A plain language summary describing how two different concentrations of GP2017, a biosimilar adalimumab medicine, are associated with similar drug levels within the body.

WHAT IS THIS SUMMARY ABOUT?: This plain language summary explains, in simple terms, the results of a study from 2022 discussing a biosimilar medicine called GP2017 (called SDZ-ADL in this summary, sold as Hyrimoz®). This medicine is used to treat people with inflammatory conditions. This study investigated a new, high-concentration formulation of GP2017 (SDZ-ADL-HCF) in order to show that the high concentration option acts the same way in the body as SDZ-ADL. SDZ-ADL-HCF has been submitted for regulatory approval to health authorities on the basis of this study and was recently approved by the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for people with the inflammatory conditions that SDZ-ADL is used to treat. This newly developed formulation provides the option for receiving injections less often with reduced volumes which can have a positive impact on the injection experience and increase patient convenience. WHAT WAS THE AIM OF THE CURRENT STUDY?: This study looked at the pharmacokinetics of SDZ-ADL and SDZ-ADL-HCF, meaning it compared how the active medicine behaved in the body at different times after the injection of each of the formulations. The study also looked at how each formulation was recognized by the body's immune system (known as immunogenicity), and the side effects associated with each formulation. This study was randomly assigned and double-blinded, meaning that neither the participants nor the researchers knew which formulation each participant received. This reduces the risk of bias in the results. WHAT WERE THE FINDINGS FROM THE CURRENT STUDY?: The study found that an injection of SDZ-ADL-HCF resulted in similar amounts of the medicine being present within the blood as an injection of SDZ-ADL. This information was needed for the approval of SDZ-ADL-HCF. Participants also experienced similar immune reactions and the number of participants with side effects was similar between both concentrations of medicine. The results confirmed that SDZ-ADL-HCF behaves in the same way in the body and is expected to have the same treatment effects as SDZ-ADL, while at the same time offering an improved formulation with a more positive injection experience and increased patient convenience.

GP2017-HCF, a high concentration formulation, demonstrates similar pharmacokinetics, immunogenicity and safety to GP2017, an approved adalimumab biosimilar.

BACKGROUND: GP2017 is an adalimumab biosimilar. The objective of this study is to compare the pharmacokinetics (PK) of GP2017 in its approved formulation and GP2017-high concentration formulation (HCF) in a randomized, double-blind, two-arm PK bridging study. RESEARCH DESIGN AND METHODS: Healthy male subjects received a single 40 mg subcutaneous injection of either GP2017-HCF (n = 162) or GP2017 (n = 168). PK, safety, and immunogenicity were assessed over 72 days post-injection. RESULTS: The 90% confidence intervals [CIs] of geometric mean ratios between GP2017-HCF and GP2017 for Cmax, AUC0-inf, AUC0-360 and AUC0-last were within the pre-defined margin of 0.80 to 1.25; thus, PK comparability between GP2017-HCF and GP2017 was demonstrated. Subgroup analysis of PK comparability by anti-drug antibody (ADA) subpopulation showed that the 90% CIs of geometric mean ratios between GP2017-HCF and GP2017 for Cmax, AUC0-inf, AUC0-360 and AUC0-last were within the margin of 0.80 to 1.25 in ADA-positive and ADA-negative subjects. The proportions of subjects with positive ADA responses and with neutralizing antibodies were comparable between the GP2017-HCF and GP2017 groups. GP2017-HCF and GP2017 were well tolerated, and there were no reports of deaths or other serious adverse events. CONCLUSION: Results show PK comparability between GP2017-HCF and GP2017 and comparable safety and tolerability.

Bioequivalence of two formulations of montelukast sodium 4 mg oral granules in healthy adults.

