Secukinumab in Ankylosing Spondylitis Patients: A Cost-per-Responder Analysis from the Indonesian Health System Perspective.

OBJECTIVE: There are no publications that have demonstrated economic value for ankylosing spondylitis (AS) treatments in Indonesia. Cost per responder (CPR) is a lean method of economic evaluation. We estimated CPR from Indonesia's health system perspective following AS treatment with secukinumab relative to adalimumab, golimumab, and infliximab. METHODS: In the absence of head-to-head trials, a comparative evidence analysis was conducted in the form of matching-adjusted indirect comparison (MAIC) to estimate the response rate of various competing treatment options against secukinumab. This was followed by a CPR analysis that compared the cost per patient for a defined response level. RESULTS: Based on MAIC, patients on secukinumab had higher Assessment in Spondyloarthritis International Society (ASAS) 20 response (improvement of ≥ 20% and ≥ 1 unit in at least three domains on a scale of 10 and no worsening of ≥ 20% and ≥ 1 unit in remaining domain on a scale of 10) and ASAS 40 response (improvement of ≥ 40% and ≥ 2 units in at least three domains on a scale of 10 and no worsening at all in remaining domain) versus those on adalimumab, golimumab, and infliximab at week 24. The cost per ASAS 20 at week 24 for secukinumab was 75% lower than adalimumab, 65% lower than golimumab, and 80% lower than infliximab. The cost per ASAS 40 at week 24 for secukinumab was 77% lower than adalimumab, 67% lower than golimumab, and 83% lower than infliximab. Secukinumab dominated adalimumab, golimumab, and infliximab at week 24 and adalimumab at week 52, by being more efficacious at lower cost. Threshold analysis revealed that substantial reduction in efficacy or increase in cost of secukinumab would make secukinumab not cost effective, indicating the robustness of the results. CONCLUSION: This study demonstrated that if AS patients in Indonesia were treated with secukinumab instead of comparator therapies, more patients could be treated, and more patients would reach response to treatment for the same budget.

The Role of Serum Expression Levels of Microrna-21 on Bone Mineral Density in Hypostrogenic Postmenopausal Women with Osteoporosis: Study on Level of RANKL, OPG, TGFß-1, Sclerostin, RANKL/OPG Ratio, and Physical Activity.

BACKGROUND: MiR-21 is known to play a role in osteoclast proliferation and differentiation, but the role of serum miR-21 expression in osteoporosis remains unclear. Previous research found that serum miR-21 expression was positively correlated with bone mineral density in postmenopausal osteoporosis patients, but other factors involved in postmenopausal osteoporosis still unknown. This study aimed to determine the role of serum miR-21 expression, concentration of RANKL, OPG, TGF-ß1, sclerostin and serum calcium, RANKL/OPG ratio, and physical activity on bone mineral density of spine in hypoestrogenic postmenopausal women with osteoporosis (PMOP) compared with no osteoporosis (PMNOP), with point of interest on the expression of serum miR-21. METHODS: this study was conducted by comparative cross-sectional design. The subjects were divided into 2 groups of PMOP and PMNOP. We used an absolute quantification real-time PCR method to determine serum miR-21 expressions level. RESULTS: Median of serum miR-21 expression at the PMOP group was significantly higher compared to PMNOP group (p = 0.001). Serum miR-21 expression, RANKL, RANKL/OPG ratio, and physical activity were significantly correlated with BMD values in the PMOP group. Moderate physical activity was significantly negatively correlated with serum miR-21 expression. We also obtained a linear regression equation BMD = 1.373-0.085*Ln.miR-21-0.176*Log10.RANKL (R2 = 52.5%). CONCLUSION: serum miR-21 expression in PMOP was higher compared with PMNOP. Serum miR-21 expression proved to have a negative effect on spinal BMD values in hypoestrogenic postmenopausal women with osteoporosis of 8.5%. Obtained equation of BMD = 1.373-0.085*Ln.miR-21-0.176*Log10.RANKL can explain the value of spinal BMD by 52.5%.

A Double-blind, Randomized Controlled Trial of Ciplukan (Physalis angulata Linn) Extract on Skin Fibrosis, Inflammatory, Immunology, and Fibrosis Biomarkers in Scleroderma Patients.

