Consecutive Monthly Doses Research Articles

Safety and efficacy profile of intravitreal ranibizumab vs dexamethasone in treatment of naïve diabetic macular edema.

To compare the safety and efficacy parameters of intravitreal ranibizumab vs intravitreal dexamethasone (IVD) in the treatment of patients with naïve diabetic macular edema (DME) in terms of best-corrected visual acuity (BCVA), central macular thickness (CMT), and possible complications like intraocular pressure (IOP) rise and cataract progression. A hospital-based prospective and comparative study of naïve DME patients was conducted between November 2020 and October 2021 with a minimum follow-up (F/U) period of 6 months. Thirty phakic patients received one dose of IVD implant (Group A) and the other 30 (Group B) received three consecutive monthly doses of ranibizumab. The main exclusion criteria were steroid responders and the presence of ocular inflammation. The mean pre-injection CMT in Group A was 405µ and reduced to 297.07µ at 3 months and 278.35µ at 6 months. Mean increase in logMAR BCVA was 0.55. The mean pre-injection IOP was 16.28 and 17.64 mm of Hg at 6 months. In Group B, the mean pre-injection CMT was 401.07µ and reduced to 276.1µ at 3 months and 292.9µ at 6 months. Mean BCVA increased to 0.37. The mean pre-injection IOP was 17.28 mm Hg and 16.42 mm Hg at 6 months. There was no significant progression of cataract in both groups. The mean decrease in CMT was comparable in both the groups at 6 months F/U with an improvement of BCVA with no significant IOP fluctuation or cataract progression. Hence, IVD appears to be noninferior to ranibizumab in the treatment of naïve DME.

Effects of Fremanezumab on Psychiatric Comorbidities in Difficult-to-Treat Patients with Chronic Migraine: Post Hoc Analysis of a Prospective, Multicenter, Real-World Greek Registry.

this post hoc analysis aimed to evaluate the efficacy of fremanezumab in difficult-to-treat chronic migraine (CM) patients with and without psychiatric comorbidities (PCs), mainly anxiety and/or depression. We assessed data from CM patients with and without PCs who failed at least 3 preventives and eventually received at least 3 consecutive monthly doses of fremanezumab 225 mg. Outcomes included the crude response (≥50% reduction in monthly headache days (MHDs)) rates to fremanezumab from the baseline to the last clinical follow-up. The changes in MHDs; MHDs of moderate/greater severity; monthly days with intake of abortive medication; and the proportion of patients' changing status from with PCs to decreased/without PCs were also compared. Disability and quality of life (QOL) outcomes were also assessed. Of 107 patients enrolled, 65 (60.7%) had baseline PCs. The percentage of patients with (n = 38/65; 58.5%) and without (n = 28/42; 66.6%) PCs that achieved a ≥50% reduction in MHDs with fremanezumab was comparable (p = 0.41), whereas MHDs were significantly reduced (difference vs. baseline) in both patients with PCs (mean -8.9 (standard error: 6.8); p < 0.001) and without PCs (-9.8 (7.5); p < 0.001). Both groups experienced significant improvements in all other efficacy, disability, and QOL outcomes at comparable rates, including in MHD reduction. A significant proportion of fremanezumab-treated patients with baseline PCs de-escalated in corresponding severities or even reverted to no PCs (28/65; 43.1%) post-fremanezumab. fremanezumab appears to be effective as a preventive treatment in difficult-to-treat CM patients with and without PCs while also being beneficial in reducing the severity of comorbid anxiety and/or depression.

Effectiveness of the Use of Three-Dose Intravitreal Ziv-Aflibercept in the Management of Diabetic Macular Edema in a Real-Life Setting.

It has been reported that intravitreal Ziv-aflibercept is a safe and effective drug for the treatment of diabetes macular edema (DME). The objective of this study was to evaluate in a real-life setting, the efficacy of intravitreal Ziv-aflibercept in the treatment of DME after the administration of three consecutive monthly doses. A single arm, prospective cohort study. We included patients with DME who received three doses of intravitreal Ziv-aflibercept. Data such as best corrected visual acuity (BCVA) and tomographic biomarkers before treatment and a month after the third dose were collected. DME was staged using the Panozzo classification. Thirty-eight patients participated for a total of 53 eyes. The mean age was 59 ± 8.1 years. We observed significant changes after the third dose in the parameters studied (BCVA in LogMAR pre-treatment (0.6 ± 0.33) and post-treatment (0.4 ± 0.29) [p<0.001], macular thickness pre-treatment (501 ± 167 µm) and post-treatment (324 ± 114 µm) [p<0.001], macular volume pre-treatment 10.8 (7.5-17.8) mm3 and post-treatment 9.3 (0-13.6) mm3 [p<0.005]). And 73.6% of the patients presented an advanced severe stage during their pre-treatment evaluation and after post-treatment, 64.2% of the patients no longer presented edema. No systemic or ocular adverse events occurred. The use of three consecutive monthly doses of intravitreal Ziv-aflibercept in a real-life setting is effective and safe in the management of diabetic macular edema.

