Evaluating the potential of Vitamin D and curcumin to alleviate inflammation and mitigate the progression of osteoarthritis through their effects on human chondrocytes: A proof-of-concept investigation.

Osteoarthritis (OA) is a chronic degenerative joint disorder primarily affecting the elderly, characterized by a prominent inflammatory component. The long-term side effects associated with current therapeutic approaches necessitate the development of safer and more efficacious alternatives. Nutraceuticals, such as Vitamin D and curcumin, present promising therapeutic potentials due to their safety, efficacy, and cost-effectiveness. In this study, we utilized a proinflammatory human chondrocyte model of OA to assess the anti-inflammatory properties of Vitamin D and curcumin, with a particular focus on the Protease-Activated Receptor-2 (PAR-2) mediated inflammatory pathway. Employing a robust siRNA approach, we effectively modulated the expression of PAR-2 to understand its role in the inflammatory process. Our results reveal that both Vitamin D and curcumin attenuate the expression of PAR-2, leading to a reduction in the downstream proinflammatory cytokines, such as Tumor Necrosis Factor-alpha (TNF-α), Interleukin 6 (IL-6), and Interleukin 8 (IL-8), implicated in the OA pathogenesis. Concurrently, these compounds suppressed the expression of Receptor Activator of Nuclear Factor kappa-Β Ligand (RANKL) and its receptor RANK, which are associated with PAR-2 mediated TNF-α stimulation. Additionally, Vitamin D and curcumin downregulated the expression of Interferon gamma (IFN-γ), known to elevate RANKL levels, underscoring their potential therapeutic implications in OA. This study, for the first time, provides evidence of the mitigating effect of Vitamin D and curcumin on PAR-2 mediated inflammation, employing an siRNA approach in OA. Thus, our findings pave the way for future research and the development of novel, safer, and more effective therapeutic strategies for managing OA.

Efficient Generation of Chondrocytes From Bone Marrow-Derived Mesenchymal Stem Cells in a 3D Culture System: Protocol for a Practical Model for Assessing Anti-Inflammatory Therapies.

BACKGROUND: Chondrocytes are the primary cells responsible for maintaining cartilage integrity and function. Their role in cartilage homeostasis and response to inflammation is crucial for understanding the progression and potential therapeutic interventions for various cartilage-related disorders. Developing an accessible and cost-effective model to generate viable chondrocytes and to assess their response to different bioactive compounds can significantly advance our knowledge of cartilage biology and contribute to the discovery of novel therapeutic approaches. OBJECTIVE: We developed a novel, streamlined protocol for generating chondrocytes from bone marrow-derived mesenchymal stem cells (BMSCs) in a 3D culture system that offers significant implications for the study of cartilage biology and the discovery of potential therapeutic interventions for cartilage-related and associated disorders. METHODS: We developed a streamlined protocol for generating chondrocytes from BMSCs in a 3D culture system using an "in-tube" culture approach. This simple pellet-based 3D culture system allows for cell aggregation and spheroid formation, facilitating cell-cell and cell-extracellular matrix interactions that better mimic the in vivo cellular environment compared with 2D monolayer cultures. A proinflammatory chondrocyte model was created by treating the chondrocytes with lipopolysaccharide and was subsequently used to evaluate the anti-inflammatory effects of vitamin D, curcumin, and resveratrol. RESULTS: The established protocol successfully generated a large quantity of viable chondrocytes, characterized by alcian blue and toluidine blue staining, and demonstrated versatility in assessing the anti-inflammatory effects of various bioactive compounds. The chondrocytes exhibited reduced inflammation, as evidenced by the decreased tumor necrosis factor-α levels, in response to vitamin D, curcumin, and resveratrol treatment. CONCLUSIONS: Our novel protocol offers an accessible and cost-effective approach for generating chondrocytes from BMSCs and for evaluating potential therapeutic leads in the context of inflammatory chondrocyte-related diseases. Although our approach has several advantages, further investigation is required to address its limitations, such as the potential differences between chondrocytes generated using our protocol and those derived from other established methods, and to refine the model for broader applicability and clinical translation.

Reconnoitering the Therapeutic Role of Curcumin in Disease Prevention and Treatment: Lessons Learnt and Future Directions.

Turmeric is a plant with a very long history of medicinal use across different cultures. Curcumin is the active part of turmeric, which has exhibited various beneficial physiological and pharmacological effects. This review aims to critically appraise the corpus of literature associated with the above pharmacological properties of curcumin, with a specific focus on antioxidant, anti-inflammatory, anticancer and antimicrobial properties. We have also reviewed the different extraction strategies currently in practice, highlighting the strengths and drawbacks of each technique. Further, our review also summarizes the clinical trials that have been conducted with curcumin, which will allow the reader to get a quick insight into the disease/patient population of interest with the outcome that was investigated. Lastly, we have also highlighted the research areas that need to be further scrutinized to better grasp curcumin's beneficial physiological and medicinal properties, which can then be translated to facilitate the design of better bioactive therapeutic leads.

