BackgroundDry eye disease (DED) is a disorder characterized by loss of tear film homeostasis that causes ocular surface inflammation and damage. The incidence of DED increases with age. Cyclosporine ophthalmic solution 0.09% (CEQUA®; OTX-101), cyclosporine ophthalmic emulsion 0.05% (Restasis®; CsA), and lifitegrast ophthalmic solution 5% (Xiidra®; LFT) are anti-inflammatory agents indicated for DED. This analysis compared treatment patterns in patients with DED receiving OTX-101, CsA, or LFT.MethodsThis real-world, retrospective, longitudinal cohort study utilized Symphony Health Integrated Dataverse claims from July 2019 to June 2021. The dataset included all patients with OTX-101 claims and patients with CsA or LFT claims randomly selected 2:1 to OTX-101. Patients were sorted into 3 cohorts based on index treatment. Index date was that of first treatment claim, and follow-up period was from index date to end of clinical activity or data availability. Time to treatment discontinuation (TTD), probability of discontinuation, and treatment persistence were assessed for OTX-101 vs. CsA, then OTX-101 vs. LFT. Subgroup analysis was performed based on age and prior DED treatment. Kaplan-Meier analysis and log-rank test were used to examine TTD. A logistic model evaluated association between index treatment and discontinuation. Unadjusted and adjusted odds ratios, 95% confidence intervals, and P-values were reported, with statistically significant associations based on P-values < 0.05.ResultsOverall, 7102 patients (OTX-101 n = 1846; CsA n = 2248; LFT n = 3008) were eligible. Median TTD was 354 days for patients receiving OTX-101 vs. 241 days for CsA and 269 days for LFT. Log-rank test indicated TTD was significantly longer for patients on OTX-101 vs. CsA (P = 0.033). Patients on CsA were 35% more likely to discontinue treatment than patients on OTX-101; OTX-101 and LFT groups had similar discontinuation rates. After 360 days, 49.8% of patients receiving OTX-101 remained on treatment vs. 39.4% of patients on CsA (P = 0.036) and 44.0% of patients on LFT (P = 0.854).ConclusionsPatients receiving OTX-101 remained on treatment significantly longer and were significantly less likely to discontinue treatment than patients on CsA. Older patients remained on OTX-101 significantly longer than CsA. These findings highlight treatment pattern differences in patients with DED receiving these anti-inflammatory agents.

Clascoterone cream 1% is approved for the treatment of acne vulgaris in patients aged ≥12 years. Efficacy data from an open-label extension study are presented.

Tildrakizumab is an anti–interleukin-23 p19 monoclonal antibody approved for the treatment of moderate-to-severe plaque psoriasis. This analysis assesses effectiveness and safety of tildrakizumab from a real-world study of patients with moderate-to-severe plaque psoriasis.

Dry eye disease (DED) causes chronic ocular surface inflammation and damage. DED prevalence increases with age. Cyclosporine ophthalmic solution 0.09% (CEQUA®; OTX-101), cyclosporine ophthalmic emulsion 0.05% (Restasis®; CsA), and lifitegrast ophthalmic solution 5% (Xiidra®; LFT) are anti-inflammatory agents indicated for DED treatment. We compared treatment patterns in patients >64 years with DED receiving OTX-101, CsA, or LFT.

Sonidegib is approved to treat locally advanced basal cell carcinoma (laBCC) in patients not amenable to surgery or radiation. The BOLT trial demonstrated durable efficacy of sonidegib in laBCC patients over 42 months. BCC is most common in the elderly, who often take chronic medications. We evaluated the efficacy of sonidegib (200mg daily) in laBCC patients on select concomitant medications. In the Phase II BOLT study, laBCC patients were randomized 1:2 to sonidegib 200mg:800mg daily. The primary endpoint was objective response rate (ORR) per central review. Post hoc assessments included ORR and duration of response (DOR) per investigator review for patients on concomitant medications. At 42 months, ORR for laBCC patients taking sonidegib 200mg daily (n=66) was 71.2% and DOR was 15.7 months according to investigator review. Patients on select concomitant medications (n=37) had an ORR of 73.0%; DOR was not estimable. Administration of sonidegib with concomitant medications, excluding strong cytochrome P450 3A4/5 inhibitors/inducers, does not appear to alter its efficacy in laBCC patients.

