Risk of Total Knee and Hip Arthroplasty in Patients With Rheumatoid Arthritis: A 12-Year Retrospective Cohort Study of 65,898 Patients.

BACKGROUND: Rheumatoid arthritis (RA) is an inflammatory disease that causes the destruction of soft tissues and cartilage around joints. Owing to the widespread use of potent disease-modifying antirheumatic drugs, the need for total knee and hip arthroplasties (TKA and THA) has been reduced in patients with RA. However, the current association between RA and either THA or TKA has not been demonstrated in large-scale epidemiological studies. METHODS: We conducted a large-scale retrospective cohort study of patients diagnosed with RA during a 12-year period (2000-2012) in Taiwan. We recruited 32,949 patients with RA and 32,949 individually propensity score-matched non-RA controls. RESULTS: After adjusting for confounding factors, we found that the risk of THA or TKA was 4.02 times higher in patients with RA than in those without RA (95% confidence interval [CI], 3.77-4.52). The risk of THA or TKA was highest in patients with RA younger than 40 years (adjusted hazard ratio, 43.18; 95% CI, 16.01-116.47). Compared with non-RA patients, patients with RA were 4.82 times more likely to undergo THA (95% CI, 3.84-6.04), 3.85 times more likely to undergo TKA (95% CI, 3.48-4.25), and 19.06 times more likely to undergo both THA and TKA (95% CI, 8.90-40.80). CONCLUSION: These findings document a 4.02-fold greater long-term risk of undergoing THA or TKA in RA patients relative to non-RA patients in Taiwan.

Patient-tailored dose reduction of tumor necrosis factor inhibitors in axial spondyloarthritis.

Tumor necrosis factor inhibitors have been widely used in the field of axial spondyloarthritis, with current guidelines now recommending dose reduction instead of withdrawal of biologics. Systemic review and meta-analyses in literature have summarized present tapering strategies and principles in published heterogeneous studies. In this study, we reviewed and provided an update on present evidence based on prospective and retrospective studies from 2008 to 2022 by performing a literature review of related publications on remission or relapse from PubMed. We further stated the core issues concerning dose reduction, including the timing, optimization, intensity, maintenance, monitoring, factors associated with tapering and solutions to de-escalation failure. Remission/relapse should be the principal consideration in dose reduction implementation for individuals without comorbidities. As a treat-to-target scope of this multifaceted systemic disease, extra-articular manifestations such as uveitis, psoriasis, inflammatory bowel disease, cardiovascular complication, hip involvement and progressed structural damage influence patient-tailored dose reduction plans. Safety concerns and costs should be integrated into the decision-making schedule to optimize the individualized dose reduction paradigm.

Association of Hallux Valgus with Degenerative Spinal Diseases: A Population-Based Cohort Study.

Background: Although hallux valgus is known to cause lower-back pain, the association between hallux valgus and spinal degenerative disease remains unclear. Methods: A retrospective cohort study was conducted between 1 January 2000 and 31 December 2015 using data from the Longitudinal Health Insurance Database in Taiwan. After propensity score matching for age, sex, and some potential comorbidities, 1000 individuals newly diagnosed with hallux valgus were enrolled in the study group, while 1000 individuals never diagnosed with hallux valgus served as the control group. Both groups were followed up until 2015 to evaluate the incidence of hallux valgus. Kaplan-Meier analysis was used to determine the cumulative incidence of hallux valgus, while the Cox proportional hazard model was adopted to estimate the hazard ratio (HR) and adjusted hazard ratio (aHR) with 95% confidence intervals (CIs). Results: The incidence densities of spinal degeneration in the hallux valgus and non-hallux valgus groups were 73.10 and 42.63 per 1000 person-years, respectively. An increased risk of spinal degenerative changes was associated with hallux valgus (adjusted HR = 1.75, 95% CI = 1.50−2.05). Age- and sex-stratified analyses showed a significantly higher risk of spinal degeneration in the hallux valgus group. Moreover, sub-outcome evaluations revealed significantly higher risks of spondylosis (aHR = 2.01, 95% CI = 1.55−2.61), intervertebral disorder (aHR = 2.27, 95% CI = 1.62−3.17), and spinal stenosis (aHR = 1.24, 95% CI = 1.47−1.76). There was also an increased risk of spinal degenerative change in those with hallux valgus without surgical intervention (aHR = 1.95, 95% CI = 1.66−2.99, p < 0.001). Conclusions: Hallux valgus was associated with increased risk of degenerative spinal changes and other spinal disorders.