Laboratory safety evaluation of lokivetmab, a canine anti-interleukin-31 monoclonal antibody, in dogs

Lokivetmab (Cytopoint®, Zoetis) is a canine monoclonal antibody that specifically binds and neutralizes interleukin (IL)-31. Lokivetmab is approved for use in dogs for the treatment of atopic dermatitis (AD) and allergic dermatitis. The laboratory safety of lokivetmab was evaluated in 2 studies by adapting the science-based, case-by-case approach used for preclinical and early clinical safety evaluation of human biopharmaceuticals. The main objectives were to demonstrate the safety of lokivetmab in healthy laboratory Beagle dogs by using integrated clinical, morphologic, and functional evaluations. In Study 1, dogs were treated s.c. with saline or lokivetmab at 3.3 mg/kg (1X, label dose) or 10 mg/kg (3X intended dose) for 7 consecutive monthly doses, with terminal pathology and histology assessments. In Study 2, the functional immune response was demonstrated in naïve dogs using the T-cell dependent antibody response (TDAR) test with 2 different dose levels of unadjuvanted keyhole limpet hemocyanin (KLH) as the model immunogen. The primary endpoint was anti-KLH IgG antibody titer, and secondary endpoints were ex vivo IL-2 enzyme-linked immunospot (ELISpot) and peripheral blood mononuclear cell lymphoproliferation assays. Both studies included monitoring general health, periodic veterinary clinical evaluations, serial clinical pathology and toxicokinetics, and monitoring for anti-drug antibodies.In both studies, the health of dogs receiving lokivetmab was similar to controls, with no treatment-related changes uncovered. Extensive pathology evaluations of immune tissues (Study 1) revealed no lokivetmab-related morphologic changes, and in dogs treated at 10 mg/kg lokivetmab, immunization with the model antigen KLH did not impair the functional antibody or T-cell recall responses. There were no immunogenicity-related or hypersensitivity-related responses observed in either study. These studies in healthy laboratory dogs showed that lokivetmab was well-tolerated, did not produce any treatment-related effects, and had no effect on immune system morphology or its functional response. These studies also demonstrated the utility of a science-based case-by-case approach to the safety evaluation of a veterinary biopharmaceutical product.

Preventive efficacy of six monthly oral doses of Simparica Trio\xae, Heartgard\xae Plus, and Interceptor\xae Plus against a macrocyclic lactone-resistant strain (ZoeLA) of heartworm (Dirofilaria immitis) in dogs

BackgroundAdministration of four to six consecutive monthly doses of 24 µg/kg moxidectin alone shows high effectiveness in preventing the maturation of macrocyclic lactone (ML)-resistant heartworm strains, Dirofilaria immitis JYD-34 and ZoeLA. This laboratory study evaluated the efficacy of six consecutive monthly oral doses of Simparica Trio® (moxidectin/sarolaner/pyrantel) compared to six monthly doses of either Heartgard® Plus (ivermectin/pyrantel) or Interceptor® Plus (milbemycin oxime/praziquantel) against ML-resistant D. immitis ZoeLA strain.MethodsBeagle dogs were inoculated with 50 third-stage (L3) D. immitis larvae (ZoeLA) 30 days prior to the first treatment. Dogs were randomized to treatment (six animals in each group) with six monthly oral doses of placebo, Simparica Trio, Heartgard Plus, or Interceptor Plus at their respective label doses. Microfilaria (MF) and antigen tests were conducted periodically, and efficacy was evaluated by necropsy for adult heartworms approximately 9 months after L3 inoculation.ResultsAdult heartworms were recovered from all six placebo dogs, with a geometric mean of 35.5 worms (range, 23–48). Five of the six dogs treated with Simparica Trio were infected with a geometric mean of 1.0 worms (range, 0–3), and all remained MF-negative. All Heartgard Plus-treated dogs (six) were infected with a geometric mean of 32.5 worms (range, 22–38); five of these dogs were MF-positive at day 236. All Interceptor Plus-treated dogs (six) were infected with a geometric mean of 22.8 worms (range, 10–34); five of these dogs were MF-positive at day 236. The efficacy of six consecutive doses with Simparica Trio, Heartgard Plus, and Interceptor Plus against ZoeLA was 97.2, 8.5, and 35.9%, respectively. Adult worm counts for the Simparica Trio-treated group were significantly lower (P < 0.0001) than placebo control, Heartgard Plus, and Interceptor Plus-treated groups. Adult worm counts for Heartgard Plus and Interceptor Plus were not significantly different from placebo (P > 0.05).ConclusionsSimparica Trio prevented microfilaremia in all dogs and was highly effective (97.2%) and significantly better than either Heartgard Plus (8.5%) or Interceptor Plus (35.9%) in preventing the development of the ZoeLA ML-resistant heartworm strain when administered for six consecutive months in this comparative laboratory efficacy study.Graphical

Treat-and-Extend Regimens for the Management of Neovascular Age-related Macular Degeneration and Polypoidal Choroidal Vasculopathy: Consensus and Recommendations From the Asia-Pacific Vitreo-retina Society.

