Effectiveness and safety of adalimumab biosimilar in patients with inflammatory bowel disease.

BACKGROUND: Adalimumab biosimilar MSB11022 (Idacio ®) has been approved for the same indications as its originator (Humira ®), based on findings from clinical trials in plaque psoriasis. Data on its efficacy and safety in inflammatory bowel disease, however, are scarce. METHODS: Retrospective, observational study of 44 patients with inflammatory bowel disease: 30 were treated with originator adalimumab, 5 were directly started on MSB11022, and 9 switched from originator to biosimilar adalimumab. To evaluate the effectiveness of the use of adalimumab in inflammatory bowel disease, both laboratory markers (fecal calprotectin and C-reactive protein) and scales that measure the activity of inflammatory bowel disease using specific scales (Harvey-Bradshaw Index (HBI) have been usEd.) for Crohn's disease and Mayo Score for Ulcerative Colitis. Efficacy was evaluated by recording the adverse effects that could occur with the administration of adalimumab (original or biosimilar). The success of the switch was determined by analyzing meaningful differences in effectiveness and safety criteria. Concomitant therapy and the need for dose intensification were also analyzed. Objective of this study was to assess the effectiveness and safety of biosimilar adalimumab in adalimumab-naïve patients and patients switched from originator adalimumab. RESULTS: No significant differences were observed in clinical disease activity (P=.317) or biochemical parameters [fecal calprotectin (P=.445) and C-reactive protein P=.661)] after the switch from the originator adalimumab to MSB11022. There was not a significant reduction in the concomitant use of corticosteroids and thiopurines (P=.157). No emergency room visits or hospitalizations were observed during the study period and none of the patients experienced serious adverse effects. CONCLUSIONS: Between originator adalimumab and biosimilar-start cohorts, no differences were observed, between originator adalimumab and switch cohorts, no significant differences were found either, and with the pre- and post-switch to biosimilar comparison, 2 of the 9 patients experienced AEs after the switch. The biosimilar showed a favorable safety profile (one patient with a serious adverse effect (rash) with biosimilar discontinued treatment) and no significant changes to clinical or biochemical parameters were observed after the switch.

A comparison of patient-reported outcome measures for dupuytren disease: A prospective view.

Treatment success in Dupuytren´s disease has traditionally been assessed by clinical examination and physical measures, but based on patient orientation, patient-reported outcome measures (PROMs) can be used to quantify treatment impacts and health-related quality of life. The aim of this study was to compare the most widely used PROMS in Dupuytren´s disease, their psychometric properties, and their association with objectively measured hand function. We show a prospective study in which two disease-specific questionnaires (URAM scale and SDSS) and two hand-specific questionnaires (briefMHQ and PEM) were administered before and a month after the treatment with collagenase. Psychometric properties (construct validity, internal consistency, test-retest reliability, internal and external responsiveness, reliability, and minimal clinically important difference (MCID)) were calculated for all the questionnaires. Ninety-two completed both sets of questionnaires. Pre- and post-treatment scores were strongly correlated (Spearman rho >0.6) for all questionnaires. High internal consistency (Cronbach alpha >0.88) was observed for all the questionnaires. Test-retest reliability was also significant, with an ICC of >0.50 in all cases. The MCID was similar for three of the questionnaires (URAM, 11.528/45=0.256; SDSS, 5.079/20=0.254; and PEM, 21.542/77=0.215) and somewhat lower for the briefMHQ (10.617/60=0.177). No correlations were observed between treatment outcome and treated hand (r = 0.107; p = 0.31), joint (r = 0.163; p = 0.12), or finger (r = -0.151; p = 0.15). In conclusion, we did not find that any one questionnaire performed better than the other in detecting perceived changes in health status among patients with Dupuytren´s disease treated with collagenase.

Sensitivity and Specificity of the Unité Rhumatologique Des Affections De La Main (URAM) Scale for Dupuytren Contracture: A Systematic Review and Meta-Analyses.