Recent targets of osteoarthritis research.

Osteoarthritis is one of the most common diseases and poses a significant medical burden worldwide. Currently, the diagnosis and treatment of osteoarthritis primarily rely on clinical symptoms and changes observed in radiographs or other image modalities. However, identification based on reliable biomarkers would greatly improve early diagnosis, help with precise monitoring of disease progression, and provide aid for accurate treatment. In recent years, several biomarkers for osteoarthritis have been identified, including image modalities and biochemical biomarkers such as collagen degradation products, pro- or anti-inflammatory cytokines, micro RNAs, long non-coding RNAs, and circular RNAs. These biomarkers offer new insights in the pathogenesis of osteoarthritis and provide potential targets for further research. This article reviews the evolution of osteoarthritis biomarkers from the perspective of pathogenesis and emphasizes the importance of continued research to improve the diagnosis, treatment, and management of osteoarthritis.

Benefits of tumor necrosis factor inhibitors for cardiovascular disease in ankylosing spondylitis.

Ankylosing spondylitis (AS) has been associated with an increased cardiovascular disease (CVD) risk, with current guidelines recommending multiple CVD-related risk assessment strategies. CVD risk prediction using a scoring model with lipids might be another promising alternative, for which ultrasound screening for subclinical atherosclerosis may be considered together with surrogate markers. Theoretically, tumor necrosis factor inhibitors (TNFi), which are known to inhibit endothelial activation and inflammation caused by the disease and underlying metabolic dysfunction, might prevent microvascular events. In this narrative review, we summarized the evidence of TNFi effects on CVD in AS. Although early case reports revealed that CVD occurred during TNFi treatment, more recent evidence shows that it could be successfully treated. Studies of TNFi on lipid changes and subclinical atherosclerosis have shown controversial results, possibly due to genetic predisposition, differences in affinity for membrane-bound TNF leading to insufficient inhibition of inflammation or primary failure response to TNFi, and not enough follow-up time to identify potential significance. Overall, patients vulnerable to CVD could benefit from long-term administration of TNFi when inflammation is under control. Besides healthy lifestyle modification, traditional CVD risk factors and metabolic syndrome-related diseases should be further assessed and treated if necessary.

No increased risk of alopecia in ankylosing spondylitis patients: A population-based cohort study in Taiwan.

AIM: To investigate the association between ankylosing spondylitis (AS) and alopecia. METHODS: In this cohort study, data from over 1 000 000 patients in the Taiwan Longitudinal Health Insurance Database were extracted. We selected newly diagnosed (outpatient department visit three or more times or admission at least once) patients with AS (ICD-9-CM = 720.0) from 2000 to 2012. For the non-AS comparison group, patients never diagnosed with AS were chosen from 1999 to 2013. In all, 3640 AS patients and 14 560 non-AS controls were selected. Cox proportional hazard model and Kaplan-Meier analysis were used to present the results. The adjusted hazard ratio (HR) in the Cox proportional hazard model was adjusted for age, sex, hypertension, hyperlipidemia, diabetes, atopic dermatitis, and mental disorder. RESULTS: No increased risk of alopecia in AS patients was shown in the Cox proportional hazard model (crude HR 1.16, P = 0.595; adjusted HR 1.16, P = 0.599). Negative results are found as well in subgroup analysis of different age, sex (age 20-40 y: HR 1.03, P = 0.925; Age ≥40 y: HR 1.49, P = 0.406; Female: HR 1.17, P = 0.759; Male: HR 1.15, P = 0.667), and phenotypes of alopecia (androgenetic alopecia: HR 1.19, 95% confidence interval [CI] 0.58-2.41; alopecia areata: HR 0.98, 95% CI 0.37-2.62). A significant positive correlation is found between atopic dermatitis and alopecia (adjusted HR 8.05, P = 0.039). CONCLUSION: In this population-based cohort study, we found no association of risk of alopecia and AS.