BACKGROUND: scleroderma is an autoimmune disease characterized by organ fibrosis, resistant to standard treatment. It is suspected the addition of Physalis angulata Linn. (Ciplukan) extract as adjuvant therapy can improve the scleroderma skin fibrosis. The aim at this study is to evaluate the effect of ciplukan extract as adjuvant on scleroderma skin fibrosis in standard therapy, based on modified Rodnan skin scale (MRSS), inflammatory biomarkers, immunology and serum fibrosis. METHODS: double-blind, randomized clinical trial was performed in scleroderma patients with stable disease at Cipto Mangunkusumo hospital and Hasan Sadikin hospital during November 2015-March 2017 who met the selection criteria and continued to receive standard therapy. The subjects were randomly allocated into two groups: the study group received the ciplukan  extract 3 x 250 mg / day for 12 weeks and the placebo group. Examination of MRSS, ESR, P1NP, BAFF and sCD40L was performed every 4 weeks until the end of the study. RESULTS: fifty-nine subjects completed the study. They consisted of 29 subjects of the treatment group and 30 of the placebo group, with an average age of 41 (SD 9) years, the proportion of women: male = 9 : 1. There was a significant improvement of skin fibrosis in the study group with a highly significant decrease in MRSS (35.9% VS 6.3%, p <0.001) and a relative decrease in P1NP levels (17.8% VS 0.7%, p = 0.002). No decrease in ESR, BAFF and sCD40L levels in both groups. There was a weak but significant positive correlation between MRSS with P1NP levels (r = 0.236, p = 0.036). CONCLUSION: Ciplukan extract with dose 3 x 250 mg for 12 weeks as adjuvant on scleroderma standard therapy alleviates skin fibrosis significantly based on MRSS and P1NP levels.

Low bone turnover in premenopausal women with type 2 diabetes mellitus as an early process of diabetes-associated bone alterations: a cross-sectional study.

BACKGROUND: Individuals with Diabetes Mellitus (DM) are at increased risk for fracture due to the decrease in bone strength and quality. Serum procollagen type I intact N-terminal (P1NP) and serum C-terminal cross-linking telopeptide of type I collagen (CTX) as markers of bone formation and resorption, respectively, have been reported to be decreased in T2DM. It remains unclear whether diabetes-associated alterations in the bone turnover of T2DM individuals are related to the longer duration of the disease or may occur earlier. Furthermore, previous studies on BTMs in T2DM individuals have mostly been done in postmenopausal women with T2DM, which might have masked the DM-induced alterations of bone turnover with concurrent estrogen deficiency. This study aims to assess the levels of serum P1NP and CTX as markers of bone turnover in premenopausal women with and without T2DM. METHODS: This cross-sectional study involves 41 premenopausal women with T2DM, and 40 premenopausal women without DM. Sampling was done consecutively. P1NP and CTX measurement was done using the electrochemi-luminescence immunoassay (ECLIA) method. Other data collected include levels of HbA1C, ALT, creatinine, eGFR and lipid profile. RESULTS: Median (interquartile range) P1NP in T2DM is 29.9 ng/ml (24.7-41.8 ng/ml), while in non-DM is 37.3 ng/ml, (30.8-47.3 ng/ml; p = 0.007). Median (interquartile range) CTX in T2DM is 0.161 ng/ml (0.106-0.227 ng/ml), while in non-DM is 0.202 ng/ml (0.166-0.271 ng/ml; p = 0.0035). Levels of P1NP and CTX in the T2DM group did not correlate with the duration of disease, age, BMI or the levels of HbA1C. CONCLUSIONS: Premenopausal women with T2DM indeed have lower bone turnover when compared with non-DM controls. This significantly lower bone turnover process starts relatively early in the premenopausal age, independent of the duration of DM. Gaining understanding of the early pathophysiology of altered bone turnover may be key in developing preventive strategies for diabetoporosis.

Bone Metabolism and Fracture Risk in Diabetes Mellitus.

Individuals with Type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM) are at increased risk for fragility fractures. Bone mineral density (BMD) is decreased in T1DM but often normal or even elevated in T2DM when compared with age-matched non-DM populations. However, bone turnover is decreased in both T1DM and T2DM. The pathophysiologic mechanisms leading to bone fragility is multifactorial, and potentially leads to reduced bone formation, altered bone microstructure and decreased bone strength. Interestingly, different antidiabetic treatments may influence fracture risk due to effects on glycemic control, triggering of hypoglycemic events or osteoblastogenesis.

Correlation between receptor activator of nuclear factor-κß ligand (RANKL), and osteoprotegerin (OPG) with cartilage degradation in rheumatoid arthritis patients.