Increased risk of brain metastases in ovarian cancer patients with BRCA mutations.

PURPOSE: To estimate the risk for brain metastases in patients with ovarian cancer using real-world data, and assess whether BRCA mutations increase that risk. METHODS: This retrospective study included 4515 patients diagnosed with ovarian cancer between January 1, 2011, and January 31, 2018, from the Flatiron Health database, a longitudinal, demographically, and geographically diverse database derived from electronic health records in the United States. RESULTS: Forty-six (1%) patients were diagnosed with brain metastases after being diagnosed with ovarian cancer. Of 4515 patients with ovarian cancer, 10% had a known BRCA mutation, 37% had BRCA wildtype (BRCAwt), and the BRCA status of the remaining 51% was unknown/untested. Brain metastases were observed in 3% of patients with BRCA mutations compared with 0.6% of those with BRCAwt. The Kaplan-Meier estimate for the proportion of patients with brain metastases within 5 years of diagnosis was 5.7% in the population with BRCA mutations compared with 1.4% in those with BRCAwt (hazard ratio 4.44; 95% confidence interval, 1.97, 10.00; P < 0.0001). These data demonstrate that patients with a BRCA mutation had a significantly higher risk for brain metastases than those without. CONCLUSION: Despite being a rare manifestation of ovarian cancer, the possibility of developing brain metastases should be considered in these patients, especially in patients with a BRCA mutation. The availability of new therapeutic options that may prolong overall survival and may not cross the blood-brain barrier could also lead to an increase in brain metastases in patients with ovarian cancer.

Outcomes and healthcare resource utilization associated with medically attended hypoglycemia in older patients with type 2 diabetes initiating basal insulin in a US managed care setting.

OBJECTIVE: To assess health outcomes and the economic burden of hypoglycemia in older patients with type 2 diabetes initiating basal insulin (BI). RESEARCH DESIGN AND METHODS: Medicare Advantage claims data were extracted for patients with type 2 diabetes initiating BI and patients were stratified into two groups: those with medically attended hypoglycemia during the first year of BI treatment (HG group) and those without (non-HG group). Main outcome measures were hospitalization, mortality, healthcare utilization and costs 1 year before and 1 year after BI initiation. RESULTS: Of 31,035 patients included (mean age 72 years [SD 9.2]), 3066 (9.9%; HG group) experienced hypoglycemia during 1 year post-BI initiation. After adjustment for demographic, comorbidity and medication history, hypoglycemia was associated with risk of hospitalization (HR 1.59; 95% CI: 1.53-1.65) and death (HR 1.50; 95% CI: 1.40-1.60). Healthcare utilization was higher pre-index and showed greater increases post-BI initiation in the HG vs. the non-HG group. Per-patient healthcare costs were substantially higher for the HG group than the non-HG group, both pre-index ($54,057 vs. $30,249, respectively) and post-BI initiation ($75,398 vs. $27,753, respectively). CONCLUSIONS: Based on available claims data, hypoglycemia during the first year of BI treatment is associated with risk of hospitalization or death in older people, increasing healthcare utilization and costs. Due to the observational nature of this study, causality cannot be attributed, and further prospective studies into the effect of hypoglycemia on health outcomes in this population are warranted.

The peculiar economics of life-extending therapies: a review of costing methods in health economic evaluations in oncology.

Published literature lacks consensus, and most guidelines lack definitive recommendations as to whether cost-effectiveness analyses (CEAs) should include all "future" costs or distinguish between related and unrelated medical costs. This systematic review of oncology CEAs evaluated cost methods used and the impact on the cost-effectiveness of incorporating different cost categories, including costs due to study intervention, related medical costs of the treated condition, and unrelated medical costs. Of the 59 studies reviewed, none included medical costs unrelated to the treated condition and 14 studies (32%) excluded direct medical costs related to the condition but not the evaluated intervention. Recomputing ICERs using different cost categories altered overall cost-effectiveness conclusions. The authors propose conventional CEA methods may implicitly penalize therapies that add "expensive" life years for chronically ill patients. Presenting ICERs computed with and without disease-attributable costs can help better convey how much the treatment itself contributes to overall costs.

Effects of clinical use and sterilization on surface topography and surface roughness of three commonly used types of orthodontic archwires.