Celecoxib and Etoricoxib may reduce risk of ischemic stroke in patients with rheumatoid arthritis: A nationwide retrospective cohort study.

Background and purpose: Previous studies reported conflicting results about the risk of ischemic stroke associated with the use of non-steroidal anti-inflammatory drugs (NSAIDs) in patients with rheumatoid arthritis (RA). We aimed to investigate two specific COX-2 inhibitors, Celecoxib and Etoricoxib, and their corresponding effects on the risk of ischemic stroke in patients with RA. Patients and methods: 10,857 patients newly diagnosed with RA were identified and sampled from the Taiwanese National Health Insurance Research Database during the period from 2001 to 2009. The identification of RA was based on the criteria of ICD-9-CM diagnosis code 714.0. Patients diagnosed with cerebrovascular disease and those receiving RA treatment prior to the first diagnosis of RA were excluded. Study endpoint was ischemic stroke, defined by ICD-9-CM code. Cox proportional hazard models and Kaplan Meier curves were used to reveal covariates and differences by drugs in the risk of ischemic stroke. Dosages for Celecoxib were defined as ≤ 200 and >200 mg/day; those for Etoricoxib were 0 and >0 mg/day. Results: Among 7,904 RA patients, 6,669 did not take Celecoxib and 564 (8.46%) of them experienced an ischemic stroke event. Of the 597 individuals who took ≤ 200 mg/day of Celecoxib, 58 (9.72%) had strokes. Of the 638 patients who took >200 mg/day of Celecoxib, 38 (5.96%) eventually experienced a stroke. Among the 7,681 patients who did not take Etoricoxib, 654 (8.51%) experienced an ischemic stroke, while 6 (2.69%) in 223 patients who consumed Etoricoxib had a stroke event. Consuming more than 200 mg of Celecoxib per day for <3.5 years lowered the incidence rate for strokes [hazard ratio (HR) 0.67, 95% Confidence Interval (CI) 0.48-0.93 for dosage and HR 0.22, 95% CI 0.10-0.46 for duration, both p < 0.001], while consuming any dosage of Etoricoxib significantly decreases the possibility (HR 0.35, 95% CI 0.16-0.80, p < 0.001). On the other hand, consuming Etoricoxib for 8 years might have a neutral or even a potentially protective effect compared to at 3.8 years. Conclusion: This population-based retrospective cohort study has shown that Celecoxib and Etoricoxib reduce the risk of ischemic stroke in patients with RA in a dose- and time-dependent manner.

Patients With Ankylosing Spondylitis Are Associated With High Risk of Fibromyalgia: A Nationwide Population-Based Cohort Study.

Objectives: The main purpose of this retrospective cohort study was to provide an evaluation of Ankylosing spondylitis (AS) patients' fibromyalgia risk in different age and sex subgroups by analyzing large study samples. Methods: Datasets from the National Taiwan Insurance Research Database (NHIRD) were retrieved in this retrospective cohort study. This study was approved by the Institutional Review Board of Chung Shan Medical University (IRB permit number CS15134). Within the Longitudinal Health Insurance Database (LHID), and the subset of NHIRD, we identified AS patients to explore the risk of further fibromyalgia. The exposure cohort included patients with newly-diagnosed AS (ICD-9-CM:720.0) during 2000-2013. After 1:4 age-sex matching and 1:2 propensity score matching, and adjusting potential confounders, individuals without AS were identified as a comparison cohort. The adjusted hazard ratio of subsequent development of fibromyalgia in people with AS was evaluated. Further stratification analyses of different ages and genders were then undertaken to validate the results. Results: In total, 17 088 individuals were included in the present study, including 5,696 patients with AS and 11,392 individuals without AS. Respective incidence rates (per 1,000 person-months) of fibromyalgia was 0.52 (95% CI, 0.46-0.59) in the AS cohort and 0.39 (95% CI, 0.35-0.44) in the non-AS cohort. Compared with the non-AS cohort, aHR of developing fibromyalgia was 1.32 (95% CI, 1.12-1.55) in people with AS. This association was consistent in both statistical models of 1:4 age-sex matching and 1:2 propensity score matching. Conclusion: Patients with AS were associated with a higher risk of fibromyalgia, especially those over 65 years old. In managing patients with AS, clinicians should be aware of this association, which could impact diagnosis, disease activity evaluation, and treatment.