AIM: to analyze the correlation between Receptor activator of nuclear factor-κß ligand (RANKL), Osteoprotegrin (OPG) serum level with cartilage oligomeric matrix protein (COMP) serum level as a marker of cartilage degradation in rheumatoid arthritis patients. METHODS: a cross-sectional study was conducted on the subjects who came to the outpatient clinic of rheumatology in Cipto Mangunkusumo Hospital. Patients were diagnosed based on the American College of Rheumatology (ACR) 1987 revised criteria. All numerical data, both primary data and data transformation were not normally distributed, so we did bivariate analysis with Spearman correlation test. RESULTS: we collected the data of 60 RA patients with majority of the subject had active disease activity (78.3%). Methotrexate was the most widely disease modifying anti-rheumatoid drug (DMARD) used, either as a single drug (51.7%) or in combination with another DMARD (25.1%). Bivariate analysis was revealed that RANKL, OPG, and OPG/RANKL serum level have no significantly correlation with COMP serum level (p=0.52; p=0.25; p=0.2, respectively). CONCLUSION: RANKL and OPG serum level, had no correlation with cartilage degradation in rheumatoid arthritis patients.

The diagnostic value of combined risk factor analysis and radiological imaging in determining osteoporosis in post-menopausal women.

AIM: To determine the diagnostic value of risk factor analysis (age, duration of menopause, body mass index and physical activities) and radiological imaging (Singh index and cortical index of the femoral neck) in diagnosing osteoporosis in post-menopausal women. METHODS: The study was cross sectional on 64 post-menopausal women without secondary risk factor for osteoporosis. They were classified proportionally using the Singh index. Bone density was measured using DEXA (dual x-ray absorptiometry) on the femoral neck and lumbal 2-4 spine areas. The Singh index and cortical index of the femoral neck were evaluated using femoral neck antero-posterior x-ray. Physical activities were measured using a Historical leisure activity questionnaire. Bivariat statistical analysis was conducted using the t-test and chi-square, whereas multivariate analysis was conducted using multinomial logistic regression. RESULTS: There was a significant association (p<0.05) between bone density and age, body weight, height, body mass index, duration of menopause and Singh index. With multinomial logistic regression analysis, it was demonstrated that only Singh index, the duration of menopause and body mass index had the highest sensitivity and specificity. The score system algorithm could be utilized in two steps, the first was to diagnose osteoporosis and the second was to distinguish between osteopenia and normal bone. This score system had a sensitivity of 91.4% and a specificity of 89.6%, a positive prediction value of 91.4% in determining osteoporosis, and a sensitivity of 66.7%, a specificity of 89.1% and a positive prediction value of 70.6% in determining osteopenia, whereas the negative prediction value was 75%. CONCLUSION: The score system algorithm is the best method for determining osteoporosis in post-menopausal women. If there is osteopenia, evaluation using DEXA is then required. The score system algorithm cannot be used to follow up the therapy.

Factors affecting radiographic progression of knee osteoarthritis.

AIM: To determine factors affecting radiographic progression of knee OA. METHODS: A cross sectional study comprise of patients with OA of knee joints. Kellgren and Lawrence (K-L) grading scale was used to evaluate the radiographic progression of knee OA. All of the patient were noted the demographic data including age, gender, duration of illness, body mass index and bone mass density. Lunar DEXA was used to measure total body-BMD (T-BMD), total bone mineral content (T-BMC) and legs-BMD (L-BMD). RESULTS: About 91 patients was enrolled in this study There were significant differences of body mass index (BMI) (p=0.01) between subgroup of knee OA grading. OR between grade 2 and grade 4 for BMI score highest tertile and BMI score lowest tertile were 5.26 (95% CI 0.59-47.20). There were no significant differences for age, sex, and duration of illness, T-BMD, L-BMD and T-BMC between subgroup of knee OA grading. There were a tendency of correlation on increased of age (OR 2.17, 95% CI 0.56-8.41), log-duration of illness, percentage of T-BMD (4% between grade 2 and 4) with increased of knee OA grading. There was a tendency decrease of percentage of L-BMD (of 7%) between grade 3 and 4. CONCLUSION: In this cross sectional model, BMI was significantly associated with increased of knee OA grading or it could be said that BMI was risk factors for radiographic progression of OA. Subjects who already have knee OA and also have high BMI must be careful about the progression of their knee OA.