Musculoskeletal complaints and its economic impact in an Iranian army hospital.

AIM: Musculoskeletal conditions constitute a remarkable portion of disability cases in the military. This study evaluated the distribution and types of musculoskeletal problems and estimated the direct and indirect costs due to these complaints in an Iranian military hospital. METHODS: All medical records of patients with musculoskeletal complaints that were referred to the medical committee of a military hospital, including rheumatology, orthopedics, and neuro-surgical specialists, from 2014 to 2016, were reviewed. Details of each complaint and the final opinion of the medical committees were recorded. The cost of each diagnostic step was calculated based on the recorded data. The treatment costs were estimated for each complaint by calculating the average cost of treatment plans suggested by two specialists, a physical medicine and a rheumatologist. The estimated cost for each part is calculated based on the army insurance low. Indirect costs due to absences, inability to work, and disability were assessed and added to the above-mentioned direct costs. Statistical analysis was performed using SPSS version 21. RESULTS: 2,116 medical records of the committee were reviewed. 1252 (59.16%) cases were soldiers (who had to spend two years of mandatory duty in the army), and 864 (40.83%) cases were non-soldiers. The three most common complaints were fractures (301 cases, 14.22%), low back pain due to lumbar disc bulges and herniations (303 cases, 14.31%), and genu varus/genu valgus (257 cases, 12.14%). The most affected sites were the lower limbs and vertebral column. According to an official document in these subjects' records, 4120 person-days absent from work were estimated annually, and nearly $1,172,149 of annual economic impact was calculated. CONCLUSION: Musculoskeletal problems are common in the army, and establishing preventive strategies for these conditions is essential. The conservative and medical approach and the proper education for correct movement and the situation should be mentioned for the reduction of disability and its economic burden on the army's staff.

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.

Synovial biopsy for establishing a definite diagnosis in undifferentiated chronic knee monoarthritis.

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.

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.

2018 APLAR axial spondyloarthritis treatment recommendations.

INTRODUCTION: Despite the availability of axial spondyloarthritis (SpA) recommendations proposed by various rheumatology societies, we considered that a region-specific guideline was of substantial added value to clinicians of the Asia-Pacific region, given the wide variations in predisposition to infections and other patient factors, local practice patterns, and access to treatment across countries. MATERIALS AND METHODS: Systematic reviews were undertaken of English-language articles published between 2000 and 2016, identified from MEDLINE using PubMed, EMBASE and Cochrane databases. The strength of available evidence was graded using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach. Recommendations were developed through consensus using the Delphi technique. RESULTS: Fourteen axial SpA treatment recommendations were developed based on evidence summaries and consensus. The first 2 recommendations cover non-pharmacological approaches to management. Recommendations 3 to 5 describe the following: the use of non-steroidal anti-inflammatory drugs as first-line symptomatic treatment; the avoidance of long-term corticosteroid use; and the utility of conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) for peripheral or extra-articular manifestations. Recommendation 6 refers to the indications for biological DMARDs (bDMARDs). Recommendation 7 deals specifically with screening for infections endemic to Asia, prior to use of bDMARDs. Recommendations 7 to 13 cover the role of bDMARDs in the treatment of active axial SpA and include related issues such as continuing therapy and use in special populations. Recommendation 14 deals with the utility of surgical intervention in axial SpA. CONCLUSION: These recommendations provide up-to-date guidance for treatment of axial SpA to help meet the needs of patients and clinicians in the Asia-Pacific region.

2018 APLAR axial spondyloarthritis treatment recommendations

Despite the availability of axial spondyloarthritis (SpA) recommendations proposed by various rheumatology societies, we considered that a region-specific guideline was of substantial added value to clinicians of the Asia-Pacific region, given the wide variations in predisposition to infections and other patient factors, local practice patterns, and access to treatment across countries.Systematic reviews were undertaken of English-language articles published between 2000 and 2016, identified from MEDLINE using PubMed, EMBASE and Cochrane databases. The strength of available evidence was graded using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach. Recommendations were developed through consensus using the Delphi technique.Fourteen axial SpA treatment recommendations were developed based on evidence summaries and consensus. The first 2 recommendations cover non-pharmacological approaches to management. Recommendations 3 to 5 describe the following: the use of non-steroidal anti-inflammatory drugs as first-line symptomatic treatment; the avoidance of long-term corticosteroid use; and the utility of conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) for peripheral or extra-articular manifestations. Recommendation 6 refers to the indications for biological DMARDs (bDMARDs). Recommendation 7 deals specifically with screening for infections endemic to Asia, prior to use of bDMARDs. Recommendations 7 to 13 cover the role of bDMARDs in the treatment of active axial SpA and include related issues such as continuing therapy and use in special populations. Recommendation 14 deals with the utility of surgical intervention in axial SpA.These recommendations provide up-to-date guidance for treatment of axial SpA to help meet the needs of patients and clinicians in the Asia-Pacific region.

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.

Performance of the 2010 Rheumatoid Arthritis Classification Criteria.

OBJECTIVES: Rheumatoid arthritis (RA) needs early treatment to improve clinical outcome by reducing joint damage, radiographic progression and disability. The aim of this study was to evaluate the 2010 Rheumatoid Arthritis Classification Criteria for its ability to classify RA patients, in their early stages, not exceeding 12 months of disease progression. METHODS: Rheumatoid arthritis (RA) patients were selected from August to December 2010, among those coming for their follow-up. The inclusion criteria were patients with not more than 12 months of disease progression at their first evaluation. Patients were selected from four rheumatology subspecialty clinics. RESULTS: Nine hundred and ninety-seven patients with a confirmed diagnosis of RA entered the study. The female-to-male ratio was 4.3/1.0. Mean age was 46.4 years. Mean disease progression at first visit was 6.3 months. The mean follow-up of their disease was 5.9 years. The 1987 American College of Rheumatology (ACR) criteria were fulfilled for 74% of patients. The ACR/EULAR (European League Against Rheumatism) criteria were fulfilled for 69% of patients. Ten percent had involvement of 2-10 large joints, 29% 1-3 small joints, 25% 4-10 small joints and 32% more than 10 joints. Low rheumatoid factor (RF)/anticytoplasmic antibodies (ACPA) were discovered in 30%, high RF/ACPA in 37%; high erythrocyte sedimentation rate/C-reactive protein in 77%, and duration of 6 weeks or more in 92% of patients. There was no significant difference between men and women. CONCLUSIONS: The 2010 ACR/EULAR criteria have good performance: sensitivity of 69% in early disease (first year), with the same sensitivity in both genders.