Matching-adjusted indirect comparison of phase 3 clinical trial outcomes of OC-01 (varenicline solution) nasal spray and lifitegrast 5% ophthalmic solution for the treatment of dry eye disease.

BACKGROUND: Matching-adjusted indirect comparison (MAIC) is a methodology for cross-study comparisons after adjusting for baseline characteristic imbalances. It is a comparative analytical approach used across therapeutic areas absent head-to-head trial outcomes. OBJECTIVE: To compare the efficacy of OC-01 (varenicline solution) 0.03 mg nasal spray (OC-01 VNS) to lifitegrast 5% ophthalmic solution on tear production and patient-reported eye dryness in patients with dry eye disease (DED) using data from phase 3 clinical trials via MAIC analysis. METHODS: Individual patient data (IPD) from the phase 3 registrational trial of OC-01 VNS and aggregate data from 2 phase 3 trials of lifitegrast in the publicly available XIIDRA New Drug Application were used. Using unanchored MAIC methods, IPD were weighted on clinically relevant baseline variables (age, race, sex, baseline Schirmer's test score [STS], and Eye Dryness Score [EDS]) to produce weighted OC-01 VNS datasets matched to the same lifitegrast datasets' variables. Least-squares (LS) mean change from baseline (CFB) in STS for OC-01 VNS was calculated using the identical analysis of covariance model and covariates used to calculate the same values for lifitegrast in the XIIDRA New Drug Application and was then compared. LS mean EDS (based on a 100- point Visual Analogue Scale) was compared via analysis of covariance in the weighted OC-01 VNS and lifitegrast datasets. OC-01 VNS at 2 and 4 weeks compared to lifitegrast data at 2 and 6 weeks. RESULTS: Data from 511 subjects (n = 260 treated; 251 vehicle control [VC]) in the OC-01 VNS phase 3 trial, 588 (n = 293 treated, 295 VC) in the lifitegrast phase 3 OPUS-1 trial, and 718 (n = 358 treated, 360 VC) in the lifitegrast phase 3 OPUS-2 trial were analyzed. The LS mean STS CFB for OC-01 VNS at 2 and 4 weeks was significantly greater than that for lifitegrast at 2 and 6 weeks in OPUS-1 and OPUS-2 (P < 0.0001 for all comparisons). The LS mean EDS CFB for OC-01 VNS at 2 and 4 weeks was significantly greater than that for lifitegrast at 2 and 6 weeks in OPUS-1 (P < 0.0001 for both comparisons) and at 4 weeks vs lifitegrast at 6 weeks in OPUS-2 (P < 0.0001). CONCLUSIONS: This MAIC analysis demonstrates OC-01 VNS produced significantly greater improvement in mean STS and comparable or greater improvement in EDS compared with lifitegrast in phase 3 trials. These findings suggest a potentially greater magnitude of improvement achieved with OC-01 VNS compared with lifitegrast for the treatment of DED within the conditions of the analysis methodology. DISCLOSURES D White is a consultant for Oyster Point Pharma, Inc. L Hendrix, M Macsai, and A Gibson are employees and shareholders for Oyster Point Pharma, Inc. L Sun was an employee of COEUS, Clinical Research at the time of study conduct and received funding from Oyster Point Pharma, Inc. I Tam is an employee of COEUS, Clinical Research and received funding from Oyster Point Pharma, Inc. Oyster Point Pharma, Inc was involved in the study design, data collection, data analysis, and preparation of the manuscript and is the manufacturer/licensee of OC-01 (varenicline solution) nasal spray. Oyster Point Pharma, Inc., sponsored the phase 3 OC-01 (varenicline solution) clinical study from which analysis data were obtained.

Medical and mental health implications of gestational surrogacy.

Gestational surrogacy in the United States has quadrupled since 1999, but to date, only a few states explicitly permit compensated gestational surrogacy. Current legal prohibitions are often influenced by outdated and stereotyped understandings of surrogacy. It is increasingly important to understand the current literature about the medical and mental health impacts of surrogacy and how state legislatures have addressed compensated gestational surrogacy in recent years. Based on this review, we found no evidence of substantial adverse medical or psychological outcomes among women who are gestational carriers or among the children they give birth to. The literature suggests that gestational surrogacy is a safe and increasingly popular option for families as long as rigorous screening and medical, psychological, and social supports are equitably provided. As states move to responsibly legalize and regulate gestational surrogacy, there is a continued need for further longitudinal studies on the health and psychological outcomes of gestational surrogacy.