Purpose:Review and provide consensus recommendations on use of treat-and-extend (T&E) regimens for neovascular age-related macular degeneration (nAMD) and polypoidal choroidal vasculopathy (PCV) management with relevance for clinicians in the Asia-Pacific region.Methods:A systematic search of MEDLINE, EMBASE, and Cochrane databases, and abstract databases of the Asia-Pacific Vitreo-retina Society, European Society of Retina Specialists, American Academy of Ophthalmology, and Controversies in Ophthalmology: Asia-Australia congresses, was conducted to assess evidence for T&E regimens in nAMD. Only studies with ≥100 study eyes were included. An expert panel reviewed the results and key factors potentially influencing the use of T&E regimens in nAMD and PCV, and subsequently formed consensus recommendations for their application in the Asia-Pacific region.Results:Twenty-seven studies were included. Studies demonstrated that T&E regimens with aflibercept, ranibizumab, or bevacizumab in nAMD, and with aflibercept in PCV, were efficacious and safe. The recommendation for T&E is, after ≥3 consecutive monthly loading doses, treatment intervals can be extended by 2 to 4 weeks up to 12 to 16 weeks. When disease activity recurs, the recommendation is to reinject and shorten intervals by 2 to 4 weeks until fluid resolution, after which treatment intervals can again be extended. Intraretinal fluid should be treated until resolved; however, persistent minimal subretinal fluid after consecutive treatments may be tolerated with treatment intervals maintained or extended if the clinical condition is stable.Conclusions:T&E regimens are efficacious and safe for nAMD and PCV, can reduce the number of visits, and minimize the overall burden for clinicians and patients.

Comparative preventive efficacy of ProHeart\xae 12, Heartgard\xae Plus and Interceptor\xae Plus against a macrocyclic lactone-resistant strain (JYD-34) of heartworm (Dirofilaria immitis) in dogs

BackgroundThe current studies compared ProHeart® 12, Heartgard® Plus and Interceptor® Plus for preventive efficacy against JYD-34, a macrocyclic lactone (ML)-resistant strain of Dirofilaria immitis in dogs.MethodsIn two studies, each using 24 adult beagles, dogs were allocated to four treatment groups (n = 6): placebo-treated control; ProHeart 12 as per label (0.5 mg/kg moxidectin); Heartgard Plus (HGP) as per label (minimum 6 µg/kg ivermectin); and Interceptor Plus (INP) as per label (minimum 0.5 mg/kg milbemycin oxime). In both studies, ProHeart 12 was administered as a single subcutaneous dose on day 0, and HGP and INP were administered orally on days 0, 30, 60, 90, 120 and 150. In Studies 1 and 2, dogs were inoculated with 50 third-stage heartworm larvae (JYD-34 strain) on days −30 and 165, respectively. In Study 2, treatment for both HGP and INP was continued on days 180, 210, 240, 270, 300 and 330. Adult heartworm recoveries were performed on day 185 in Study 1 and on day 360 in Study 2.ResultsIn Studies 1 and 2, all placebo-treated dogs developed adult heartworm infections (geometric mean, 29.9 and 34.9 worms/dog, respectively). A single dose of ProHeart 12 was 100% effective in preventing the development of adult JYD-34 heartworms when treatment was initiated 30 days after heartworm inoculation, while six consecutive monthly doses of HGP and INP were only 10.5% and 14.6% effective, respectively. The mean worm count for the ProHeart 12-treated group was significantly lower (P < 0.0001) than that for the placebo control, HGP- and INP-treated groups. In Study 2, the dogs treated with ProHeart 12 had an efficacy of 98.3%. All dogs treated with HGP and INP for 12 consecutive months had adult heartworms with efficacies of 37.7% and 34.9%, respectively. The mean worm count for the ProHeart 12-treated dogs was significantly lower (P < 0.0001) than those for the control group, HGP- and INP-treated groups.ConclusionsA single administration of ProHeart 12 was 98–100% effective in preventing the development of the ML-resistant JYD-34 heartworm strain and was significantly better than multiple consecutive monthly doses of either Heartgard Plus or Interceptor Plus in both studies.Graphical

COMPARATIVE EFFICACY OF INTRAVITREAL RANIBIZUMAB MONOTHERAPY WITH COMBINED INTRAVITREAL RANIBIZUMAB AND LASER PHOTOCOAGULATION THERAPY IN THE MANAGEMENT OF DIABETIC MACULAR EDEMA.