Montelukast is an effective and well-tolerated treatment for the prophylaxis and chronic treatment of asthma, acute prevention of exercise-induced bronchoconstriction and symptomatic relief of seasonal allergic rhinitis and perennial allergic rhinitis. The aim of the study was to compare bioavailability, and characterise the pharmacokinetic profile and safety of Sandoz generic montelukast 4 mg oral granules relative to Singulair(®) mini (Merck, Sharp & Dohme). An open-label, randomised, single-dose, two-treatment, two-period, two-sequence, two-way crossover bioequivalence study was conducted in healthy male volunteers aged 18-55 years, under fasting conditions. The duration of the clinical part of the trial was ≈ 11 days. Montelukast levels in plasma were quantified using a validated liquid chromatography tandem mass spectrometry method, and pharmacokinetic parameters calculated from the drug concentration-time profile using a non-compartmental model. A total of 40 subjects completed both study periods. The ratio test/reference of geometric least squares means was calculated for both formulations of montelukast for the In-transformed pharmacokinetic parameters; the 90% confidence intervals (CIs) were within the pre-defined limits of 80.00-125.00%: 92.2% (90% CI: 87.42-97.30%) for Cmax, 98.1% (90% CI: 94.49-101.81%) for AUC0-t and 97.6% (90% CI: 94.14-101.27%) for AUC0-∞. Two study subjects each reported one mild adverse event: dyspepsia (possibly related to study medication) and throat pain (not considered related to study medication). Sandoz montelukast 4 mg oral granules are bioequivalent to Singulair(®) 4 mg mini oral granules, with a similar safety profile. This suggests that these two preparations can be considered interchangeable in clinical practice.

Validated composite assessment scales for the global face.

BACKGROUND: Twenty grading scales have been developed to assess age-related facial changes. Until now, the validity with regard to the patient's actual age and the clinical importance of combined measurement tools to describe facial aging was unclear. OBJECTIVE: To investigate the reliability and validity of a total face score and three global face assessment scales for estimated age, estimated aesthetic treatment effort, and signs of aging in the facial units. MATERIALS AND METHODS: Descriptive, reliability, correlation, and principal component analyses based on the assessment of 50 subjects by 12 raters using the 20 grading scales and the global face assessment scales. RESULTS: Inter- and intrarater reliability was high for the total face score and for the scales on estimated age and aesthetic treatment effort. Actual age was highly correlated with these three measures. Facial aging was indicated particularly by scales of the lower face. CONCLUSION: The aesthetic grading scales and global scales on estimated age and aesthetic treatment effort are reliable and valid instruments. The results suggest that a more-comprehensive evaluation of the human face and its age-related changes can help to identify important areas of facial aging and to define optimal aesthetic treatment strategies.

Validated assessment scales for the upper face.

BACKGROUND: Age-related upper face changes such as wrinkles, lines, volume loss, and anatomic alterations may affect quality of life and psychological well-being. The development of globally accepted tools to assess these changes objectively is an essential contribution to aesthetic research and routine clinical medicine. OBJECTIVE: To establish the reliability of several upper face scales for clinical research and practice: forehead lines, glabellar lines, crow's feet (at rest and dynamic expression), sex-specific brow positioning, and summary scores of forehead and crow's feet areas and of the entire upper face unit. METHODS AND MATERIALS: Four 5-point photonumerical rating scales were developed to assess glabellar lines and sex-specific brow positioning. Twelve experts rated identical upper face photographs of 50 subjects in two separate rating cycles using all eight scales. Responses of raters were analyzed to assess intra- and interrater reliability. RESULTS: Interrater reliability was substantial for all upper face scales, aesthetic areas, and the upper face score except for the brow positioning scales. Intrarater reliability was high for all scales and resulting scores. CONCLUSION: Except for brow positioning, the upper face rating scales are reliable tools for valid and reproducible assessment of the aging process.

Neuroferritinopathy: a window on the role of iron in neurodegeneration.

Neuroferritinopathy is a recently recognised genetic disease resulting in a dominantly inherited movement disorder. The condition was mapped by linkage analysis to chromosome 19q13.3 and found to be due to a single adenine insertion in the ferritin light chain (FTL) gene at position 460-461 which is predicted to alter the C terminus of the FTL polypeptide. Clinical features of neuroferritinopathy are highly variable, with chorea, dystonia, and Parkinsonian features predominating in different affected individuals. The most consistent feature is a dystonic dysarthria. Symptoms and abnormal physical signs appear to be restricted to the nervous system and onset is typically in the fourth to sixth decades. Low serum ferritin also characterises this condition. Brain MR imaging of affected patients demonstrates iron deposition in the basal ganglia, progressing over years to cystic degeneration, and brain histochemistry shows abnormal aggregates of ferritin and iron. Now that the molecular basis of the condition is known, therapeutic interventions to reduce or reverse brain iron deposition are being evaluated. This rare disease provides evidence of a central role for iron metabolism in neurodegenerative disorders.