratio: 1.24; 95% confidence interval: 1.00-1.53; p = 0.046) and were at significantly higher risk for each evaluated physical comorbidity and mental health condition (all p < 0.05). The development of novel therapies is thus needed to address the clinical burden of IRD.

Atypical antipsychotics are common adjunctive therapies for major depressive disorder (MDD) with inadequate antidepressant (ADT) response. In 2025, lumateperone was approved in the US as adjunctive treatment for adults with MDD, and comparative evidence is lacking. This network meta-analysis compared the efficacy and safety of lumateperone with those of other approved atypical antipsychotics for MDD. Registrational randomized clinical trials as documented in US product labeling (RCTs; N = 10; aripiprazole, brexpiprazole, cariprazine, lumateperone, and quetiapine XR) were used to build a star-shaped, 11-treatment-dose node network anchored on placebo + ADT. Outcomes available for ≥ 9 RCTs were considered. Efficacy outcomes comprised change from baseline in Montgomery-Åsberg Depression Rating Scale (MADRS), MADRS response and remission, and change from baseline in Clinical Global Impression-Severity (CGI-S) scale. Safety outcomes included weight change from baseline, akathisia, and somnolence. A fixed-effect Bayesian approach was applied. Pairwise treatment effects were compared; a probability of superiority > 85

BACKGROUND:Approximately 17% of patients with non-small cell lung cancer (NSCLC) have epidermal growth factor receptor mutations (EGFRm). Amivantamab received United States Food and Drug Administration approvals in advanced NSCLC for patients with EGFR exon 20 insertions (exon20ins) who progressed after platinum-based chemotherapy (PBC) on 05/21/2021, for first-line (1 L) EGFR exon20ins on 03/01/2024, and for 1 L and second-line or later (2 L+) EGFR exon 19 deletion and L858R on 08/20/2024 and 09/19/2024, respectively. This claims-based study describes real-world treatment patterns and healthcare resource utilization (HRU) among insured patients with advanced NSCLC initiating amivantamab in 2 L or later (2 L+). METHODS:Komodo Research Data closed claims (01/01/2016-10/31/2023) were used to analyze insured adults with a diagnosis of lung cancer who initiated amivantamab on/after 05/21/2021 in 2 L+. Treatment patterns, including prior PBC and immunotherapy (IO) use, were described by line of therapy (LOT). All-cause HRU per-patient-per-month (PPPM) was assessed during the amivantamab LOT and all LOTs preceding amivantamab. Time to next treatment or death (TTNT-D) was reported using Kaplan-Meier analysis for each LOT. RESULTS:Overall, 126 patients initiated amivantamab in 2 L+ (mean age: 60.2 years, 63.5% female). Amivantamab was initiated in 2 L by 51.6% of patients, while 32.5% and 15.9% initiated amivantamab in third-line (3 L) and fourth-line or later (4 L+), respectively. Most patients initiated amivantamab as monotherapy (2 L: 92.3%; 3 L: 73.2%; 4 L+: 80.0%), had prior PBC use (2 L: 83.1%; 3 L: 100.0%; 4 L+: 100.0%), and prior IO use (2 L: 60.0%; 3 L: 63.4%; 4 L+: 85.0%). Mean outpatient service use was 5.87 days PPPM before amivantamab initiation and 6.79 days PPPM during amivantamab treatment. Mean inpatient admissions PPPM were 0.05 before amivantamab and 0.08 during amivantamab treatment. Among patients initiating amivantamab in 2 L, 3 L, or 4 L+, median TTNT-D was 11.0 months, 5.3 months, and 6.1 months, respectively. CONCLUSIONS:Among insured patients with advanced NSCLC receiving amivantamab in 2 L+, TTNT-D aligned with results reported in clinical trials. Before initiating amivantamab, most patients received IO, despite IO use being inconsistent with treatment guidelines and limited demonstrated benefit. HRU was similar before and during amivantamab treatment, suggesting that amivantamab does not contribute to an increase in medical services compared to treatment regimens used in earlier LOTs.