Background: In this study, best corrected visual acuity and macular thickness were compared before and after intravitreal injection Ranibizumab monotherapy and combined therapy of injection Ranibizumab and laser, in patients with macular oedema ≥350µm measured with spectral domain OCT. Objective:Our specific objective is to identify the best treatment option in NPDR with macular thickness ≥350µm in Type 2 diabetic retinopathy patients depending upon the anatomical and functional outcome in each group. Method: Sixty (60) newly diagnosed eyes of NPDR with macular oedema (30 patients in each group) attending retina research clinic of Regional Institute of Ophthalmology,Kolkata were included in this study. Result: This parallel group comparison trial has shown that a combination of 3 consecutive monthly doses of intravitreal ranibizumab followed by modified grid laser therapy 7-10 days latter is more effective in reducing central macular thickness in comparison to only multiple injections of ranibizumab,but there is no difference in the final best corrected visual acuity attained in between the two groups. Conclusion: Laser photocoagulation along withanti-vascularendothelialgrowthfactoragentisthestrongerweapontofightagainstblindnessindiabeticmacularedema

Preventive efficacy of four or six monthly oral doses of 24 \xb5g/kg moxidectin compared to six monthly doses of Heartgard\xae Plus or Interceptor\xae Plus against macrocyclic lactone-resistant heartworm (Dirofilaria immitis) strains in dogs

BackgroundRecent reports indicated that increasing the monthly oral dosage and the number of consecutive monthly doses of moxidectin improved the efficacy against macrocyclic lactone (ML)-resistant Dirofilaria immitis. The two laboratory studies reported here evaluated the efficacy of four or six monthly oral doses of 24 µg/kg moxidectin compared to six monthly doses of either Heartgard® Plus (ivermectin/pyrantel) or Interceptor® Plus (milbemycin oxime/praziquantel) against ML-resistant D. immitis strains.MethodsDogs were inoculated 30 days prior to first treatment with 50 third-stage (L3) larvae of a ML-resistant strain of D. immitis, ZoeLA or JYD-34. In each study, dogs (six per group) were randomized to treatment with six monthly doses of placebo, four or six monthly doses of 24 µg/kg moxidectin, or six monthly doses of Heartgard® Plus or Interceptor® Plus at their label dose rates. Efficacy was evaluated by adult heartworm counts approximately nine months after L3 inoculation.ResultsAll negative-control dogs were infected with adult heartworms (geometric mean, 35.6; range, 24–41) for ZoeLA and (geometric mean, 32.9; range, 30–37) for JYD-34. Efficacies against ZoeLA for moxidectin, Heartgard® Plus and Interceptor® Plus were ≥ 96.1%, 18.7% and 21.2%, respectively. Adult counts for both moxidectin-treated groups were significantly lower than negative control (P < 0.0001), significantly lower than Heartgard® Plus and Interceptor® Plus (P < 0.0001), but not significantly different from each other (P = 0.5876). Counts for Heartgard® Plus and Interceptor® Plus were not significantly different than negative control (P ≥ 0.2471). Efficacies against JYD-34 were ≥ 95.9%, 63.9% and 54.6% for moxidectin, Heartgard® Plus and Interceptor® Plus, respectively. Counts for all groups were significantly lower than negative control (P ≤ 0.0001). Counts for six monthly doses of moxidectin were significantly lower than those for four monthly doses (P = 0.0470), and the counts for both moxidectin-treated groups were significantly lower than Heartgard® Plus and Interceptor® Plus (P ≤ 0.0002).ConclusionsMoxidectin administered orally at 24 µg/kg to dogs for four or six consecutive months was ≥ 95.9% effective in preventing the development of two ML-resistant heartworm strains and resulted in significantly fewer adult D. immitis than in dogs treated with Heartgard® Plus or Interceptor® Plus when administered for six consecutive months at their approved label dosages in two laboratory efficacy studies.

Evaluation of goserelin effectiveness based on assessment of inflammatory cytokines and symptoms in uterine leiomyoma.

Background Uterine leiomyoma is a benign tumour of the uterine smooth muscles associated with an elevated level of inflammatory cytokines. Goserelin, a synthetic gonadotropin-releasing hormoneanalogue, suppresses the production of sex hormones and release of inflammatory cytokines in uterine leiomyoma cells. Objective The primary objective of this study was to find out the effectiveness of subcutaneous goserelin therapy on lowering serum levels of inflammatory cytokines and improving uterine leiomyoma-related symptoms in female patients diagnosed with uterine leiomyoma. The secondary objective was to assess the tolerability to goserelin therapy used in the management of this tumour. Setting Outpatient gynaecological clinic of the medical consultation department of Baghdad Teaching Hospital, Baghdad province, Iraq. Methods A single centre, prospective, longitudinal, cohort study was carried out on female patients diagnosed with uterine leiomyoma. Goserelin 3.6mg subcutaneous injection was given in a consecutive monthly dose for the total time duration of three months. Serum levels of inflammatory cytokines, tumour necrosis factor-α and monocyte chemotactic protein-1 were detected before and after goserelin therapy in a consecutive monthly assessment. The study also assessed the improvement in uterine leiomyoma-related symptoms, including pelvic pain alongside the incidence of goserelin-related side effects during therapy schedules. Main Outcome Measures Assessment of serum levels of tumour necrosis factor-α and monocyte chemotactic protein-1 alongside uterine leiomyoma-related symptoms, including pelvic pain and goserelin-related side effects. Results There was a significant decrease in serum levels of tumour necrosis factor-α and monocyte chemotactic protein-1 compared to the baseline level over the 3-month duration of goserelin therapy (0.11 ± 0.02 vs. 0.74 ± 0.19) pg/mL; (0.07 ± 0.00 vs. 0.44 ± 0.18) pg/mL respectively. Patients showed a clinical improvement regarding uterine leiomyoma-related symptoms following each of the consecutive monthly doses of goserelin therapy (n = 11, 55%, P < 0.0001; n = 15, 75%, P < 0.0001; n = 18, 90%, P < 0.0001) respectively. This also includes a significant decrease in the intensity of leiomyoma-related pelvic pain before and after goserelin therapy (7.2 ± 1.43 vs. 3.05 ± 1.14, P < 0.0001). The majority of patients reported vaginal dryness (60%) as the main goserelin-related side effect. Conclusion Goserelin therapy reduces serum levels of inflammatory cytokines, tumour necrosis factor- α and monocyte chemotactic protein-1, improving leiomyoma-related symptoms with good tolerability in patients with uterine leiomyoma.