Opposing Trends in Total Knee and Hip Arthroplasties for Patients With Rheumatoid Arthritis vs. the General Population-A 14-Year Retrospective Study in Taiwan.

Objective: To determine the trend of incidence rate of total knee arthroplasty (TKA), total hip arthroplasty (THA), and TKA or THA (major joint arthroplasty, MJA) among rheumatoid arthritis (RA) population and compared them with general population (GP) in Taiwan. Methods: Incidence rates and trends of TKA, THA, and MJA were determined over a 14-year period (2000-2013) among RA patients and compared them with GP. RA of patients was diagnosed based on the ACR 1987 criteria and extracted from GP. Subanalyses of incidences of TKA, THA, and MJA by year, 10-year age group, and gender were further conducted for demographic analysis. Patient profiles were extracted from the National Health Insurance Research Database (NHIRD) for interrupted time-series analysis and cohort studies. Results: Patients enrolled were 168,457 receiving TKA, 64,543 receiving THA, and 228,191 receiving MJA surgery. Incidences of TKA, THA, and MJA in RA patients were significantly lower by 49.0, 41.5, and 41.0% compared with concomitantly rises in GP by 131.0, 25.1, and 90.0% among the GP during the study period. The dominant age population for TKA, THA, and MJA were those aged 70-79 years in both GP and RA groups. Conclusions: We found an opposing trend in incidence of TKA, THA, and MJA between RA patients and the GP. The possible influence of pharmacological treatment is implicated for the lower incidence rates of TKA, THA, and MJA surgeries among RA patients.

Ixekizumab for the treatment of ankylosing spondylitis.

INTRODUCTION: Ixekizumab (IXE) is a high affinity IgG4 approved for the treatment of ankylosing spondylitis (AS). Recently, two phase III randomized clinical trials (COAST-V, COAST-W) showed significant and sustained improvements in signs and symptoms of AS as evaluated by ASAS40 response. Areas covered: The authors performed a comprehensive literature search on this topic, by a review of published articles to date. The authors introduced the structure and the mechanism of action of IXE, and critically reviewed data from clinical trials, concerning its efficacy and safety in AS.Expert opinion: IXE proved dramatic efficacy and tolerable safety in patients with AS, in particular, patients with intolerance or insufficient response to TNFi, which provides an alternative and breakthrough for the treatment options of AS. IXE might not work in AS with IBD and uveitis involvement. Patients treated with IXE should be aware of candida infection in long term application.

Impact of Rheumatoid Arthritis on Alopecia: A Nationwide Population-Based Cohort Study in Taiwan.

Objectives: Studies on the relationship between rheumatoid arthritis (RA) and alopecia areata (AA) are limited. This study investigated the effect of RA on alopecia areata risk in a nationwide cohort study. Methods: We analyzed 2000-2012 data from the Longitudinal Health Insurance Database in Taiwan. The follow-up period was extended up to the end of 2013. We defined RA as a diagnosis using International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) code 714.0 during at least three outpatient visits or one admission and the use of disease-modifying antirheumatic drugs (DMARDs) for >30 days. The enrollees with AA were identified using the ICD-9-CM code 704.01. We enrolled a comparison cohort comprising participants randomly matched by age and sex, with the same index date as that of the study cohort. Furthermore, we investigated alopecia risk by using Cox proportional-hazards regression models after propensity score matching for sex, age, comorbidities, and medication use. Results: In total, 2,905 patients with RA (74% women, mean age: 51.9 years) and 2,905 controls were followed for 22,276 and 25,732 person-years, respectively. Alopecia risk was 2.64-fold (95% confidence interval = 1.47-4.76) higher in patients with RA than in patients without RA after age, sex, comorbidities, and medication use were adjusted for. In addition, patients with thyroid disease presented considerable alopecia risk. Patients with RA in the younger age group (20-40 years) had the highest alopecia risk. Conclusions: Alopecia risk is significantly higher in patients with RA than in those without RA, particularly in the younger age group (20-40 years). RA assessment should be considered when examining patients with alopecia, especially young adults.