BackgroundMM-II, a novel suspension of empty large multilamellar liposomes composed of dimyristoylphosphatidylcholine (DMPC) and dipalmitoylphosphatidylcholine (DPPC), has demonstrated beneficial effects in OA animal models. In a prior first-in-man study, MM-II demonstrated the ability to lower pain in knee OA patients for up to 3 months.ObjectivesThe aims of this phase 2b study were to determine an effective dose, the durability of response, and the safety of MM-II in patients with symptomatic knee OA.MethodsConsented participants were enrolled in a 6-arm randomized, double-blind, placebo-controlled 26-week trial evaluating a single IA injection of MM-II at doses of 1ml, 3ml and 6ml (150mM concentration of lipids) and placebo of matching volumes. Key inclusion criteria: age ≥ 40 years, KL grades 2 or 3, ACR OA criteria, WOMAC A pain ≥2 (0-4 Likert scale), VAS ≥50 and ≤90 (100mm scale), and intolerance/inadequate response to NSAIDs or acetaminophen. Primary endpoint was change in WOMAC A pain score at week (Wk) 12; secondary endpoints included weekly average daily pain score (ADP, e-diary) at Wks 12 & 26, WOMAC A pain at 26 wks, Patient Global Assessment (PGA) and WOMAC B and C at Wks 12 & 26, and use of rescue medication. Randomization was stratified by BMI (< 30, 30 ≤BMI<35, and BMI ≥ 35) and baseline knee pain (VAS≤74, VAS≥ 75). Statistical analysis for the primary endpoint was analyzed based on FAS using a mixed model repeated measures (MMRM) with fixed effects for treatment group, visit (Wk 1-12), and treatment-by-visit interaction and covariates of site, baseline WOMAC pain, BMI and VAS groups. Subjects were included as random effects. Treatment differences were estimated using least square means (LSM) with 95% CIs. Step-down Dunnett’s hierarchical testing procedure compared the active doses to 3 mL placebo to adjust for multiplicity. Confidence intervals were unadjusted.Results397 participants were randomized with no significant differences in baseline demographics or clinical characteristics across all treatment groups. Mean age was 62.7 (SD 8.1) years; participants were predominantly female (65.0%) and white (67.0%) with mean BMI 30.8 (SD 6.1) kg/m2. Overall, 6.8% of participants discontinued the study. The primary endpoint of WOMAC A change from baseline to Wk 12 showed LSM difference of -0.24, 95% confidence interval (CI) -0.476, -0.004, p = 0.085 for the 3ml group and -0.02, 95% CI -0.269, 0.222, p = 0.85 for the 6ml group, both vs 3ml placebo, adjusted for multiplicity. The results of the 3ml group were sustained to Wk 26. Nominal significance was seen at some time points. When comparing 3ml MM-II to the pooled placebo groups, the LSM difference in change from baseline of the WOMAC A at Wk 12 was -0.28, 95% confidence interval (CI) -0.484, -0.068, p = 0.018 adjusted for multiplicity. The LSM differences in weekly ADP scores were nominally significant at Wks 12 and 26 for the MM-II 3ml group vs 3 ml placebo: -10.9, 95% CI (-18.88, -2.83), p = 0.008 and -11.8, 95% CI (-20.19, -3.34), p =0.006, though the 6ml group was not significant (Figure 1). The changes in use of rescue medication corresponded to changes in symptoms during the trial. Treatment was well tolerated with TEAEs reported in 2.6% of MM-II and 2.9% of control participants. Injection site reactions were similar in the treatment and control groups, 1.9% and 2.9%, respectively.Figure 1.ConclusionDifferences between MM-II and placebo in WOMAC A were not statistically significant at Wk 12, though WOMAC reductions were nominally significant at some time points, and when comparing 3ml MM-II to the pooled placebo groups, results were nominally significant at Wk 12. MM-II at 3ml dose demonstrated consistent and durable reduction in weekly knee ADP scores, nominally significant compared to placebo, as early as Wk 6, with efficacy maintained through Wk 26. Treatment with MM-II was well tolerated with low levels of adverse events. MMI-II may have the ability to provide durable and relevant pain relief, warranting confirmation in further clinical studies.REFERENCES:NIL.Acknowledgements:NIL.Disclosure of InterestsPhilip G Conaghan Speakers bureau: AbbVie, Novartis, Consultant of: AbbVie, AstraZeneca, Biosplice, BMS, Eli Lilly, Galapagos, Genascence, GSK, Janssen, Merck, Moebius Medical, Novartis, Pfizer, Regeneron, Stryker, and UCB, Helene Rovsing: None declared, Edith Lau: None declared, Sidsel Lyngaard Boll: None declared, Ballari Brahmachari Employee of: Sun Pharmaceutical Industries, Inc., Richard C Chou Employee of: Sun Pharmaceutical Industries, Inc., Tarini Joshi Employee of: Sun Pharmaceutical Industries, Inc., Roni Wechsler Employee of: Moebius Medical Ltd., Siu Long Yao Employee of: Sun Pharmaceutical Industries, Inc., Sveta Weiner Employee of: Sun Pharmaceutical Industries, Inc., Asger Reinstrup Bihlet Shareholder of: NBCD A/S, Employee of: NBCD A/S, Thomas Schnitzer Consultant of: AstraZeneca, Biosplice, BMS, Galapagos, Genascence, GSK, IBSA, Lilly, Merck, Moebius Medical, Paradigm, Pfizer, Regeneron, Techfields, Xalud, Grant/research support from: None personally; to my institution: Anika, KolonTissueGene, Lilly, Paradigm, Pfizer, Regeneron, Techfields, TLC.