Changes in BMD T-score from pre-to post-treatment with biosimilar teriparatide: A single-arm, multi-center study.

Introduction: Teriparatide is a recombinant analog of the parathyroid hormone and an anabolic treatment modality for osteoporosis. This study aimed to evaluate the effectiveness of biosimilar teriparatide (CinnoPar®, CinnaGen Co., Iran) in osteoporotic patients after at least one year of treatment. Methods: In this multi-center, single-arm study, 239 eligible patients received subcutaneous injections of biosimilar teriparatide 20 µg once daily for at least one year. The main outcome measure was the change in bone mineral density (BMD) T-score from baseline (pre-treatment) to end of the study (post-treatment). In addition, the change in the fracture risk assessment tool (FRAX) score was calculated to estimate the 10-year probability of major and hip fractures pre-and post-treatment. Results: A total of 239 patients (age, 63 ± 12.14 years; female, 88.28 %) were included, of which 27.62 % (66/239), 14.64 % (35/239), and 57.74 % (138/239) received biosimilar teriparatide for 12-16 months, 17-20 months, and 21-24 months, respectively. From baseline to end of the study, the T-score at the lumbar spine increased from -2.67 ± 1.04 to -2.26 ± 1.11 (mean percent change, 13.07 ± 62.89; p-value<0.001). Similarly, the T-score at femoral neck increased from -2.18 ± 0.87 to -2.09 ± 0.93 (mean percent change, 3.81 ± 31.52; p-value = 0.006). The proportions of patients with maintained or improved BMD T-score at the lumbar spine and femoral neck sites were 85.36 % (204/239) and 69.04 % (165/239), respectively. Similar results were obtained in subgroups of patients with rheumatoid arthritis and those with a history of a previous fracture or parental hip fracture. FRAX scores did not change significantly during the study (p-values of 0.551 and 0.973 at the lumbar spine and femoral neck, respectively). Conclusion: We observed considerable improvements in BMD following treatment with the biosimilar teriparatide for one year or more. The biosimilar teriparatide can be considered as an effective treatment option in female and male patients with osteoporosis.

Significant hypomethylation of MMP9 gene promoter in patients with systemic lupus erythematosus.

OBJECTIVE: Scholars are exploring novel diagnostic and prognostic biomarkers with higher sensitivity and specificity for systemic lupus erythematosus (SLE). In this regard, DNA methylation alterations have aroused attention. The association between the dysfunction of MMP9 and TNFAIP3 genes and SLE has been previously demonstrated. Therefore, in this study, we investigated the methylation level of MMP9 and TNFAIP3 promoters in peripheral blood mononuclear cells (PBMCs) of SLE patients and healthy controls. METHODS: Eighty Iranian SLE patients and 77 healthy individuals were enrolled. The methylation quantification endonuclease-resistant DNA (MethyQESD) method was used to assess methylation levels of MMP9 and TNFAIP3 in extracted DNA of PBMCs. To quantify the diagnostic utility of the promoter methylation level of these genes, the receiver operating characteristic (ROC) curve was constructed. RESULTS: MMP9 promoter was significantly hypomethylated in SLE patients compared with healthy people (p < 0.001), while there was no significant difference in terms of TNFAIP3 promoter methylation levels (p = 0.167). Also, this differential MMP9 methylation was observed in patients with renal involvement and patients without renal involvement (42.07 ± 25.73 vs 56.74 ± 29.71, p = 0.007). ROC analyses indicated that the diagnostic power of the MMP9 promoter methylation level for SLE was 0.839 [95% CI (0.781-0.911)]. Moreover, MMP9 methylation level was negatively correlated with creatinine and anti-dsDNA concentration and positively correlated with C3 and C4 levels. CONCLUSION: The results of this study highlight the application of MMP9 methylation level in PBMCs of SLE patients as a diagnostic biomarker.

Efficacy and safety of the biosimilar denosumab candidate (Arylia) compared to the reference product (Prolia®) in postmenopausal osteoporosis: a phase III, randomized, two-armed, double-blind, parallel, active-controlled, and noninferiority clinical trial.