Efficacy of three consecutive monthly doses of a topical formulation of selamectin and sarolaner (Revolution® Plus/Stronghold® Plus) compared with a single dose of fluralaner (Bravecto® for Cats) against induced infestations of Ctenocephalides felis on cats

In a controlled laboratory study, the efficacy against fleas, Ctenocephalides felis, of a single treatment of fluralaner topical solution (Bravecto® for Cats, Merck) was compared with that of three consecutive monthly topical treatments with selamectin and sarolaner (Revolution® Plus, Zoetis). Twenty-four domestic short hair cats were ranked based on host suitability flea counts to form groups of three and were randomly assigned within group to one of three treatments. The first group received a topical treatment with (a) placebo (vehicle control for Revolution® Plus) on Days 0, 30, and 60, (b) 6 mg/kg selamectin and 1 mg/kg sarolaner on Days 0, 30, and 60, or (c) 40 mg/kg fluralaner on Day 0 and placebo (vehicle control for Revolution® Plus) on Days 30 and 60. Because doses were rounded off, the selamectin plus sarolaner-treated cats received effective dosages of 5.25–6.60 mg/kg selamectin and 0.88–1.10 mg/kg sarolaner, while the fluralaner-treated cats received dosages of 34.71–43.08 mg/kg fluralaner. All cats were infested with 100 (±5) fleas on Day -1 and at biweekly intervals after that, from Day 13 to Day 89. Flea comb counts were conducted 24 hours after treatment or after re-infestation.There were no adverse events related to treatment during the study. Except for a single cat from which 20 fleas were recovered on Day 90, all other placebo-treated cats had at least 48 fleas at each count, indicating adequacy of infestation of the controls. Based on geometric mean live flea counts, three consecutive monthly treatments with Revolution® Plus resulted in consistent and high efficacy of ≥98.6% compared with placebo throughout the study. A single treatment with Bravecto® for Cats provided consistent and high efficacy of ≥94.6% on all count days during a period of 12 weeks, the approved duration of efficacy for the product. Based on the efficacy results of the study, both products were equivalent in their ability to control fleas on cats. Use of Bravecto® for Cats every 12 weeks or the consecutive monthly use of Revolution® Plus is expected to provide extended high residual kill over the respective labeled durations of efficacy of the two products.

The efficacy of a novel topical formulation of selamectin plus sarolaner (Revolution® Plus/Stronghold® Plus) in preventing the development of Dirofilaria immitis in cats

Three controlled studies were conducted to investigate the efficacy of selamectin plus sarolaner (Revolution® Plus/Stronghold® Plus) in preventing feline heartworm disease in cats. In all studies, cats were inoculated with 100 Dirofilaria immitis third stage larvae on Day -30. In the first study, cats were treated with selamectin plus sarolaner as a single dose on Day 0 or as three consecutive monthly doses on Days 0, 28 and 56. In the second and third studies, cats were treated with either sarolaner alone on Day 0, selamectin plus sarolaner on Day 0 or selamectin plus sarolaner as three consecutive monthly doses on Days 0, 28 and 56. In all three studies, dosages were 6 mg/kg selamectin plus 1 mg/kg sarolaner or 1 mg/kg sarolaner alone. Control cats were given a placebo containing inert formulation ingredients (vehicle). All treatments were administered at a single site topically to the skin cranial to the scapulae. Cats were humanely euthanized on Day 145/146 (i.e., 175/176 post-inoculation), and adult D. immitis worms were recovered and enumerated. Across the three studies, adult heartworms were recovered from 87 to 100% of control cats, with geometric mean worm counts ranging from 2.1 to 5.4. No adult D. immitis worms were recovered from cats treated with selamectin plus sarolaner. Cats treated with sarolaner alone were not protected against D. immitis infection, showing geometric mean worm counts of 1.9 to 2.4. In these studies, selamectin (6 mg/kg) plus sarolaner (1 mg/kg) was 100% effective in preventing heartworm development in cats when administered topically as one dose 30 days after inoculation or as three consecutive monthly doses starting 30 days post-inoculation. These studies demonstrated that a single topical administration of selamectin plus sarolaner at the recommended dosage was completely effective in preventing the development of D. immitis in cats.

