A switch from originator-adalimumab to the biosimilar SB5 in patients with Crohn's disease: an analysis of two propensity score-matched cohorts.

BACKGROUND/AIMS: Originator-adalimumab, an established treatment for patients with Crohn's disease (CD), showed no difference in efficacy or adverse events versus adalimumab biosimilar SB5 (SB5-adalimumab) over 10 weeks (W) of treatment. To understand the long-term effectiveness of SB5-adalimumab in CD, patients switched from originator-adalimumab to SB5-adalimumab were compared with patients remaining on originator-adalimumab over 104 W. METHODS: Data on patients aged ≥18 years, diagnosed with CD and treated at ISCARE, were collected prospectively from July 2018 to January 2021. Primary outcome: clinical disease activity at W52, measured by Harvey-Bradshaw index (HBI). Secondary outcomes: C-reactive protein (CRP), faecal calprotectin (FC) and adalimumab concentrations at W10, 26, 52 and 104, and treatment persistence. To ensure comparable cohorts, patients were propensity score (PS)-matched for age, gender and disease activity. RESULTS: After matching, 54 patients remained per cohort. At W52, mean (SD) HBI score was 3.2 (2.5) for originator-adalimumab and 4.0 [3.6] for SB5-adalimumab (difference [95% CI] -0.78 [-2.8, 1.3]; n = 18/cohort); no clinically meaningful differences in CRP, FC or drug concentrations were noted. Kaplan-Meier's estimates (95% CI) of remaining on treatment were originator-adalimumab: 0.870 (0.785-0.965) versus SB5-adalimumab: 0.648 (0.533-0.789) at W52 and significantly lower for SB5-adalimumab versus originator-adalimumab (p < .001) over 104 W. Local skin reaction events/pain was the main reason for treatment discontinuation in the SB5-adalimumab cohort (n = 20/54 [37%]). CONCLUSIONS: These long-term results of CD patients receiving originator-adalimumab or following nonmedical switch to SB5-adalimumab show similar therapeutic effects on clinical disease activity, biological parameters and pharmacokinetic profile in both cohorts from 52 to 104 W. A separation in persistence was observed beyond W26, mainly due to differences in local reactions at the injection site.

Infliximab Biosimilar (Remsima™) in Therapy of Inflammatory Bowel Diseases Patients: Experience from One Tertiary Inflammatory Bowel Diseases Centre.

BACKGROUND: The evidence on the efficacy and safety of biosimilar infliximab (IFX) in patients with inflammatory bowel diseases (IBD) is sparse. METHODS: Consecutive IBD patients visiting our centre were included. One cohort composed of prospectively followed patients who were switched from original to biosimilar IFX between January and March 2015. The second cohort included retrospectively assessed anti-tumor necrosis factor α-naïve patients who started therapy between January 2015 and January 2016. Disease activity was assessed using standard clinical indices, endoscopic evaluation, and laboratory parameters (blood count, C-reactive protein (CRP) and fecal calprotectin (FC)). Trough levels and anti-drug antibodies (ATIs) were also measured. Patients were evaluated 56 weeks (W56) after switch and at week 14 (W14) and week 46 (W46) in the naïve cohort. RESULTS: Seventy-four IBD patients were switched to biosimilar IFX and 119 naïve patients newly initiated therapy with the preparation. Disease activity remained stable in a majority of switched patients (remission at week 0 (W0) vs. W56: 72.2 vs. 77.8%; median difference of both Harvey-Bradshaw index and Simple Clinical Colitis Activity Index between W0 and W56 was 0). When W0 and W56 were compared, no significant difference in CRP (4.3 ± 8.0 vs. 3.3 ± 3.8 mg/l; p = 0.89) and FC (135 ± 153 vs. 199 ± 225 µg/g; p = 0.17) was observed. In total, 92% of Crohn's disease (CD) and 83% of ulcerative colitis (UC) patients responded to induction therapy (W14) with biosimilar IFX. At W46, the response rate was 86% in CD and 64% in UC. Moreover, half of UC patients experienced mucosal healing at W14 and improvement of perianal disease occurred in 95% of CD at W46. In this cohort, clear steroid-sparing effect was observed. No increase in immunogenicity was found in switched patients (ATI positivity: 9.5 vs. 6.0%, p = 0.54) and the type and frequency of adverse events were comparable to the original preparation in both cohorts. CONCLUSION: Switching of IBD patients from original to biosimilar IFX is effective and safe.