The effect of pay for performance on risk incidence of hip fracture in type 2 diabetic patients: a nationwide population-based cohort study.

OBJECTIVES: Diabetes mellitus (DM) increases the risk of hip fracture. The literature rarely discusses the importance of pay-for-performance (P4P) programs for the incidence of hip fractures in patients with type 2 DM (T2DM). This study aimed to examine the impact of the P4P program on hip fracture risk in patients with T2DM. METHODS: This retrospective cohort study focused on data from T2DM patients aged 45 and older between 2001 and 2012. We continued to track these data until 2013. The data were collected from the National Health Insurance Research Database in Taiwan. To minimize selection bias, T2DM patients were divided into P4P enrollees and non-enrollees. Propensity score matching by greedy matching technique (1:1 ratio) was used to include 252,266 participants. A Cox proportional hazard model was performed to examine the impact of the P4P program on hip fracture risk. We used the bootstrap method to perform sensitivity analysis by random sampling with replacement. RESULTS: Our results showed that the risk of hip fracture in P4P enrollees was 0.92 times that of non-enrollees. (hazards ratio [HR] = 0.92; 95% confidence interval [CI]: 0.85-0.99). P4P enrollees who received regular treatment had lower risk in the first 4 years (HR = 0.90; 95%CI: 0.84-0.96) but no statistically significant difference after 4-year enrollment (HR = 0.99; 95%CI: 0.93-1.06). There was no statistically significant difference in the effect of hip fractures between P4P non-enrollees and P4P enrollees with irregular treatment (HR = 0.94, 95%CI: 0.87-1.03). Through sensitivity analysis, the results also showed P4P enrollees had a lower risk of hip fracture compared to P4P non-enrollees (mean HR = 0.919; 95% CI: 0.912-0.926). Stratified analysis showed that patients without DM complications (DCSI = 0) who enrolled in P4P had lower risks of hip fractures than the non-enrollees (HR = 0.90; 95% CI: 0.82-0.98). CONCLUSION: T2DM patients enrolled in P4P program can reduce the risks of hip fracture incidence. Early inclusion of patients without DM complications in the P4P program can effectively reduce hip fractures.

Patients With Rheumatoid Arthritis Increased Risk of Developing Osteoarthritis: A Nationwide Population-Based Cohort Study in Taiwan.

Objective: To investigate the risk of developing OA in patients diagnosed with RA. Methods: In this study, we presented gender, age, urbanization, occupation and, comorbidities in a RA cohort and a non-RA cohort based on number and percentage. We investigated the OA risk in patients with RA. We conducted a retrospective cohort study with a 13-year longitudinal follow-up in Taiwan. Patients who received RA diagnoses between 2000 and 2012 were enrolled in the study cohort. The non-RA cohort were 1:1 propensity score matched with the RA cohort by age, gender, index year, urbanization, occupation, and comorbidities. The hazard ratios (HRs) and adjusted HRs (aHRs) were estimated after confounders were adjusted. Sensitivity analysis utilizing the Longitudinal Health Insurance Database (LHID) was conducted. Results: We totally enrolled 63,626 cases in RA patients (study cohort) and matched controls. In the RA cohort, the crude HR for OA was 2.86 (95% confidence interval (CI), 2.63-3.11, p < 0.001), and the aHR was 2.75 (95% CI, 2.52-2.99, p < 0.001). (The study demonstrated that patients with RA had a higher risk for developing OA compared with the non-RA controls. Conclusion: Developing effective OA prevention strategies are necessary in patients with RA. This finding may be extended to evaluate the risk of OA among other kinds of inflammatory autoimmune diseases. Identifying the key pathogenesis mechanisms are necessary in the future study.