BACKGROUND: Unité Rhumatologique des Affections de la Main (URAM) is a novel and disease-specific questionnaire for Dupuytren contracture, a fibroproliferative disease that affects hands causing progressive contracture in flexion of the fingers. OBJECTIVES: To evaluate the sensitivity and specificity of the URAM scale in Dupuytren contracture. MATERIALS AND METHODS: We performed meta-analyses of 10 articles published in PubMed, Embase, Cochrane, Google Scholar, Latin American and Caribbean Health Sciences Literature (LILACS), and in various grey literature databases that describe the use of the URAM and Tubiana scales to assess treatment outcomes in Dupuytren contracture. We built three models: a hierarchical summary receiver operating characteristic (HSROC) model to determine the optimal threshold for defining Dupuytren contracture, a difference in means model to assess the magnitude of the effect of different treatment modalities, and a meta-regression model to determine the effect on patient quality of life questionnaires such as the URAM, according to variations in Tubiana scores after treatment. RESULTS: The HSROC and bivariate models showed a sensitivity of 80.23% (95% CI: 75.66 to 84.14) and an overall specificity of 2.61% (95% CI: 1.11 to 6.05). The second model showed an overall difference in means of 1.95 (95% CI: -2.86 to -1.04) for partial fasciectomy and collagenase Clostridium histolyticum (CCH) injections, and -1.30 (95% CI: -1.77 to -0.83) for partial fasciectomy, and -2.75 (95% CI: -4.73 to -0.78) for CCH. The coefficient obtained in the meta-regression model was -1.666 (95% CI: -4.183 to 0.851). CONCLUSION: The URAM scale is highly sensitive to changes in Dupuytren contracture but has low specificity. It also showed a strong correlation with worsening of finger contracture as measured by the Tubiana scale.

"Validation of a spanish version of the 'Unité Rhumatologique Des Affections De La Main' (URAM) scale".

BACKGROUND: In health care, quality-of-life surveys and questionnaires related to care are becoming increasingly important as a measure of its quality. There is currently no Spanish version of the Unité Rhumatologique des Affections de la Main (URAM) scale, which makes it suitable for hand pathology. The purposes of this study are to develop a Spanish version of the URAM and perform a transcultural adaptation of it, analyzing the result for reliability, validity, and sensitivity to changes. METHODS: The questionnaire was evaluated for patients with Dupuytren's disease and Carpal Tunnel Syndrome. The cohort study subjects were interviewed at three points in time (baseline, three days after intervention, and one month after), administering the QuickDASH, URAM, and SF-12 (CF12 = physical component, CM12 = mental component) questionnaires at baseline and after intervention; and only the URAM at 3 days. Content validity was evaluated using Cronbach's α. The distribution of the factorial loads of the items and the pattern of the answers were checked. Responsiveness was evaluated by the size of the effect and the reliable rate of change. Convergent and divergent validity was performed using Spearman's r between the different questionnaires. RESULTS: The study was conducted with 106 patients. The mean baseline scores were: URAM = 14.8, QuickDASH = 41.6, CF12 = 39.3 and CM12 = 49.4. Ceiling or floor effects were not observed in the Spanish URAM. The Cronbach α = 0.853 explains 49.6% of the variance. The study had a high reproducibility (intraclass correlation coefficient (ICC) = 0.939). Size effect, measured as differences in scores, was moderate for URAM (-0.69) and QuickDASH (-0.51); and low for CF12 and CM12. The correlation of URAM with QuickDASH was high (r = 0.716), and moderate with DD and CTS. CONCLUSION: The Spanish version of the URAM is a valid and reliable tool for use in assessing hand pathology.

Toxicity and effectiveness of carboplatin in obese or overweight patients.

OBJECTIVE: To evaluate the efficiency and toxicity of carboplatin using actual body weight in obese/overweight patients using the Calvert formula with Cockcroft-Gault for CrCl estimation. METHODS: We evaluated the association of BMI in regards to efficiency and toxicity in a retrospective cohort study of patients who started treatment with carboplatin between 2012 and 2013. Cohorts included obese/overweight patients and normal-weight patients. Efficiency was measured by overall survival, progression-free survival and response rate. Toxicity was measured by the proportion of dose reductions and delays of chemotherapy cycles. We utilized a bivariate and multivariate analysis. RESULTS: Eighty-six patients were included in the study (50% obese/overweight). There was not a statistically significant difference in effectiveness and toxicity between the two groups in BMI. In the multivariate analysis, BMI not was associated with overall survival (hazard ratio: 0.95, 95% CI: 0.54-1.66, p = 0.849), progression-free survival (hazard ratio: 0.91; 95% CI: 0.54-1.54; p = 0.732), cycle delays (odds ratio (OR): 1.47, 95% CI: 0.80-2.69, p = 0.218) or carboplatin dose reductions (OR: 0.87, 95% CI: 0.35-2.15, p = 0.760). Response rate was 53.5% in both groups. CONCLUSIONS: In our study, obese and overweight cancer patients did not show a statistically significant difference in terms of effectiveness and toxicity compared to normal-weight cancer patients who were treated with carboplatin using their actual body weight with the Calvert formula and Cockcroft-Gault for CrCl estimation. Therefore, it was appropriate to use the actual body weight for our patients.

