Efficacy and safety of candidate biosimilar CT-P41 versus reference denosumab: a double-blind, randomized, active-controlled, Phase 3 trial in postmenopausal women with osteoporosis.

This 78-week (18-month) study conducted in 479 postmenopausal women with osteoporosis evaluated the efficacy, pharmacodynamics, pharmacokinetics, safety, and immunogenicity of candidate biosimilar CT-P41 relative to US reference denosumab. CT-P41 had equivalent efficacy and pharmacodynamics to US-denosumab, with similar pharmacokinetics and comparable safety and immunogenicity profiles. PURPOSE: To demonstrate equivalence of candidate biosimilar CT-P41 and US reference denosumab (US-denosumab) in postmenopausal women with osteoporosis. METHODS: This 78-week (18-month), double-blind, randomized, active-controlled Phase 3 study (NCT04757376) comprised two treatment periods (TPs). In TPI, patients (N = 479) were randomized 1:1 to 60 mg subcutaneous CT-P41 or US-denosumab. At Week 52, those who had received CT-P41 in TPI continued to do so. Those who had received US-denosumab were randomized (1:1) to continue treatment or switch to CT-P41 in TPII. The primary efficacy endpoint was percent change from baseline in lumbar spine bone mineral density at Week 52. Efficacy equivalence was concluded if associated 95% confidence intervals (CI) for least squares (LS) mean group differences fell within ± 1.503%. The primary pharmacodynamic (PD) endpoint was area under the effect curve for serum carboxy-terminal cross-linking telopeptide of type I collagen through the first 26 weeks, with an equivalence margin of 80-125% (for 95% CIs associated with geometric LS mean ratios). RESULTS: Equivalence was demonstrated for CT-P41 and US-denosumab with respect to primary efficacy (LS mean difference [95% CI]: - 0.139 [- 0.826, 0.548] in the full analysis set and - 0.280 [- 0.973, 0.414] in the per-protocol set) and PD (geometric LS mean ratio [95% CI]: 94.94 [90.75, 99.32]) endpoints. Secondary efficacy, PD, pharmacokinetics, and safety results were comparable among all groups up to Week 78, including after transitioning to CT-P41 from US-denosumab. CONCLUSIONS: CT-P41 was equivalent to US-denosumab in women with postmenopausal osteoporosis, with respect to primary efficacy and PD endpoints.

Pityriasis Rubra Pilaris - a difficult path to optimal treatment. Case report.

Pityriasis Rubra Pilaris is a rare, chronic inflammatory dermatosis of unknown etiology, presenting with erythema and papular eruptions. Treatment is difficult due to the lack of causal therapy, guidelines and requires an individualized approach. The most common treatments are systemic retinoids, immunosuppressants, phototherapy and biological therapy. This article presents the case of a 73-year-old man suffering from type 1 pityriasis rubra pilaris. The patient was initially treated with acitretin, which was discontinued due to hypogammaglobulinemia. This rare side effect of acitretin has not been previously published. As a second-line treatment, the patient received methotrexate, but with no clinical improvement after 3 months and an increase in skin pruritus. Finally, the use of isotretinoin resulted in significant clinical improvement and was well tolerated.

Causes of falls in women in Krakow population.

INTRODUCTION: Falls rank among the most serious medical problems in elderly persons, having psychological as well as social consequences. With several hundred fall risk factors known at present, it is necessary to select those that occur most frequently in a particular population. Only then will it be possible to implement effective fall prevention programmes with the aim of increasing awareness of the causes and consequences of falls in elderly persons. The aim of the study was to identify the profile of circumstances of falls in the population of women from Krakow above 50 years of age. MATERIAL AND METHODS: This paper presents the results of a pilot study carried out as a telephone survey. RESULTS: The study population of 50 women experienced 77 falls. The results served to estimate that over half of the women fell once in a year, with most falls occurring in summer as well as during the day. Among the environmental causes of falls outdoors, over 70% were attributable to slippery ground and uneven surface. 56% of the women were taking antihypertensive and cardiovascular drugs and 54% received at least two medications at the same time. Environmental causes were more important than health-related causes of falls. CONCLUSIONS: 1. A fall is most frequently the result of several causes. 2. While the study data need to be verified against a bigger study population, they are an important source and basis for further studies.

