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). 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. 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. 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. IRCT.ir, IRCT2015030321315N1 . Registered on 5 April 2015.

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.

Background: Undifferentiated arthritis is a condition in which the problem cannot be classified into any definite diagnosis category. Various methods have been suggested to clarify the definite diagnosis in this class. The synovial biopsy is suggested as the last diagnostic approach to determine the precise histopathological diagnosis. In this study, we aimed to evaluate the efficacy of synovial biopsy for establishing a definite diagnosis in patients with undifferentiated chronic knee monoarthritis.Methods: The present retrospective case series was conducted in 2005 in the rheumatology research center of Shariati hospital and the 501 hospital in Tehran, Iran. The study included the synovial biopsy of patients with chronic knee monoarthritis who did not have a definite diagnosis after all the diagnostic steps before the synovial biopsy. Pathology slides of the patients’ synovial biopsy were reevaluated with a senior expert pathologist.Results: Eighty patients with a mean age of 37.6 ± 17.32 years (range: 6–68) were included, of whom 50% were female. The gap time between the onset of knee monoarthritis and the decision-making for synovial biopsy was 14.34 ± 19.61 months. Histopathologic evaluations revealed non-specific synovitis in 65% of the patients and a definite diagnosis in 35%. The most common definite diagnosis was rheumatoid arthritis (9%), followed by septic arthritis (5%). The most common pathologic findings were endothelial proliferation (89%) and synovial proliferation (88%), and the most common infiltrating cell was lymphocyte (54%). Patients with non-specific synovitis were more likely to have neovascularization, cellular infiltration (p-value < 0.001), synovial proliferation, endothelial proliferation (p-value = 0.001), pannus formation (p-value = 0.009), and fibrosis (p-value = 0.022) compared to the patients with a definite pathologic diagnosis. However, age, gender, and the gap time between disease symptoms to synovial biopsy were not significantly different between the different groups of diagnosis (p-value > 0.05).Conclusion: Non-specific synovitis remains the most common histopathologic finding, highlighting the importance of physician expert opinion for most of the patients with undifferentiated chronic knee monoarthritis. Studies with larger samples and immunohistochemistry analyses are needed to clarify this uncategorized entity further.

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. 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. 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). 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.

Background: Undifferentiated arthritis is a condition in which the problem cannot be classified into any definite diagnosis category. Various methods have been suggested to clarify the definite diagnosis in this class. The synovial biopsy is suggested as the last diagnostic approach to determine the exact histopathological diagnosis. In this study, we aimed to evaluate the efficacy of synovial biopsy for establishing a definite diagnosis in patients with undifferentiated chronic knee monoarthritis. Methods: The present retrospective case series was conducted in 2005 in the rheumatology research center of Shariati hospital and the 501 hospital in Tehran, Iran. The study included the synovial biopsy of patients with chronic knee monoarthritis who did not have a definite diagnosis after all the diagnostic steps before the synovial biopsy. Pathology slides of the patients’ synovial biopsy were reevaluated with a senior expert pathologist. Results: Eighty patients with a mean age of 37.6 ± 17.32 years (range: 6 – 68) were included, of whom 50% were female. The gap time between the onset of knee monoarthritis and the decision-making for synovial biopsy was 14.34 ± 19.61 months. Histopathologic evaluations revealed non-specific changes in 65% of the patients and a definite diagnosis in 35%. The most common definite diagnosis was rheumatoid arthritis (9%), followed by septic arthritis (5%). The most common pathologic findings were endothelial proliferation (89%) and synovial proliferation (88%), and the most common infiltrating cell was lymphocyte (54%). Patients with non-specific changes were more likely to have neovascularization, cellular infiltration (p-value < 0.001), synovial proliferation, endothelial proliferation (p-value = 0.001), pannus formation (p-value = 0.009), and fibrosis (p-value = 0.022) compared to the patients with a definite pathologic diagnosis. However, age, gender, and the gap time between disease symptoms to synovial biopsy were not significantly different between the different groups of diagnosis (p-value > 0.05). Conclusions: Non-specific changes remain the most common histopathologic finding, highlighting the importance of physician expert opinion for most of the patients with undifferentiated chronic knee monoarthritis. Studies with larger samples and immunohistochemistry analyses are needed to clarify this uncategorized entity further.