Three-year outcomes of individualized ranibizumab treatment in patients with diabetic macular edema: the RESTORE extension study.

OBJECTIVE: To evaluate long-term efficacy and safety profiles during 3 years of individualized ranibizumab treatment in patients with visual impairment due to diabetic macular edema (DME). DESIGN: Phase IIIb, multicenter, 12-month, randomized core study and 24-month open-label extension study. PARTICIPANTS: Of the 303 patients who completed the randomized RESTORE 12-month core study, 240 entered the extension study. METHODS: In the extension study, patients were eligible to receive individualized ranibizumab treatment as of month 12 guided by best-corrected visual acuity (BCVA) and disease progression criteria at the investigators' discretion. Concomitant laser treatment was allowed according to the Early Treatment Diabetic Retinopathy Study guidelines. Based on the treatments received in the core study, the extension study groups were referred to as prior ranibizumab, prior ranibizumab + laser, and laser. MAIN OUTCOME MEASURES: Change in BCVA and incidence of ocular and nonocular adverse events (AEs) over 3 years. RESULTS: Overall, 208 patients (86.7%) completed the extension study. In patients treated with ranibizumab during the core study, consecutive individualized ranibizumab treatment during the extension study led to an overall maintenance of BCVA and central retinal subfield thickness (CRST) observed at month 12 over the 2-year extension study (+8.0 letters, -142.1 µm [prior ranibizumab] and +6.7 letters, -145.9 µm [prior ranibizumab + laser] from baseline at month 36) with a median of 6.0 injections (mean, 6.8 injections; prior ranibizumab) and 4.0 (mean, 6.0 injections; prior ranibizumab + laser). In the prior laser group, a progressive BCVA improvement (+6.0 letters) and CRST reduction (-142.7 µm) at month 36 were observed after allowing ranibizumab during the extension study, with a median of 4.0 injections (mean, 6.5 injections) from months 12 to 35. Patients in all 3 treatment groups received a mean of <3 injections in the final year. No cases of endophthalmitis, retinal tear, or retinal detachment were reported. The most frequently reported ocular and nonocular adverse effects over 3 years were cataract (16.3%) and nasopharyngitis (23.3%). Eight deaths were reported during the extension study, but none were suspected to be related to the study drug/procedure. CONCLUSIONS: Ranibizumab was effective in improving and maintaining BCVA and CRST outcomes with a progressively declining number of injections over 3 years of individualized dosing. Ranibizumab was generally well tolerated with no new safety concerns over 3 years.

Similar Efficacy of Mesalazine in Adult and Older Adult Ulcerative Colitis Patients: Post Hoc Analysis of a Randomized Noninferiority Trial of 1600 mg vs 400 mg Tablets.

BACKGROUND: The efficacy data on treatment in older adults are scarce, while the greatest increase in ulcerative colitis (UC) prevalence is observed in age groups of individuals 40 to 65 years of age and ≥65 years of age. AIM: We assessed the difference in rates of clinical and endoscopic response and remission in UC adults (≤60 years) and older adults (>60 years) treated with mesalazine. METHODS: We performed a post hoc analysis of data from a phase 3 noninferiority trial of 817 UC patients treated with mesalazine for 8 and additional 26 weeks in a double-blind and open-label study, respectively. We used Wilcoxon rank sum or chi-square test to analyze differences between groups and multivariable logistic regression to determine the associations between endoscopic remission as outcome (Mayo endoscopic subscore [MES] = 0 or ≤1) and independent variables including disease duration, baseline MES, age, sex, comedications, and comorbidities. RESULTS: Older adults had a longer disease duration, a higher number of comorbidities, concomitant medications, and higher baseline MES (2.38 ±â€…0.486 in older adults vs 2.26 ±â€…0.439 in adults; P = .008) compared with adults. We observed no difference in rates of combined clinical and endoscopic remission, clinical remission and response, and endoscopic remission and response at week 8 and 38 post-treatment. In addition to other well-known predictors of worse outcome, patients with ≥3 comedications were less likely to achieve an MES = 0 at week 8 and 38 and an MES ≤1 at week 38. CONCLUSIONS: We observed similar efficacy of mesalazine in adult and older adult UC patients. The increased comedication number rather than age may decrease effectiveness of UC medications, highlighting the importance of healthy aging.