In-home assessment of either topical fluralaner or topical selamectin for flea control in naturally infested cats in West Central Florida, USA

BackgroundAn investigation was conducted in West Central Florida, USA to evaluate the efficacy of either topically applied fluralaner or topically applied selamectin to control flea infestations, minimize dermatologic lesions and reduce pruritus in naturally flea infested cats over a 12-week period. When dogs were present in the households, they were treated with either oral fluralaner (if household cats were treated with topical fluralaner) or oral sarolaner (if household cats were treated with topical selamectin).MethodsThirty-one cats in 20 homes were treated once with fluralaner topical solution on day 0 and 18 dogs in these homes were administered a single fluralaner chewable. Twenty-nine cats in 18 homes were treated once monthly with a selamectin topical solution for 3 treatments and 13 dogs in these same homes were treated once monthly for 3 treatments with a sarolaner chewable. Fleas on cats were counted by flea combing, fleas on dogs were estimated using visual area counts and fleas in the indoor premises were assessed using intermittent-light flea traps. Blinded-assessments of feline dermatologic lesions were conducted monthly and pruritus severity was evaluated by pet owners.ResultsA single topical application of fluralaner reduced flea populations on cats by 96.6% within 7 days and by 100% at 12 weeks post-treatment. This efficacy was significantly greater than selamectin treatment where single topical application reduced flea populations on cats by 79.4% within 7 days of initial treatment and 3 consecutive monthly treatments reduced flea populations by 91.3% at the end of 12 weeks. At the end of the 12-week study, all fluralaner-treated cats were flea-free and this was significantly greater than the 38.5% of selamectin treated cats that were flea-free. At the end of the study, fleas were completely eradicated (from cats, dogs and homes) in 95.0% of fluralaner treatment group homes, significantly greater than the 31.3% of selamectin/sarolaner treatment group homes with complete flea eradication. Owner reported cat pruritus was reduced similarly in both treatment groups. Significant improvements in dermatologic lesion scores were achieved by day 30 in fluralaner treated cats and by day 60 in selamectin treated cats.ConclusionsAn in-home investigation in subtropical Florida found that 1 application of topical fluralaner eliminated flea infestations on cats and in homes significantly more effectively than 3 consecutive monthly doses of selamectin.

Evaluation of contrast sensitivity and other visual function outcomes in diabetic macular edema patients following treatment switch to aflibercept from ranibizumab.

PurposeThis study aims to investigate changes in contrast sensitivity (CS), visual acuity (VA), central retinal thickness (CRT), and vision-related quality of life in subjects with recalcitrant diabetic macular edema switched from long-term ranibizumab treatment to aflibercept.Patients and methodsIn this prospective, investigator-masked, single-center study, 40 patients with persistent fluid, despite previous ranibizumab treatment, were switched to aflibercept with 5 consecutive monthly doses. The primary outcome was mean change from baseline to week 20 in Pelli–Robson CS. Secondary outcomes were mean change from baseline in best-corrected VA (BCVA), CRT, and National Eye Institute 25-Item Visual Function Questionnaire score.ResultsFifty eyes (baseline VA >6/30) were evaluated. A median of 21.1±11.9 (range 5–55) ranibizumab injections were administered prior to initiation of aflibercept. Mean CS improved from 1.40±0.14 log units at baseline to 1.46±0.15 log units at week 20 (P<0.001). VA improved with mean logarithm of the minimum angle of resolution BCVA of 0.33±0.19 at baseline compared with logarithm of the minimum angle of resolution BCVA of 0.28±0.16 at week 20 (P=0.0016). Mean CRT decreased from 324±85 to 289±61 µm (P<0.001). Twenty-two (55%) patients experienced an overall improvement in National Eye Institute 25-Item Visual Function Questionnaire score. Interestingly, an association was found between changes in CS and change in CRT (r2=0.385, P<0.001) and between changes in BCVA and change in CRT (r2=0.092, P=0.032).ConclusionSwitching from ranibizumab to aflibercept in patients with recalcitrant diabetic macular edema resulted in an improvement in all measured metrics, including CS, VA, and CRT. A majority of patients also indicated an improvement in vision-related quality of life. The finding of a stronger relationship between changes in CRT and CS compared with changes in CRT and BCVA suggests that the inclusion of CS as an endpoint may yield a more complete understanding of visual outcomes than that obtained by using VA alone.