There is limited prior literature comparing long-term treatment persistence between guselkumab and subcutaneous (SC) tumor necrosis factor inhibitors (TNFi) in biologic-naïve and biologic-experienced patients with active psoriatic arthritis (PsA). This study compared on-label persistence through 24 months between patients with active PsA newly initiating guselkumab or SC TNFi. IQVIA PharMetrics® Plus database was used to identify adults with active PsA initiating guselkumab or an SC TNFi (adalimumab or biosimilar, certolizumab pegol, etanercept or biosimilar, SC golimumab) between 07/14/2020 and 12/31/2022 (index date: first treatment claim for one of these medications). Patients were further stratified as biologic-naïve (no pre-index biologic disease-modifying antirheumatic drug [bDMARD] claim) or biologic-experienced (≥ 1 pre-index bDMARD claim). The guselkumab and SC TNFi cohorts were balanced using overlap propensity score weighting. Treatment persistence with on-label therapy (absence of dose modification or therapy exposure gap of twice the duration between consecutive administrations, i.e., 112 days for guselkumab or 56 days for SC TNFi) was estimated using weighted Kaplan–Meier analysis through 24 months. On-label persistence rates were compared between cohorts using weighted Cox proportional hazards models. In the guselkumab cohort (N = 804), 361 (44.9

# Background Approximately 17% of patients with non-small cell lung cancer (NSCLC) have epidermal growth factor receptor-mutated (EGFRm) NSCLC, 84% of which are exon 19 deletions (Ex19del)/exon 21 substitutions (L858R). Unmet needs for patients treated with tyrosine kinase inhibitors (TKIs) for EGFRm (Ex19del/L858R) advanced NSCLC, including osimertinib, are relevant to US population health decision makers. # Objectives To describe healthcare resource utilization (HRU) and costs by line of therapy (LOT) among patients with EGFRm (Ex19del/L858R) advanced NSCLC initiating first-line (1L) treatment. # Methods IBM MarketScan® Research Databases (1/1/2010-1/31/2023) were used to select adult patients with advanced NSCLC initiating an EGFR-TKI during any LOT on/after 4/18/2018 (osimertinib approval; EGFRm Ex19del/L858R proxy). Per-patient-per-month (PPPM) all-cause HRU and costs were described in 1L, second-line (2L), and third-line (3L) overall and among subgroups receiving 1L osimertinib monotherapy or platinum-based chemotherapy (PBC) without immunotherapy, separately. # Results The study included 409 patients with EGFRm advanced NSCLC (mean age, 60.5 years; 70.2% female). In 1L, 72.9% initiated osimertinib-based therapy (2L, 45.9%; 3L, 41.2%), 21.0% initiated chemotherapy (2L, 30.0%; 3L, 36.5%), 4.6% initiated another EGFR-TKI (2L, 12.9%; 3L, 12.9%), and 1.5% initiated immunotherapy (2L, 11.2%; 3L, 9.4%). Overall, 170 patients (41.6%) progressed to 2L among whom 85 (50.0%) progressed to 3L. Mean LOT duration decreased with each successive LOT (1L, 10.2 months; 2L, 8.7 months; 3L, 8.0 months). Across LOTs, patients had a mean of >4 outpatient visits PPPM (1L, 4.79; 2L, 4.26; 3L, 4.40), and the 1L osimertinib monotherapy subgroup (n = 279) had a mean of 0.69 inpatient days PPPM during 1L (2L, 0.82; 3L, 0.74). Mean all-cause costs PPPM were $27 751 in 1L, $28 971 in 2L, and $31 251 in 3L. Among the 1L osimertinib monotherapy subgroup, mean PPPM costs were $27 610 in 1L, $35 501 in 2L, and $36 618 in 3L. Among the 1L PBC subgroup (n = 58), mean PPPM costs were $23 820 in 1L, $24 788 in 2L, and $23 348 in 3L. # Discussion Among patients with EGFRm (Ex19del/L858R) advanced NSCLC initiating 1L, each successive LOT was shorter and more costly. # Conclusions Findings highlight the importance of using the most effective 1L treatments to delay disease progression and reduce HRU and costs.

