Linaclotide is Effective and Safe for Treating Pediatric Functional Constipation

Linaclotide, a guanylate cyclase C agonist approved for chronic idiopathic constipation and irritable bowel syndrome with constipation in adults, was evaluated for its efficacy and safety in children aged 6-17 with functional constipation. 
This phase 3, randomized, double-blind, placebo-controlled trial was conducted across 64 sites in seven countries. A total of 330 participants meeting modified Rome III criteria were randomly assigned to receive linaclotide 72 μg or placebo once daily for 12 weeks. The primary outcome was the change in spontaneous bowel movement (SBM) frequency, and the secondary outcome was stool consistency over the treatment period.
Out of 330 enrolled patients, 328 were analyzed (164 per group). Baseline SBM rates were 1.28 per week for placebo and 1.16 for linaclotide, increasing to 2.29 and 3.41 SBMs per week, respectively. Linaclotide significantly improved SBM frequency compared to placebo (LSM change: 2.22 vs. 1.05 SBMs per week; difference: 1.17; 95% CI: 0.65-1.69; p < 0.0001) and stool consistency (LSM change: 1.11 vs. 0.69; difference: 0.42; 95% CI: 0.21-0.64; p = 0.0001). 
The most common adverse event was diarrhea, reported in 4% of the linaclotide group compared to 2% of placebo. One case of severe diarrhea led to hospitalization but resolved without complications. No deaths occurred. 
Linaclotide demonstrated efficacy and tolerability in treating pediatric functional constipation and is now approved by the FDA for this indication.
 

Probiotics Combined with Laxatives found Effective for Treating Pediatric Functional Constipation

A network meta-analysis found a combination of probiotics and laxative effective at treating pediatric functional constipation. 
Pediatric constipation affects 0.7% to 29.6% of children globally, with functional constipation accounting for 95% of cases. Despite its prevalence, pharmacological treatments have limited efficacy, with a 60% success rate. Probiotic supplements have shown potential benefits in randomized controlled trials (RCTs), though the probiotic strains used varied significantly across studies. 
This network meta-analysis (NMA) aimed to evaluate the efficacy and acceptability of various probiotic supplements in managing pediatric functional constipation. The analysis included nine RCTs with 710 participants (mean age: 5.5 years; 49.4% girls), assessing the impact of probiotics, alone or with laxatives, on bowel movement frequency and treatment acceptability.
Results demonstrated that most probiotics, whether used individually or with laxatives, significantly improved bowel movement and stool frequency compared to placebo/control. Protexin combined with laxatives showed the greatest improvement (SMD = 1.87, 95% CI: 0.85 to 2.90), outperforming all other products. Among single probiotic treatments, only Lactobacillus casei rhamnosus Lcr35 achieved significant efficacy compared to placebo/control (SMD = 1.37, 95% CI: 0.32 to 2.43). All probiotic products had similar rates of fecal incontinence and dropouts as the control groups. 
This NMA supports the use of combined probiotics and laxatives for pediatric functional constipation, provided no contraindications exist, and highlights the importance of specific probiotic strains in treatment efficacy.
 

Adjunctive efficacy of Bifidobacterium animalis subsp. lactis XLTG11 in alleviating functional constipation in children

According to a recent study, the administration of XLTG11 at a dosage of 1 × 1010 CFU per day to children resulted in an elevation in fecal frequency, brought about favorable alterations in gut microbiota, and effectively regulated short-chain fatty acid (SCF) genes and genes associated with methane metabolism. This study’s results were published in the Brazilian Journal of Microbiology. 
In this double-blinded, randomized trial, eligible children were divided into two groups: the intervention group (n = 65) received conventional treatment with probiotics, and the control group (n = 66) received conventional treatment without probiotics. The primary outcome measure focused on fecal frequency. To predict gene family abundances based on 16S information, fecal gut microbiota analysis and PICRUSt (Phylogenetic Investigation of Communities by Reconstruction of Unobserved States) were utilized.
During the treatment period, there was a significant increase in the weekly frequency of feces in each group (F = 41.97, p < 0.001). The frequency of feces (times/week (t/w)) in the intervention group was notably higher compared to the control group post-intervention (3.69 ± 2.62 t/w versus 3.18 ± 1.43 t/w for the first week, 4.03 ± 2.54 t/w versus 2.89 ± 1.39 t/w for the second week, 3.74 ± 2.36 t/w versus. 2.94 ± 1.18 t/w for the third week, and 3.45 ± 1.98 versus 3.17 ± 1.41 t/w for the fourth week) (F = 7.60, p = 0.0067). The dominant species shifted to Bifidobacterium breve, Bifidobacterium longum, and Escherichia coli in the group that received the intervention. The genes associated with short-chain fatty acid metabolism were upregulated, while methane metabolism was downregulated.
The above study demonstrated that giving children XLTG11 at a daily dose of 1 × 1010 CFU resulted in more frequent bowel movements, brought about positive changes in gut microbiota, and effectively controlled SCFs genes and genes associated with methane metabolism.
 