Variability of carboplatin dose calculation methods in Spain.

OBJECTIVE: To describe and analyze the variability in carboplatin dosing strategies in Spanish hospitals. METHODS: We designed a questionnaire consisting of 19 multiple-choice items structured in two sections (hospital characteristics and carboplatin dosing data). The questionnaire was sent by e-mail to all the oncology pharmacists included in the register of the Spanish Oncology Pharmacy Group (GEDEFO), and we analyzed the completed questionnaires. RESULTS: Response rate was 33.5% from a total of 185 pharmacy services invited to take part in the survey. All hospitals used the Calvert formula to calculate carboplatin dose with glomerular filtration rate estimated by a formula, most commonly the Cockcroft-Gault equation (80.7%). Carboplatin doses were capped in most hospitals (91.9%): 54.8% capped creatinine clearance at 125 mL/min, 11.3% capped serum creatinine, and 19.3% capped both creatinine clearance and serum creatinine. Serum creatinine cut-off values ranged from 0.36 mg/dL to 1 mg/dL. The most commonly used body weight was actual body weight for underweight, normal weight, and overweight patients. The use of adjusted ideal body weight increased in obese and especially in morbidly obese patients. CONCLUSION: The results from this survey show the variability that exists in carboplatin dose calculation methods among Spanish hospitals and the need to continue investigating to find the optimum dose calculation method and unify criteria to avoid differences between sites that can affect effectiveness and toxicity of carboplatin-containing treatments.

Effectiveness of Intracameral Phenylephrine in Achieving Mydriasis and Reducing Complications During Phacoemulsification: A Systematic Review and Meta-Analysis.

PURPOSE: To compare the effectiveness of intracameral phenylephrine and topical mydriatics in achieving mydriasis and protecting against complications during phacoemulsification. METHODS: A systematic search of the literature comparing the mydriatic effect and surgical safety profile of intracameral phenylephrine and topical mydriatics in phacoemulsification was conducted in the Medline, Embase, Lilacs, Web of Science, Cochrane, ClinicalTrials.gov , and Teseo databases. The search targeted clinical trials, cohort studies, and case-control studies published between April 20, 2003 and August 14, 2016. Mydriatic effect was assessed by difference in means in pupil of all the patients in the studies [mean difference (MD)] and intraoperative complications were assessed by using inverse-variance weighted odds ratios (ORs), with adjustment for dose. A meta-regression analysis was also conducted, with adjustment for dose, use of epinephrine, tamsulosin use, and type of surgery and type of intraocular lens. RESULTS: We found 7 articles about mydriatic effect and another 7 about complications. Intracameral phenylephrine achieved a similar mydriatic effect to topical mydriatics, with a difference of less than 10% (MD -0.74 mm, 95% CI: -1.67 to 0.18, I2 = 95.8%, P < 0.0001). The pooled OR for complications was OR 0.50, 95% CI: 0.19-1.31, I2 = 0.0%, P = 0.670, and posterior capsular rupture was the most common complication in the different studies analyzed. CONCLUSION: Intracameral phenylephrine achieves a similar mydriatic effect to topical mydriatics (difference <15%) and is associated with a not-significant effect on reducing the odds of intraoperative complications.

Intraoperative complications of phacoemulsification in pseudoexfoliation: Metaanalysis.

This review analyzed the effect of pseudoexfoliation (PXF) syndrome on the risk for surgical complications during phacoemulsification. Peer-reviewed literature in Medline, Embase, Lilacs, Web of Science, and Cochrane databases was systematically searched, along with gray literature in the Teseo and National Institutes of Health clinical trials database. Clinical trial, cohort, case-control, and cross-sectional studies comparing phacoemulsification complications in patients with and without PXF were identified, and 22 of 30 studies were selected for analysis. Odds ratios (ORs) for posterior capsule rupture or zonular dialysis were calculated and pooled using random-effects models. A random-effects meta-regression model was also generated. Using the random-effects model, the pooled OR was 2.1363 (95% confidence interval, 1.5394-2.9648), which corresponds to a risk of more than 10%. No significant changes to this risk were observed in the cumulative or stratified analyses. Although advances in surgical technique have been made, PXF syndrome continues to be a risk factor in phacoemulsification. FINANCIAL DISCLOSURE: No author has a financial or proprietary interest in any material or method mentioned.