Physician Satisfaction with Anti-Inflammatory Topical Medications for the Treatment of Dry Eye Disease.

PURPOSE: Dry eye disease (DED) is one of the most common ophthalmic disorders. Pathogenesis of the disease includes inflammation of the ocular surface and lacrimal gland. Two anti-inflammatory prescription treatments are currently available: cyclosporine ophthalmic emulsion 0.05% (CYC) and lifitegrast 5% ophthalmic solution (LIF). The objective of this survey-based study was to assess physician satisfaction with CYC and LIF for the treatment of DED. METHODS: Physicians currently treating DED patients with CYC or LIF were asked to rate the experiences of their patients currently or formerly using CYC and LIF, and their own perspectives on the two treatments. RESULTS: Twenty-one physicians participated in the survey, providing responses on behalf of 210 patients. Overall, physicians reported low levels of satisfaction with onset of action of CYC and LIF, and fewer than half considered either drug to be effective in managing symptoms or improving patient quality of life (QoL). Burning sensation and dysgeusia were the most frequently reported side effects. Onset of action and effectiveness after onset were the main switching drivers. Although two-thirds of physicians were satisfied with the overall effectiveness of CYC and LIF, all physicians agreed that more DED treatment options are needed, with >50% strongly agreeing. CONCLUSION: Physicians perceived a gap in DED management with currently available topical anti-inflammatory agents. Although satisfaction with CYC and LIF was high, few physicians considered these medications to be effective in managing symptoms or improving QoL.

Treatment Satisfaction Among Patients Using Anti-Inflammatory Topical Medications for Dry Eye Disease.

PURPOSE: To assess patient satisfaction among current and former users of the anti-inflammatory topical medications, cyclosporine A 0.05% (CYC) and lifitegrast 5.0% (LIF), for the management of dry eye disease (DED). PATIENTS AND METHODS: Patients with DED were recruited via physician referral to participate in a survey. Current users of CYC or LIF were asked to rate their experience in terms of satisfaction, side effects, and limitation of activities. Switchers of CYC to LIF or LIF to CYC were asked to rate the importance of potential reasons for switching. RESULTS: Surveys were completed by 207 patients currently treated with CYC (n=98), LIF (n=96), or other DED medications (n=13). Although overall satisfaction with current treatment was high, current users of CYC and LIF reported ineffective relief of DED symptoms (31% and 22%, respectively) and dissatisfaction with the time to onset of effect (29% and 11%). Substantial proportions of patients reported 'sometimes', "usually", or 'always' experiencing the following side effects: burning sensation (72% CYC, 64% LIF), itching (43% CYC, 44% LIF), altered sensation of taste (21% CYC, 56% LIF), blurred vision (37% CYC, 50% LIF), and discharge (28% CYC, 30% LIF). Of the 30 switchers of CYC to LIF and 31 switchers of LIF to CYC, the majority reported inability to relieve DED symptoms as a very or extremely important switching reason. Despite switching, one in four patients were somewhat dissatisfied or dissatisfied with their current medication, with 37% of patients reporting ineffective symptom relief. CONCLUSION: Although the rate of overall satisfaction was generally high with both LIF and CYC, many patients were unable to achieve effective symptom relief and commonly experienced side effects. The proportion of patients who were dissatisfied and/or unable to achieve effective symptom relief even after switching suggests the need for additional treatment options for managing DED.

Chronic Conjunctivitis From a Retained Contact Lens.

PURPOSE: To help clinicians diagnose and manage unilateral recalcitrant chronic bacterial conjunctivitis secondary to a retained soft contact lens and describe the first report of Gram-negative bacteria causing this condition. METHODS: Chart review of successive cases presenting with unilateral chronic conjunctivitis with positive cultures and a retained contact lens. RESULTS: Three cases were identified and described. Culturing of the retained contact lenses grew Pseudomonas aeruginosa in the first case, Achromobacter xylosoxidans in the second, and Staphylococcus epidermidis in the third. All three patients were successfully treated with removal of the retained lens and targeted antibiotic eyedrop therapy. CONCLUSIONS: Unilateral chronic recurrent or recalcitrant purulent papillary conjunctivitis is rare, and a retained contact lens should be suspected in patients with a history of wearing contact lenses. Careful examination with double eversion of the upper eyelid and sweeping of the fornices can recover the offending lens. Although only Gram-positive organisms have been isolated in previous reports, two of our three cultures grew Gram-negative organisms, highlighting the importance of broad-spectrum antibiotic usage for these cases.