We investigated the rates of clinical and endoscopic response in adult (≤60 years) and older adult (>60 years) ulcerative colitis patients treated with oral mesalazine; our results demonstrated that age did not influence the efficacy and safety.

Two-year safety and efficacy of ranibizumab 0.5 mg in diabetic macular edema: interim analysis of the RESTORE extension study.

OBJECTIVE: To evaluate the 2-year safety and efficacy of ranibizumab 0.5 mg in diabetic macular edema (DME). DESIGN: Twenty-four-month, open-label, multicenter, Phase IIIb extension study. PARTICIPANTS: Two hundred forty of 303 patients with visual impairment due to DME who completed the RESTORE core study and entered the extension. METHODS: All patients were eligible to receive ranibizumab 0.5 mg pro re nata (PRN) from month 12 (end of core study) to month 36 based on best-corrected visual acuity (BCVA) stability and disease progression retreatment criteria. Patients were also eligible to receive laser PRN according to Early Treatment Diabetic Retinopathy Study guidelines. A preplanned interim analysis was performed at month 24, stratifying by treatment groups as in the RESTORE core study and referred to as prior ranibizumab, ranibizumab plus laser, or laser groups in the extension. MAIN OUTCOME MEASURES: Incidence of ocular and nonocular adverse events (AEs) and mean change in BCVA. RESULTS: Two hundred twenty patients (92%) completed the month 24 visit. Over 2 years, the most frequent ocular serious AE (SAE) and AE were cataract (2.1%) and eye pain (14.6%), respectively. The main nonocular AEs were nasopharyngitis (18.8%) and hypertension (10.4%). There were no cases of endophthalmitis, and the incidences of nonocular SAEs were low. Of the patients entering the extension, 4 deaths were reported in the second year, none of which were related to study drug or procedure. Mean BCVA gain, central retinal thickness (CRT) decrease, and National Eye Institute Visual Functioning Questionnaire-25 (NEI VFQ-25) composite score observed at month 12 were maintained at month 24 (prior ranibizumab: +7.9 letters, -140.6 µm, and 5.6, respectively; prior ranibizumab plus laser: +6.7 letters, -133.0 µm, and 5.8, respectively), with an average of 3.9 (prior ranibizumab) and 3.5 ranibizumab injections (prior ranibizumab plus laser). In patients treated with laser alone in the core study, the mean BCVA, CRT, and NEI VFQ-25 composite score improved from month 12 to month 24 (+5.4 letters, -126.6 µm, and 4.3, respectively), with an average of 4.1 ranibizumab injections. CONCLUSIONS: Ranibizumab 0.5 mg administered according to prespecified visual stability and disease progression criteria was well tolerated, with no new safety concerns identified over 2 years. Overall, an average of 3.8 ranibizumab injections was sufficient to maintain (prior ranibizumab) or improve (prior laser) BCVA, CRT, and NEI VFQ-25 outcomes through the second year. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

The RESTORE study: ranibizumab monotherapy or combined with laser versus laser monotherapy for diabetic macular edema.