R21/Matrix-M vaccine well-tolerated and efficacious against malaria in children

A recent study found that R21/Matrix-M vaccine which is low-cost, was well tolerated and offered high efficacy against clinical malaria in children. The results of this study were published in the journal, Lancet.

This double-blind, randomised, phase 3 trial of the R21/Matrix-M malaria vaccine screened 5477 children (aged 5-36 months), out of which 1705 and 3434 children were randomly assigned in a 2:1 ratio to the control vaccine and R21/Matrix-M (5 μg R21 plus 50 μg Matrix-M), respectively. The vaccines were administered 4 weeks apart as 3 doses, with a booster dose administered 12 months after the third dose. Half of the participants were recruited at the seasonal malaria transmission sites and the other half at standard sites with perennial malaria transmission. The primary objective of the study was to assess the protective efficacy of R21/Matrix-M, 14 days following the third vaccination. Vaccine efficacy, safety, and immunogenicity were also assessed.

At the end of the study, it was found that R21/Matrix-M vaccine was well tolerated. The most frequent adverse events were injection site pain (301 out of 1615 participants) and fever (754 out of 1615 participants). At the end of 12 months, the vaccine efficacy at the seasonal sites and standard sites were 75% and 67%, respectively. The effectiveness of the vaccine was correlated with antibodies produced by the vaccination against the conserved central Asn-Ala-Asn-Pro (NANP) repeat sequence of the circumsporozoite protein. The 5-17 month age group of children showed higher NANP-specific antibody titres when compared to the 18-36 month age group.

From the above results, it can be concluded that R21/Matrix-M vaccine which is low-cost, may be well tolerated and may offer high efficacy against clinical malaria in children.

Safety and efficacy of linaclotide in treating functional constipation in paediatric patients

According to a recent study, linaclotide has proven to be an effective and well-tolerated remedy for functional constipation in pediatric patients. This study’s findings were published in the journal, Lancet. Gastroenterology & hepatology.

In this double-blind, randomised,  placebo-controlled, phase 3 study, patients aged 6-17 years were randomly assigned to receive either oral linaclotide 72 μg [n=166] or placebo [n=164] once daily for 12 weeks. The study's primary efficacy endpoint was the change from baseline (CFB) in the frequency rate of spontaneous bowel movements (SBM) per week over a twelve-week period. The change from baseline in stool consistency during the treatment period was the secondary efficacy endpoint. Efficacy and safety were analyzed in all patients who received at least one dose of the study intervention.

The mean frequency rate for SBMs was 1·28 SBMs per week (SD 0·87) with placebo and 1·16 SBMs per week (0·83) with linaclotide at baseline. This rate increased to 2·29 SBMs per week (1·99) with placebo and 3·41 SBMs per week (2·76) with linaclotide during the intervention. Patients treated with linaclotide demonstrated a significant increase in SBM frequency [least-squares mean (LSM) CFB 2·22 SBMs per week (SE 0·19)] compared to those on placebo [LSM CFB 1·05 SBMs per week (0·19)]. Additionally, linaclotide demonstrated a notable improvement in stool consistency compared to the placebo group [LSM CFB 1.11 (SE 0.08) versus 0.69 (0.08)]. Based on the above results, it can be concluded that linaclotide is an efficacious and well-tolerated treatment for functional constipation in paediatric patients.