BACKGROUND/OBJECTIVE: Osteoporosis is a global health concern with an increasing prevalence worldwide. Denosumab is an antiresoptive agent that has been demonstrated to be effective and safe in osteoporotic patients. This study aimed to compare the efficacy and safety of the biosimilar denosumab candidate (Arylia) to the originator product (Prolia®) in postmenopausal osteoporotic patients. METHODS: In this randomized, double-blind, active-controlled, noninferiority trial, postmenopausal osteoporotic patients received 60 mg of subcutaneous Arylia or Prolia® at months 0, 6, and 12 and were followed up for 18 months. The primary endpoint was the noninferiority of the biosimilar product to the reference product in the percentage change of bone mineral density (BMD) in 18 months at the lumbar spine (L1-L4), total hip, and femoral neck. The secondary endpoints were safety assessment, the incidence of new vertebral fractures, and the trend of bone turnover markers (BTMs). RESULTS: A total of 190 patients were randomized to receive either biosimilar (n = 95) or reference (n = 95) denosumab. In the per-protocol (PP) analysis, the lower limits of the 95% two-sided confidence intervals of the difference between Arylia and Prolia® in increasing BMD were greater than the predetermined noninferiority margin of - 1.78 at the lumbar spine, total hip, and femoral neck sites (mean differences [95% CIs] of 0.39 [- 1.34 to 2.11], 0.04 [- 1.61 to 1.69], and 0.41 [- 1.58 to 2.40], respectively). The two products were also comparable in terms of safety, new vertebral fractures, and trend of BTMs. CONCLUSION: The efficacy of the biosimilar denosumab was shown to be noninferior to that of the reference denosumab, with a comparable safety profile at 18 months. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03293108 ; Registration date: 2017-09-19.

APLAR recommendations on the practice of telemedicine in rheumatology.

INTRODUCTION: The COVID-19 pandemic led to rapid and widespread adoption of telemedicine in rheumatology care. The Asia Pacific League of Associations for Rheumatology (APLAR) working group was tasked with developing evidence-based recommendations for rheumatology practice to guide maintenance of the highest possible standards of clinical care and to enable broad patient reach. MATERIALS AND METHODS: A systematic review of English-language articles related to telehealth in rheumatology was conducted on MEDLINE/PubMed, Web Of Science and Scopus. The strength of the evidence was graded using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach as well as the Oxford Levels of Evidence. The recommendations were developed using a modified Delphi technique to establish consensus. RESULTS: Three overarching principles and 13 recommendations were developed based on identified literature and consensus agreement. The overarching principles address telemedicine frameworks, decision-making, and modality. Recommendations 1-4 address patient suitability, triage, and when telemedicine should be offered to patients. Recommendations 5-10 cover the procedure, including the means, data safety, fail-safe mechanisms, and treat-to-target approach. Recommendations 11-13 focus on training and education related to telerheumatology. CONCLUSION: These recommendations provide guidance for the approach and use of telemedicine in rheumatology care to guide highest possible standards of clinical care and to enable equitable patient reach. However, since evidence in telemedicine care in rheumatology is limited and emerging, most recommendations will need further consideration when more data are available.

Clinical course, chest computed tomography severity score and outcome of coronavirus disease 2019 (COVID-19) in patients with rheumatic diseases.

Aim of the work: To assess the clinical manifestations, imaging findings and outcomes of corona virus disease 2019 (COVID-19) in patients with rheumatic diseases. Patients and methods: In a three-center study, patients with rheumatic diseases who developed COVID-19 were included. Patients were classified into two groups, i) inflammatory arthritis including rheumatoid arthritis (RA), spondyloarthritis (SpA) and undifferentiated arthritis, ii) connective tissue diseases (CTDs) including systemic lupus erythematosus (SLE), vasculitis and others. COVID-19 outcomes were assessed based on chest computed tomography severity score (CT-ss), the level of care, the number of patients who died and flare of underlying rheumatic disease. Results: One hundred ninety-six patients with a mean age of 47.9 ± 15.1 years, 73.5% female, were included. Underlying rheumatic diseases were RA (57.7%), SLE and other CTDs (17.9%), SpA (11.2%), vasculitis (11.2%) and undifferentiated arthritis (2%). Myalgia, malaise and fever were the most common clinical manifestations of COVID-19. Pneumonia on computerized tomography (CT), hospitalization, admission in intensive care unit and need to mechanical ventilation were observed in 75.5, 37.2%, 10.7% and 6.6% of patients, respectively. Treatment with nonsteroidal anti-inflammatory drugs (NSAIDs) and glucocorticoids, diabetes and underlying pulmonary disease were predictors of moderate to severe pneumonia and hospitalization. Fifteen (7.6%) patients died. Flare of underlying rheumatic disease occurred in 16.3% of patients. Flare of disease in patients with CTDs was significantly more than other rheumatic diseases. Conclusions: In rheumatic patients, treatment with NSAIDs or prednisolone, diabetes and pulmonary disease are risk factors of moderate to high CT-ss and hospitalization during COVID-19.