Twice-daily dapagliflozin co-administered with metformin in type 2 diabetes: a 16-week randomized, placebo-controlled clinical trial.

AIMS: To evaluate the efficacy and safety of twice-daily dosing of dapagliflozin and metformin, exploring the feasibility of a fixed-dose combination. METHODS: In this 16-week, phase III, randomized, double-blind placebo-controlled study, adults who were receiving metformin administered twice daily (≥1500 mg/day) and had inadequate glycaemic control were randomized 1:1:1:1 to receive dapagliflozin twice daily (2.5 or 5 mg), placebo or dapagliflozin 10 mg once daily (which was included as a benchmark). The primary endpoint was change from baseline glycated haemoglobin (HbA1c) level. Secondary endpoints included changes in fasting plasma glucose (FPG) level and body weight. RESULTS: Four hundred adults were randomized to dapagliflozin (2.5 mg twice daily, 5 mg twice daily, 10 mg once daily) or placebo co-administered with metformin twice daily. At 16 weeks, the adjusted mean change in HbA1c from baseline was significantly reduced in the dapagliflozin 2.5 mg twice daily and 5 mg twice daily groups versus placebo (-0.52 vs. -0.30%, p = 0.0106 and -0.65% vs. -0.30%, p < 0.0001). There were also significantly greater improvements for dapagliflozin twice daily groups versus placebo in FPG body weight and achievement of HbA1c level of <7%. Efficacy outcomes for dapagliflozin twice daily were numerically similar to those for dapagliflozin once daily. Dapagliflozin twice daily was well tolerated. CONCLUSIONS: Dapagliflozin 2.5 or 5 mg twice daily added to metformin was effective in reducing glycaemic levels in patients with type 2 diabetes inadequately controlled with metformin alone. This study supports the development of a fixed-dose combination regimen.

Effect of dapagliflozin in patients with type 2 diabetes who have inadequate glycaemic control with glimepiride: a randomized, 24-week, double-blind, placebo-controlled trial.

AIMS: Progressive deterioration of glycaemic control in type 2 diabetes mellitus (T2DM) often requires treatment intensification. Dapagliflozin increases urinary glucose excretion by selective inhibition of renal sodium-glucose cotransporter 2 (SGLT2). We assessed the efficacy, safety and tolerability of dapagliflozin added to glimepiride in patients with uncontrolled T2DM. METHODS: This 24-week, randomized, double-blind, placebo-controlled, parallel-group, international, multicentre trial (ClinicalTrials.gov NCT00680745) enrolled patients with uncontrolled T2DM [haemoglobin A1c (HbA1c) 7-10%] receiving sulphonylurea monotherapy. Adult patients (n = 597) were randomly assigned to placebo or dapagliflozin (2.5, 5 or 10 mg/day) added to open-label glimepiride 4 mg/day for 24 weeks. Primary endpoint was HbA1c mean change from baseline at 24 weeks. Secondary endpoints included change in body weight and other glycaemic parameters. RESULTS: At 24 weeks, HbA1c adjusted mean changes from baseline for placebo versus dapagliflozin 2.5/5/10 mg groups were -0.13 versus -0.58, -0.63, -0.82%, respectively (all p < 0.0001 vs. placebo by Dunnett's procedure). Corresponding body weight and fasting plasma glucose values were -0.72, -1.18, -1.56, -2.26 kg and -0.11, -0.93, -1.18, -1.58 mmol/l, respectively. In placebo versus dapagliflozin groups, serious adverse events were 4.8 versus 6.0-7.1%; hypoglycaemic events 4.8 versus 7.1-7.9%; events suggestive of genital infection 0.7 versus 3.9-6.6%; and events suggestive of urinary tract infection 6.2 versus 3.9-6.9%. No kidney infections were reported. CONCLUSIONS: Dapagliflozin added to glimepiride in patients with T2DM uncontrolled on sulphonylurea monotherapy significantly improved HbA1c, reduced weight and was generally well tolerated, although events suggestive of genital infections were reported more often in patients receiving dapagliflozin.

Switching From Originator Adalimumab to the Biosimilar SB5 in Patients With Inflammatory Bowel Disease: Short-term Experience From a Single Tertiary Clinical Centre.