Efficacy of oral moxidectin against susceptible and resistant isolates of Dirofilaria immitis in dogs

BackgroundMonthly topical and sustained-release injectable formulations of moxidectin are currently marketed; however, an oral formulation, while approved at a dose of 3 μg/kg, is not currently marketed in the United States. Although resistance of heartworms to all macrocyclic lactone (ML) heartworm preventives (ivermectin, milbemycin, selamectin and moxidectin) has been demonstrated, to date no data have been reported on the effectiveness of oral moxidectin against recent isolates of Dirofilaria immitis.MethodsA total of nine studies were conducted to determine the efficacy of moxidectin against a range of older and recently sourced heartworm isolates. Dogs (groups of three to eight) were inoculated with 50 D. immitis infective larvae (L3) from nine different isolates (MP3, Michigan, JYD-34, ZoeMO-2012, ZoeKy-2013, ZoeLA-2013, GCFL-2014, AMAL-2014 and ZoeAL-2015) and treated 28–30 days later with single oral doses of 3 μg/kg of moxidectin. Additionally, one group of dogs that was inoculated with JYD-34 was treated monthly for 3 consecutive months beginning 30 days post inoculation. Dogs were held for approximately 4 months after the initial (or only) treatment and then necropsied for recovery of adult heartworms.ResultsA single dose of 3 μg/kg of moxidectin was 100% effective in preventing the development of five of nine heartworm isolates (MP3, Michigan, ZoeKy, GCFL and ZoeAL isolates), confirming their susceptibility to oral moxidectin at this dose. MP3 and Michigan are isolates sourced from the field more than 9 years ago, while ZoeKy, ZoeAL and GCFL were isolated from the field within the past 2 to 3 years. Against JYD-34, ZoeMO, ZoeLA and AMAL isolates, a single dose of 3 μg/kg of moxidectin was not completely effective, with efficacies of 19%, 82%, 54% and 62%, respectively, demonstrating resistance of these heartworm isolates to oral moxidectin at this dosage. Three consecutive monthly doses of 3 μg/kg of moxidectin were also incompletely effective against the JYD-34 isolate, with an efficacy of 44%. JYD-34 was originally isolated in 2010, while ZoeMO, ZoeLA and AMAL were isolated within the past 2 to 3 years.ConclusionsA single oral dose (3 μg/mg) of moxidectin was 100% effective in preventing the development of ML-susceptible heartworm isolates while being incompletely effective against ML-resistant isolates.

Evaluation of contrast sensitivity and other visual function outcomes in neovascular age-related macular degeneration patients after treatment switch to aflibercept from ranibizumab.

PurposeThis study evaluated visual function and anatomic and vision-related quality-of-life outcomes in recalcitrant neovascular age-related macular degeneration (AMD) subjects switched to aflibercept (Eylea®) from ranibizumab (Lucentis®).MethodsIn a single-center study conducted in Barrie, ON, 40 patients with persistent fluid despite previous ranibizumab treatment were switched to aflibercept with 3 consecutive monthly doses. Main outcome measure was mean change from baseline to week 12 in Pelli–Robson contrast sensitivity (CS). Secondary outcomes were mean change in best corrected visual acuity (BCVA), central retinal thickness (CRT), and National Eye Institute 25-Item Visual Function Questionnaire (NEI VFQ-25) score. A two-sided paired t-test was used in the statistical data analysis to compare the means of continuous variables.ResultsForty-nine eyes (baseline visual acuity [VA] >6/120) were evaluated. Ranibizumab injections (mean ± standard deviation [SD] 28.2±22.1 [range 3–86]) were administered prior to treatment switch. Mean CS improved from 1.32 at baseline to 1.40 log units at week 12. VA was stable throughout. Mean CRT decreased from 354 µm at baseline to 332 µm at week 12 (−22 µm, P=0.004). Twenty-six (65%) patients experienced an overall improvement in NEI VFQ-25 score. Interestingly, a correlation was observed between improvement in log CS and CRT change (P=0.000046).ConclusionContrast sensitivity improved statistically and significantly, and CRT decreased from baseline to week 12 after a switch to aflibercept from ranibizumab. Analysis of CS as an independent outcome end point in neovascular AMD treatment switch studies may provide a more complete understanding of visual response.

Pro re Nata versus Bimonthly Regimen in Exudative AMD Treated with Aflibercept: 1-year Results

Purpose To compare pro re nata (PRN) and bimonthly intravitreal aflibercept injection protocols in the treatment of neovascular age-related macular degeneration (nAMD). Methods This was a retrospective, observational, comparative study in 2 centers. All study patients presented with newly diagnosed nAMD and were treated as follows after an induction of 3 consecutive monthly loading doses: the bimonthly group was retreated every 2 months and followed up every 4 months while the PRN group was retreated in case of subretinal exudation or visual acuity decrease and followed up every month. A comprehensive ophthalmic examination was performed at each study visit. Results At 1 year, 34 eyes were analyzed. The 19 patients in the bimonthly group had a mean visual acuity improvement of +8.5 Early Treatment Diabetic Retinopathy Study (ETDRS) letters whereas stabilization was observed in the PRN group (-0.47 ETDRS letters; p = 0.027). All patients in the bimonthly group had 4 follow-up visits and 7.5 injections whereas the mean number of follow-up visits in the PRN group (15 patients) was 7.8 with 7.6 injections. Conclusions Our study suggests that a fixed bimonthly aflibercept retreatment protocol may provide better visual results than a PRN protocol.