Epidemiology, clinical significance, costs and fall prevention in elderly people.

Falls are the fifth most frequent cause of death among elderly people. They are one of the main causes of disability and reduction in the quality of life in this age group. Falls are the direct cause of the majority of limb and femoral neck fractures. Fall prevention is a difficult, expensive and underestimated problem in Poland. 30-40% of women aged 65 years or older experience a fall at least once a year. Falls lead directly to fractures in 5% of those living on their own and 20% of hospital inpatients. Underlying a fall are dysfunctions of multiple organs and the influence of external factors. About 400 different fall risk factors have been described. It has been demonstrated that the risk of falls can be decreased by as much as 40% provided that the patient is treated by a multidisciplinary team of specialists. Standard procedures of care have already been developed in Europe and in the world. This paper presents current knowledge on the epidemiology, significance and costs of treatment of complications of falls in elderly people.

Multiple invasive cervical resorption and celiac disease: A case report.

Multiple invasive cervical resorption (MICR) is a rare disease of unknown etiology. A case of a patient with MICR of six teeth, with low vitamin D3 level detected, is presented. Applied surgical and general treatments were only partially effective, as they failed to stop the resorption, although the parameters of calcium-phosphate management appreciably improved, and secondary hyperparathyroidism was successfully resolved.

Current guidelines for using physiotherapy to prevent falls.

Falls are one of the primary causes of reduced quality of life, disability, and mortality in the elderly. 90-100% of limb fractures in this population result from falls. Preventing falls is a difficult problem, and unfortunately not fully appreciated in Poland. One in three people aged 65 and over experience a fall at least once a year. In the case of community-dwelling individuals, 5% of falls lead to fractures, while among those living in nursing homes and hospitals this figure reaches 20%. Malfunctions of many internal organs and systems can contribute to falls, so that 400 different risk factors have been described; therefore, fall prevention should be multi-dimensional. At the current state of knowledge even a 40% decrease in fracture risk would be possible, provided that the patient is treated by a multidisciplinary team (family practitioner, rheumatologist, orthopedic surgeon, neurologist, physiotherapist, psychologist). Guidelines have already been developed on this subject in Europe and around the world. The present study reviews current opinions on osteoporosis and fall prevention, based on recent literature.

Fracture risk prediction in outpatients from Krakow Region using FRAX tool versus fracture risk in 11-year follow-up.

INTRODUCTION: FRAX is a an algorithm accepted by WHO for evaluating fragility fracture risk of women aged 40 years or more. The aim of this study was to use the FRAX tool to verify the risk of fractures in a population of women from the Cracow region in an 11-year follow-up. MATERIALS AND METHODS: The study was a retrospective cohort survey evaluating the incidence of fragility fractures over 11 years of follow-up. 5,092 women aged 50 years and more were randomly chosen from a group of 100,000 female patients of the Cracow Medical Centre who came to the Centre for densitometric examination between 1997 and 2001. Finally, 1024 patients were randomized into the study. After an average of 11 years a follow-up telephone survey was conducted among a randomly selected group of patients using a questionnaire corresponding to the one applied in the first survey. 10-year fracture risk was calculated for each patient using FRAX based on the BMI (Body Mass Index) and for 886 women using FRAX based on BMD (Bone Mineral Density) at the femoral neck. The Polish version of FRAX was validated by comparing the predicted risk with the actual incidence of fractures during the 11-year follow-up. RESULTS: The 10-year probability of a major osteoporotic fracture calculated using FRAX based on BMI for the entire group was 5.3% (median, 1st/3rd quartile: 3.5-8.5%) and the probability of a proximal femur (hip) fracture was 1.3% (median, 1st-3rd quartile: 0.7% -2.4%). In 886 women whose BMD T-score at the femoral neck was available, the mean probability of a major osteoporotic fracture was 4.9% (3.3-7.9%) and of a hip fracture 0.9% (0.3-2.3%). The actual absolute fracture risk calculated on the basis of the number of patients who had experienced a fracture during the follow-up was surprisingly much higher than the predicted figure. The risk of a major fracture in the study group was 17.7% and of a proximal femur fracture, 3%. CONCLUSION: In our opinion, FRAX is a very good screening tool, but not a precise diagnostic tool.