Real-World Treatment Patterns Of Cyclosporine Ophthalmic Emulsion And Lifitegrast Ophthalmic Solution Among Patients With Dry Eye.

PURPOSE: To assess adherence, non-persistence, discontinuation, and switching of topical cyclosporine ophthalmic emulsion 0.05% (CYC) and lifitegrast ophthalmic solution 5% (LIF) use in the real world among patients with dry eye disease (DED). DESIGN: Retrospective insurance claims study. METHODS: Adult patients with DED and ≥1 prescription claim for CYC or LIF (first claim = index date) in the IBM® MarketScan® databases from July 2016 to February 2018 were identified. Eligible patients had continuous medical and pharmacy benefits in the 12 months pre- and post-index periods, and no prior use of the index medication. The proportion of days covered (PDC), adherence, non-persistence, discontinuation, and switching were examined over the 12-month post-index period. RESULTS: This study included 6537 CYC and 3235 LIF patients. The adherence rate was 5.9% for CYC and 9.7% for LIF; the median PDC was 0.3 for both cohorts. Overall, 70.8% of CYC and 64.4% of LIF patients discontinued treatment with median days to discontinuation of 89 and 29, respectively. Non-persistence was 7.1% for CYC and 6.8% for LIF (median days to discontinuation: 89 and 105). In addition, 5.0% switched from CYC to LIF, and 9.6% switched from LIF to CYC over the post-index period. CONCLUSION: Over 60% of DED patients discontinued treatment within 12 months of initiation; the median time to discontinuation was 3 months for CYC and 1 month for LIF. Although this analysis did not capture the reasons why patients discontinued treatment, the results demonstrate there likely exists a significant unmet need amongst DED patients.

Safety and efficacy of amniotic cytokine extract in the treatment of dry eye disease.

Purpose: Evaluate the safety and efficacy of cryopreserved amniotic cytokine extract (ACE) in the treatment of subjects with dry eye disease (DED). Patients and methods: This was a retrospective, multicenter, chart review of adult patients with DED that instilled cryopreserved ACE drops twice-daily for 4 or 12 weeks. Patients had corneal fluorescein staining (0-20 range) and/or a lissamine green conjunctival staining score (0-18 range) of ≥3 and ≤9 in at least 1 eye and a score ≥40 (0-100 range) of eye dryness/irritation on a visual analog scale (VAS). Following completion of a treatment course, medical records were reviewed from the initiation of therapy (baseline), and at post-treatment visits (4 weeks, 8 weeks, and 12 weeks). Patient records for visual acuity, adverse events, corneal fluorescein staining, conjunctival lissamine green staining, and symptom scores of ocular dryness/irritation were reviewed for each visit, as available. Safety and tolerability were assessed through the evaluation of patient-reported adverse events recorded in the medical records. Results: A total of 54 eligible patients were identified at 7 clinical sites; 16 patients administered ACE drops for 4-weeks, and 38 patients instilled ACE drops for 12 weeks. Significant improvements in the mean changes from baseline were observed for corneal fluorescein staining, lissamine green staining, visual acuity (LogMar) and VAS ocular symptom scores at the 4-week post-treatment visit (p<0.01). Additional improvements continued out to the 12-week follow-up assessment visits. Two patients discontinued therapy due to reports of ocular burning or foreign body sensation. Conclusion: The cryopreserved ACE formulation was well-tolerated and effective in reducing the clinical signs and symptoms of DED. Conduct of a vehicle-controlled prospective study is warranted.

The influence of plaintiff's body weight on judgments of responsibility: the role of weight bias.

PROBLEM: The current study investigated the influence of a plaintiff's weight and the location of an accident on a simulated jury's perceptions of plaintiff's personal responsibility for an accident. METHODS: Participants were 185 lean and overweight male and female adults (mean self-reported body mass index: 24.87±5.45) who read one of three vignettes describing an accident that occurred while leaving one of three different establishments (fast food burger restaurant; fitness gym; department store) while viewing one of two silhouettes of the alleged plaintiff (a lean female; an obese female). RESULTS: Participants were significantly more likely to report the plaintiff's weight entered into their perceptions of personal responsibility when they viewed the overweight plaintiff compared to the thin plaintiff. As respondent's self-reported weight bias increased, participants were more likely to hold the plaintiff responsible and more likely to blame plaintiff characteristics for the accident. CONCLUSION: The weight of a plaintiff may affect juror perceptions of personal responsibility particularly if the juror possesses self-reported weight bias.