OBJECTIVE: To demonstrate superiority of ranibizumab 0.5 mg monotherapy or combined with laser over laser alone based on mean average change in best-corrected visual acuity (BCVA) over 12 months in diabetic macular edema (DME). DESIGN: A 12-month, randomized, double-masked, multicenter, laser-controlled phase III study. PARTICIPANTS: We included 345 patients aged ≥18 years, with type 1 or 2 diabetes mellitus and visual impairment due to DME. METHODS: Patients were randomized to ranibizumab + sham laser (n = 116), ranibizumab + laser (n = 118), or sham injections + laser (n = 111). Ranibizumab/sham was given for 3 months then pro re nata (PRN); laser/sham laser was given at baseline then PRN (patients had scheduled monthly visits). MAIN OUTCOME MEASURES: Mean average change in BCVA from baseline to month 1 through 12 and safety. RESULTS: Ranibizumab alone and combined with laser were superior to laser monotherapy in improving mean average change in BCVA letter score from baseline to month 1 through 12 (+6.1 and +5.9 vs +0.8; both P<0.0001). At month 12, a significantly greater proportion of patients had a BCVA letter score ≥15 and BCVA letter score level >73 (20/40 Snellen equivalent) with ranibizumab (22.6% and 53%, respectively) and ranibizumab + laser (22.9% and 44.9%) versus laser (8.2% and 23.6%). The mean central retinal thickness was significantly reduced from baseline with ranibizumab (-118.7 µm) and ranibizumab + laser (-128.3 µm) versus laser (-61.3 µm; both P<0.001). Health-related quality of life, assessed through National Eye Institute Visual Function Questionnaire (NEI VFQ-25), improved significantly from baseline with ranibizumab alone and combined with laser (P<0.05 for composite score and vision-related subscales) versus laser. Patients received ∼7 (mean) ranibizumab/sham injections over 12 months. No endophthalmitis cases occurred. Increased intraocular pressure was reported for 1 patient each in the ranibizumab arms. Ranibizumab monotherapy or combined with laser was not associated with an increased risk of cardiovascular or cerebrovascular events in this study. CONCLUSIONS: Ranibizumab monotherapy and combined with laser provided superior visual acuity gain over standard laser in patients with visual impairment due to DME. Visual acuity gains were associated with significant gains in VFQ-25 scores. At 1 year, no differences were detected between the ranibizumab and ranibizumab + laser arms. Ranibizumab monotherapy and combined with laser had a safety profile in DME similar to that in age-related macular degeneration.

Efficacy and safety of dexmethylphenidate extended-release capsules administered once daily to children with attention-deficit/hyperactivity disorder.

OBJECTIVE: This 5-week, multicenter, double-blind, placebo-controlled, parallel-group investigation is the first fixed-dose study to evaluate efficacy and tolerability of three doses of (10, 20, or 30 mg, once daily [o.d.]) dexmethylphenidate hydrochloride (HCl) extended-release (d-MPH XR; Focalin XR) across multiple settings to treat pediatric attention-deficit/hyperactivity disorder (ADHD). RESULTS: ADHD pediatric outpatients (n = 253) diagnosed according to Diagnostic and Statistical Manual of Mental Disorders, 4(th) edition, criteria were randomized (1:1:1:1) to receive d-MPH XR (10, 20, or 30 mg o.d.) or placebo. Treatment with d-MPH XR significantly (p < 0.001) reduced the mean score (change from baseline) on Conners'-ADHD/DSM-IV Scales (CADS) as assessed by the teacher CADS-T (dose [mean];10 mg [18], 20 mg [16.9], 30 mg [20.7]) and parents, CADS-P (dose [mean];10 mg [15.8]; 20 mg [17.8]; 30 mg [20.5]) compared to placebo (mean CADS-T [5.7]; CADS-P [4.6]). A significant (p < 0.001) proportion of patients in the three d-MPH XR treatment groups showed improvement on the clinician-rated, Clinical Global Impressions-Improvement (CGI-I) scales (10 mg [73.8%]; 20 mg [71.2%]; 30 mg [77.2 %]) and severity ratings (CGI-S) compared to the placebo group (CGI-I, 22.2%). Adverse events were mild to moderate in severity and similar to previous observations for this class of neurostimulants. CONCLUSION: All three doses of d-MPH XR (10, 20, or 30 mg o.d), were significantly more effective than placebo in improving ADHD symptoms as confirmed by the teacher, parent and clinician. Additionally, d-MPH XR was well tolerated and demonstrated a consistent safety profile.