BACKGROUND AND AIMS: Patients' perspectives after switching from originator to biosimilar adalimumab have yet to be assessed. We evaluated the efficacy of switching from the originator adalimumab to a biosimilar compound [SB5] in patients with inflammatory bowel disease [IBD]. METHODS: Data on IBD patients who were switched from the originator to biosimilar adalimumab [SB5] at IBD Center ISCARE were analysed. Disease activity was assessed using standard clinical indices (Harvey-Bradshaw index [HBI] for Crohn's disease [CD] and partial Mayo score for ulcerative colitis [UC]), and laboratory parameters (C-reactive protein [CRP] and faecal calprotectin [FC]). Trough levels and anti-drug antibodies were measured. Patients were evaluated 10 weeks [W10] after the switch, and results were compared with the control group of patients on originator compound. RESULTS: A total of 93 patients switched to biosimilar adalimumab were included [CD 86%] and were matched to 93 controls for age, gender, diagnosis, and disease activity. There was no difference in the disease activity in either SWITCH or ORIGINATOR cohorts between Weeks 0 and 10. Similarly, no difference was found between cohorts at both prespecified time points. Moreover, no significant differences in CRP or FC concentrations were seen between W0 and W10 either in the SWITCH, or in the ORIGINATOR cohort [p >0.05]. Adalimumab serum trough levels remained stable after the switch. No new safety signals were detected. CONCLUSIONS: Our study confirmed that switching IBD patients from the originator adalimumab to a biosimilar compound [SB5] does not affect treatment efficacy.

[Cytological detection of cervical dysplasia and neoplasia]. / Cytologická záchytnost cervikálních dysplazií a neoplazií.

A total of 7017 women were examined during a year in a specialized dispensary for prevention of cervical cancer and in a department of obstetrics. Diagnosis of PAP III or higher was established in 227 smears, i.e. 3,3% of cases. A correlation of positive cytology with following biopsy was performed. The influence of cervical inflammation and virus lesion on possible modification of suspect cytology was discussed.

[Effect of dapagliflozin in patients with type 2 diabetes who have inadequate glycaemic control with glimepiride]. / Effekt von Dapagliflozin bei Typ-2-Diabetikern mit unzureichender Blutzuckereinstellung unter Glimepirid.

AIMS: Progressive deterioration of glycaemic control in type 2 diabetes mellitus (T2DM) often requires treatment intensification. Dapagliflozin increases urinary glucose excretion by selective inhibition of renal sodium-glucose cotransporter 2 (SGLT2). We assessed the efficacy, safety and tolerability of dapagliflozin added to glimepiride in patients with uncontrolled T2DM. METHODS: This 24-week, randomized, double-blind, placebo-controlled, parallel-group, international, multicentre trial (ClinicalTrials.gov NCT00680745) enrolled patients with uncontrolled T2DM [haemoglobin A1c (HbA1c) 7-10 %] receiving sulphonylurea monotherapy. Adult patients (n = 597) were randomly assigned to placebo or dapagliflozin (2.5, 5 or 10 mg/day) added to open-label glimepiride 4 mg/day for 24 weeks. Primary endpoint was HbA1c mean change from baseline at 24 weeks. Secondary endpoints included change in body weight and other glycaemic parameters. RESULTS: At 24 weeks, HbA1c adjusted mean changes from baseline for placebo versus dapagliflozin 2.5/5/10 mg groups were -0.13 versus -0.58, -0.63, -0.82 %, respectively (all p < 0.0001 vs. placebo by Dunnett's procedure). Corresponding body weight and fasting plasma glucose values were -0.72, -1.18, -1.56, -2.26 kg and -0.11, -0.93, -1.18, -1.58 mmol/l, respectively. In placebo versus dapagliflozin groups, serious adverse events were 4.8 versus 6.0-7.1 %; hypoglycaemic events 4.8 versus 7.1-7.9 %; events suggestive of genital infection 0.7 versus 3.9-6.6 %; and events suggestive of urinary tract infection 6.2 versus 3.9-6.9 %. No kidney infections were reported. CONCLUSIONS: Dapagliflozin added to glimepiride in patients with T2DM uncontrolled on sulphonylurea monotherapy significantly improved HbA1c, reduced weight and was generally well tolerated, although events suggestive of genital infections were reported more often in patients receiving dapagliflozin.