OBJECTIVE:To describe potential drug-drug interactions (DDIs) with oral advanced therapies among patients with ulcerative colitis (UC) and characterize clinical assessments before ozanimod initiation. METHODS:Adults with UC were selected from the Merative MarketScan Commercial Database (01 January 2018-31 January 2023); the index date was the most recent UC diagnosis. Patients had no other immune conditions in the 12-month baseline period before the index date. Those with moderate-to-severe UC were analyzed separately. Potential baseline DDIs were identified as claims for medications that may cause a moderate/severe DDI with Janus kinase (JAK) inhibitors (tofacitinib/upadacitinib) or ozanimod according to the Merative Micromedex Complete Drug Interactions Tool. Clinical assessments before ozanimod initiation were characterized. RESULTS:Of 58,870 patients with UC, 24,654 (41.9%) had moderate-to-severe UC. All potential DDIs with ozanimod were severe, while JAK inhibitors had moderate and severe potential DDIs. Among patients with UC, mean (standard deviation) number of severe DDIs was 2.0 (2.4) for ozanimod and 0.2 (0.5) for JAK inhibitors; in moderate-to-severe UC, it was 2.3 (2.6) for ozanimod and 0.4 (0.6) for JAK inhibitors. The most common potential DDIs for ozanimod in UC and moderate-to-severe UC were ondansetron (18.6% and 22.7%), azithromycin (11.9% and 12.8%), as well as hydrocodone, fentanyl, albuterol, ciprofloxacin, and metronidazole (9.0%-11.0% each). For JAK inhibitors, these were COVID-19 vaccines (30.7% and 31.4%), infliximab (8.5% and 20.2%), fluconazole (6.1% and 6.8%), and azathioprine (5.5% and 13.0%). Among patients initiating ozanimod, the first claim for a required clinical assessment was on average, 8 months before initiation. CONCLUSION:Comorbidities and polypharmacy among patients with UC pose a high risk of DDIs for oral advanced therapies and required pre-treatment clinical assessments can be complicated. This justifies a thorough review of patient profiles for prescribers considering novel treatment options.

e20646 Background: Among patients with non-small cell lung cancer (NSCLC), ~19-24% harbor epidermal growth factor receptor mutations (EGFRm). Amivantamab (AMI) was approved by the US Food and Drug Administration on 5/21/2021 for second-line (2L) patients with EGFR exon 20 insertions (Exon20Ins) advanced NSCLC who progressed after platinum-based chemotherapy (PBC), on 3/1/2024 for first-line (1L) EGFR Exon20Ins, and for 1L (8/20/2024) and 2L (9/19/2024) EGFR exon 19 deletion and L858R. Immunotherapy (IO) monotherapy (mono) has limited effectiveness in treating EGFRm advanced NSCLC and fails to add clinical benefit when used with PBC, yet increases toxicity risk. This study evaluates real-world treatment patterns and outcomes among patients receiving AMI. Methods: Komodo Research Data closed claims (1/1/2016-10/31/2023) were used to analyze adults with a lung cancer diagnosis (ICD-10-CM: C34) initiated on AMI on/after 5/21/2021 in 2L or later (2L+) for advanced NSCLC. Baseline brain/cerebral meninges (CNS) metastases were identified based on ≥1 diagnosis (ICD-10-CM: C79.3) in the continuous eligibility period before 1L initiation. Treatment patterns, including prior IO use with/without PBC, were described for patients initiating AMI in 2L, third-line (3L), and fourth-or-later line (4L+). Time to next treatment or death (TTNT-D) was evaluated for patients initiating AMI mono in 2L after PBC using Kaplan-Meier survival analysis. Results: A total of 126 patients initiated AMI in 2L+ (mean age: 60.2 years; 63.5% female), with 65 (51.6%) receiving AMI in 2L, 41 (32.5%) in 3L, and 20 (15.9%) in 4L+. Baseline CNS metastases were observed in 35.4% of 2L AMI patients (3L: 22.0%; 4L+: 35.0%). For patients initiating AMI in 2L, median follow-up duration was 6.5 months (3L: 5.9; 4L+: 6.8) [Table 1]. AMI mono was used in 92.3% of 2L patients (3L: 73.2%; 4L+: 80.0%). In combination therapy, AMI with osimertinib was most commonly used (2L: 4.6%, 3L: 19.5%; 4L+: 15.0%). Prior PBC use was observed in 83.1% of 2L AMI patients (3L: 100.0%; 4L+: 100.0%); 60.0% had prior IO use (3L: 63.4%; 4L+: 85.0%), including 53.8% IO+PBC (3L: 53.7%; 4L+: 60.0%) and 3.1% IO mono (3L: 4.9%; 4L+: 20.0%). Among 51 patients initiating AMI mono in 2L after PBC, median TTNT-D was 10.1 months. Conclusions: Among patients receiving AMI in 2L+, most initiated AMI mono after PBC, consistent with the FDA approval at the time of this study. Over half of patients had prior IO use, exposing them to suboptimal treatment and avoidable toxicity risk. Among patients receiving AMI mono in 2L following PBC, median TTNT-D was similar to median progression-free survival observed in clinical trials. 2L(n = 65) 3L(n = 41) 4L+(n = 20) Median follow-up, months 6.5 5.9 6.8 AMI mono, % 92.3 73.2 80.0 AMI combination, % 7.7 26.8 20.0 With osimertinib 4.6 19.5 15.0 Other combinations 3.1 7.3 5.0 Prior PBC use, % 83.1 100.0 100.0 Prior IO use, % 60.0 63.4 85.0 With PBC 53.8 53.7 60.0 Mono 3.1 4.9 20.0