Clinical characteristics and long-term outcome of Takayasu arteritis in Iran: a multicentre study

Background/aim: This study aimed to evaluate the demographic, clinical, angiographic and prognostic characteristics of Takayasu arteritis (TA) in Iran. Materials and methods: A total of 75 patients with TA based on the American College of Rheumatology 1990 criteria for TA classification referred to the Rheumatology Centres, were followed-up from 1989 to 2019. Demographic, clinical, angiographic and prognostic characteristics were collected at baseline and last visit. Results: The mean age was 31.9 ± 9.8 years at the disease onset. Female to male ratio was 14. The median latency in diagnosis was 24 months. Pulse discrepancy in the arms, blood pressure discrepancy in the arms, limb claudication, hypertension and constitutional symptoms were the most common clinical features. The most common angiographic type at the time of diagnosis was Type I (42.7%). The most frequent arterial lesion was stenosis (89.4%). Subclavian, carotid and aortic arteries were the most commonly involved arteries. New lesions developed in 28.6% of patients during the 5.25-year follow-up. Vasculitis-induced chronic damage was observed in all patients. Disease activity decreased and vascular damage remained stable throughout the follow-up period. Conclusions: The clinical features and angiographic type of TA in Iran are different from most Asian countries. Differences in angiographic and clinical features may lead to delayed diagnosis. The issue of delay in diagnosis should create awareness among health care providers that TA is not a very rare disease in Iranians and failure to pay attention to warning symptoms may delay the diagnosis.

A phase III, randomized, two-armed, double-blind, parallel, active controlled, and non-inferiority clinical trial to compare efficacy and safety of biosimilar adalimumab (CinnoRA®) to the reference product (Humira®) in patients with active rheumatoid arthritis.

BACKGROUND: This study aimed to compare efficacy and safety of test-adalimumab (CinnoRA®, CinnaGen, Iran) to the innovator product (Humira®, AbbVie, USA) in adult patients with active rheumatoid arthritis (RA). METHODS: In this randomized, double-blind, active-controlled, non-inferiority trial, a total of 136 patients with active RA were randomized to receive 40 mg subcutaneous injections of either CinnoRA® or Humira® every other week, while receiving methotrexate (15 mg/week), folic acid (1 mg/day), and prednisolone (7.5 mg/day) over a period of 24 weeks. Physical examinations, vital sign evaluations, and laboratory tests were conducted in patients at baseline and at 12-week and 24-week visits. The primary endpoint in this study was the proportion of patients achieving moderate and good disease activity score in 28 joints-erythrocyte sedimentation rate (DAS28-ESR)-based European League Against Rheumatism (EULAR) response. The secondary endpoints were the proportion of patients achieving American College of Rheumatology (ACR) criteria for 20% (ACR20), 50% (ACR50), and 70% (ACR70) responses along with the disability index of health assessment questionnaire (HAQ), and safety. RESULTS: Patients who were randomized to CinnoRA® or Humira® arms had comparable demographic information, laboratory results, and disease characteristics at baseline. The proportion of patients achieving good and moderate EULAR responses in the CinnoRA® group was non-inferior to the Humira® group at 12 and 24 weeks based on both intention-to-treat (ITT) and per-protocol (PP) populations (all p values >0.05). No significant difference was noted in the proportion of patients attaining ACR20, ACR50, and ACR70 responses in the CinnoRA® and Humira® groups (all p values >0.05). Further, the difference in HAQ scores and safety outcome measures between treatment arms was not statistically significant. CONCLUSION: CinnoRA® was shown to be non-inferior to Humira® in terms of efficacy at week 24 with a comparable safety profile to the reference product. TRIAL REGISTRATION: IRCT.ir, IRCT2015030321315N1 . Registered on 5 April 2015.

Investigation of Cardiac Complications and their Incidence in Patients with Ankylosing Spondylitis.

INTRODUCTION: Ankylosing Spondylitis (AS) is a chronic inflammatory disease with unknown etiology which involves the sacroiliac and axial joints, but can also cause peripheral conflicts. It also comprises non-joint symptoms such as acute anterior uveitis, cardiac conduction defects, upper lobe pulmonary fibrosis, neurological involvement and renal amyloidosis. MATERIAL AND METHODS: This study was a cross-sectional descriptive and analytical survey. In this study, 50 patients with AS were examined according to the New York Criteria in Army 501 Hospital in Tehran. Physical examinations, laboratory testing and HLA-B27, as well as X-ray of the spine and sacroiliac joint were taken from all subjects and involvement grading was identified. The control group consisted of 40 healthy people with no evidence of disease. The people resembled the study group in terms of age, sex, smoking, presence of high blood pressure, history of ischemic heart disease and also diabetes. RESULTS: The mean age of patients in control and study group was 33.97 and 33.65 years, respectively. 37 (92.5%) patients in the control group and 46 in study group (92%) were male. The mean duration of cardiac involvement in patients was 8.6 years with SD=6.26. In AS group, 48 (96%) patients suffered from back pain, 43 from enteritis, 100% from Ankylosing Spondylitis, one from unilateral involvement, 22(44%) from peripheral arthritis and 27 (54%) from HLA-B27. CONCLUSION: In total, Average heart involvement in the control group and AS group was 13.25 with SD=7.64 and 16.2 with SA=8.54, respectively, indicating no significant difference. In sum, based on the results obtained in this study, some types of heart involvements, such as mitral valve regurgitation and Mitral Valve Prolapse in AS patients are more prevalent than in the normal population.