OHP-036 Ajusted indirect comparison of intravitreal aflibercept versus intravitreal bevacizumab in wet-age related macular degeneration

BackgroundNo head-to-head clinical trials have been published comparing aflibercept and bevacizumab for the neovascular form of age-related macular degeneration (AMD). Adjusted indirect comparisons may provide useful information on the relative...

Progression of leprosy disability after discharge: is multidrug therapy enough?

ObjectiveTo evaluate the risk factors related to worsening of physical disabilities after treatment discharge among patients with leprosy administered 12 consecutive monthly doses of multidrug therapy (MDT/WHO).MethodsCohort study was carried out at the Leprosy Laboratory in Rio de Janeiro, Brazil. We evaluated patients with multibacillary leprosy treated (MDT/WHO) between 1997 and 2007. The Cox proportional hazards model was used to estimate the relationship between the onset of physical disabilities after release from treatment and epidemiological and clinical characteristics.ResultsThe total observation time period for the 368 patients was 1 570 person-years (PY), averaging 4.3 years per patient. The overall incidence rate of worsening of disability was 6.5/100 PY. Among those who began treatment with no disability, the incidence rate of physical disability was 4.5/100 PY. Among those who started treatment with Grade 1 or 2 disabilities, the incidence rate of deterioration was 10.5/100 PY. The survival analysis evidenced that when disability grade was 1, the risk was 1.61 (95% CI: 1.02–2.56), when disability was 2, the risk was 2.37 (95% CI 1.35–4.16), and when the number of skin lesions was 15 or more, an HR = 1.97 (95% CI: 1.07–3.63). Patients with neuritis showed a 65% increased risk of worsening of disability (HR = 1.65 [95% CI: 1.08–2.52]).ConclusionImpairment at diagnosis was the main risk factor for neurological worsening after treatment/MDT. Early diagnosis and prompt treatment of reactional episodes remain the main means of preventing physical disabilities.

Pilot Trial of Rituximab for the Prevention of Epstein Barr Virus B Cell Lymphoproliferative Disorder (EBV-LPD) Following T Cell Depleted (TCD) Unrelated or HLA-Mismatched Related Hematopoietic Stem Cell Transplantation.

The risk of developing an EBV-LPD is highest in recipients of an unrelated or HLA-mismatched related TCD HCT, with a reported incidence of 10–23%. Although treatment with anti-B cell monoclonal antibodies and/or adoptive immunotherapy can be curative, these therapies are not always effective and can cause fatal tumor lysis syndrome. We have previously shown that the risk of developing an EBV-LPD after a TCD HCT is greatest within the first 2 to 6 months post HCT, and in patients whose circulating CD4 cell counts are less than 200/ul. We therefore developed a phase I pilot trial to investigate the feasibility of 6 monthly doses of rituximab for the prevention of EBV-LPD. Eligibility included hepatitis B surface antigen negative recipients of a TCD HCT from an unrelated or HLA mismatched related donor, EBV seropositive donor and/or host, ANC of >1500 cells/ul, documentation of remission, negative EBV viremia at baseline, and lack of ongoing infection at the time of enrollment. Patients received a maximum of 6 consecutive monthly doses of rituximab (375 mg/m2/dose) starting approximately 1 month post HCT. Less than six monthly doses were given if the patient developed a circulating CD4 cell count > 200/ul sooner than 7 months post transplant. To date, 22 patients (4–68 years of age, median 19.5 years) have been enrolled on this IRB approved trial, 20 of whom have completed therapy. Rituximab was well tolerated. The main side effect potentially related to rituximab was reversible neutropenia (n=5), which resulted in cessation of treatment as per protocol after the 2nd (n=1), 3rd (n=1), or 4th (n=1) dose. To date, none of the 22 patients on trial have developed an EBV-LPD compared to 10.1% of patients who received an unrelated or HLA MM-related TCD HCT during the same time interval but did not receive prophylactic rituximab. Although 2 patients had prolonged shedding of parainfluenza virus (n=1) or RSV (n=1) from the upper respiratory tract, there was no significant increase in viral or bacterial infections in patients who received rituximab prophylaxis. No patient on trial developed a fatal infection. Eighteen of 22 patients enrolled on trial are alive at a median of 14.5 months post HCT. One patient died of GVHD and 3 high risk patients succumbed to relapse. In evaluable patients, recovery of normal numbers of circulating B cells occurred between 5 and 12 months after the last dose of rituximab. This trial suggests that monthly rituximab can be safely given during the first 6 months after a TCD HCT, resulting in a decreased incidence of EBV-LPD. Larger trials investigating the optimum number and timing of Rituximab doses required to prevent this complication are needed as are studies evaluating recovery of specific B cell function in recipients of rituximab after allogeneic HCT.