BACKGROUND:Patients with BRCA-positive metastatic castration-resistant prostate cancer (mCRPC) have an aggressive disease course. This study aimed to describe real-world treatment patterns among patients with BRCA-positive mCRPC. MATERIALS AND METHODS:De-identified electronic health record data from the Flatiron Health-Foundation Medicine Inc. Metastatic Prostate Cancer Clinico-Genomic Database (January 01, 2011 to June 30, 2022) were used to select patients with BRCA-positive mCRPC initiating first-line (1L) therapy with an oncologist-defined advanced line of therapy (LOT) or androgen deprivation therapy (ADT) monotherapy. Treatment sequences and reasons for censoring were described in 1L, and among patients who initiated a second-line (2L) therapy. RESULTS:A total of 98 treated patients with BRCA-positive mCRPC were identified. The top 3 treatment regimens in 1L, overall, were ADT monotherapy (19%), enzalutamide (14%), and olaparib (13%). The main reason for censoring patients with ADT monotherapy was death (52.6%). Among 79 patients treated with an advanced LOT in 1L, 43.0% (n = 34) did not initiate a 2L therapy, of which, 29.4% died. In patients who initiated a 2L (n = 45), the most common 1L to 2L treatment sequence was olaparib to docetaxel (11.1%). The most prescribed 2L therapies were docetaxel (22.2%), olaparib (20.0%), abiraterone acetate (13.3%), and enzalutamide (11.1%). From 1L initiation, the median time-to-next-treatment was 6.2 months. CONCLUSION:Among patients with BRCA-positive mCRPC, ADT monotherapy, enzalutamide, and olaparib were most commonly used. Prognosis of BRCA-positive patients was poor, with most patients failing initial therapy resulting in a switch to a new therapy or death. These findings highlight the need for earlier and more effective treatments for patients with BRCA-positive mCRPC.

AIMS:To identify predictors for initiation of frontline doublet versus triplet therapy for transplant-ineligible newly diagnosed multiple myeloma. MATERIALS AND METHODS:Using Flatiron Health data, a random forest model was used to identify baseline predictors of frontline doublet or triplet use. RESULTS:The random forest model had good predictive power, with 74% probability of successfully predicting the regimen received (doublets or triplets) for a given patient. Regression analyses found that patients treated with doublets were more likely to be older (age ≥80 versus <60 years: odds ratio [OR] = 0.15, P < 0.001) and frail (frail versus fit: OR = 0.73, P = 0.023). Predictors of triplet regimen use included Black race (Black versus white: OR = 1.31, P = 0.025), urban state (urban versus rural: OR = 1.38, P = 0.042), ≥1 form of trisomy (OR = 1.39, P < 0.001), del(17/17p) (OR = 1.87, P < 0.001), detectable M protein (OR = 1.33, P < 0.001), higher disease stage per International Staging System (stage 2 versus 1: OR = 1.42, P = 0.001; stage 3 versus 1: OR = 1.35, P = 0.005), and ≥1 diagnosis for musculoskeletal and connective tissue diseases (OR = 1.45, P = 0.002). Triplet regimen use increased in recent years. CONCLUSIONS:While frontline triplet therapies have shown improved efficacy over doublets with tolerable safety, doublet use remains in older and frail patients, creating an opportunity to improve outcomes in this particular patient population.