AIM: To evaluate the changes in surface topography and roughness of stainless steel (SS), nickel-titanium and beta-titanium (ß-Ti) archwires after clinical use and sterilization. SETTINGS AND DESIGN: Thirty wires each of SS, nitinol, and ß-Ti (3M Unitek) were tested in as received, as received and autoclaved, and clinically retrieved then autoclaved conditions. MATERIALS AND METHODS: A sterilization protocol of 134°C for 18 min was performed using an autoclave. Surface topography of specimens from each subgroup was examined using an environmental scanning electron microscope (ESEM model Quanta 200, The Netherlands) at ×100, ×1000, and ×2500 magnifications. Surface roughness was measured using arithmetic mean roughness (Ra) values obtained from optical profilometric scanning (Taylor Hobson, Leicester, UK). STATISTICAL ANALYSIS: Data were analyzed by one-way analysis of variance and Tukey's post-hoc procedures. RESULTS: Scanning electron microscope images revealed an increase in surface irregularities in SS and nitinol wires after clinical use. There was a significant increase in Ra values of SS orthodontic wires after intra-oral exposure (P = 0.0002). CONCLUSION: Surface roughness of SS wires increased significantly after clinical use. Autoclave sterilization did not affect considerably on surface characteristics of any archwire.

Impact of psoriasis on patients' work and productivity: a retrospective, matched case-control analysis.

BACKGROUND: Psoriasis negatively impacts patient quality of life; however, the impact on work and productivity is not well known. OBJECTIVE: To determine the impact of psoriasis on work and productivity using data from the National Health and Wellness Survey (NHWS). METHODS: Data collected from 40 730 adults who completed the NHWS between 1 May and 30 June 2004, of whom 1127 had psoriasis, were analyzed. Psoriasis patients and a matched cohort of non-psoriasis patients were identified to assess the impact of psoriasis on work and productivity. RESULTS: Psoriasis patients were more likely to have missed work for health-related reasons (p < 0.05), had significantly more health-related work productivity impairment (p < 0.001), more overall work impairment (p < 0.001), and more impairment in activity other than work (p < 0.001) than non-psoriasis patients. CONCLUSIONS: The results of this large-scale national survey suggest that psoriasis has a significant negative impact on overall work productivity.

The burden of autoimmune disease: a comparison of prevalence ratios in patients with psoriatic arthritis and psoriasis.

BACKGROUND: Current research has confirmed that many inflammatory autoimmune (AI) diseases are due to derangements in multiple cytokine pathways. Some of these cytokines appear to play comparable key roles across diseases, suggesting that a similar underlying systemic inflammatory cascade could be responsible for various disease states. A recent study supports the hypothesis of a common cytokine-based pathology by showing that having one AI disease significantly increased the risk of having another AI disease. Psoriasis is an AI, manifesting as a chronic inflammatory skin condition and is clearly associated with other conditions, most obviously psoriatic arthritis (PsA). OBJECTIVE: We sought to examine whether patients with PsA enrolled in managed health care plans carry a higher AI disease burden than patients with cutaneous psoriasis only (PsO). METHODS: Patients 18 years or older enrolled in a health claims database were classified by two clinical subtypes: PsA and PsO. Control subjects were matched 3:1 to patients with psoriasis on age, sex, census region, and length of previous medical insurance coverage. AI disease diagnoses were identified through International Classification of Diseases, Ninth Revision codes. The association of other AI diseases with each psoriasis cohort was assessed using a prevalence ratio. RESULTS: PsO was associated with a higher prevalence ratio for the 3 gastrointestinal diseases: Crohn disease (1.6 [confidence interval {CI} 1.4-2.0]), ulcerative colitis (1.3 [CI 1.1-1.6]), and inflammatory bowel disease (1.4 [CI 1.2-1.6]). PsA was also associated with a higher prevalence ratio for the gastrointestinal diseases: Crohn disease (2.1 [CI 1.3-3.3]), ulcerative colitis (2.0 [CI 1.3-3.1]), and inflammatory bowel disease (1.8 [CI 1.3-2.5]). Patients with PsA had an increased prevalence ratio associated with giant cell arteritis (4.8 [CI 1.5-15.7]) and pulmonary fibrosis (1.9 [CI 1.2-3.0]). LIMITATIONS: Detection and misclassification biases may have affected these findings. CONCLUSIONS: These findings support the hypothesis that PsA and PsO are associated with development of other AI diseases. The data suggest that evaluating patients with psoriasis for other associated disorders in a prospective manner may be important, because they may be more likely to experience the onset of another AI disease. Treatment planning for these patients could, therefore, require the medical management of more than one AI disease. Further, our data suggest that PsA and PsO may be divergent in ways previously not described that could inform future research.

Psoriasis: cardiovascular risk factors and other disease comorbidities.

The risk factors of cardiovascular disease and other disease comorbidities appear to be more common in patients with psoriasis compared with the general population. To support this concept, the association between psoriasis and cardiovascular disease and other comorbidities was analyzed using data collected from 40 730 patients in the National Health and Wellness Survey (NHWS) during May and June 2004. A case-control study was conducted with data from 1127 patients with psoriasis and a matched cohort of nonpsoriasis patients. Psoriasis patients were significantly more likely to have cardiovascular comorbidities, including hypertension, hypercholesterolemia, and diabetes, compared with nonpsoriasis patients. Other comorbidities significantly associated with psoriasis were arthritis, depression, sleep disorder/insomnia, chronic obstructive pulmonary disease, and gastroesophageal reflux disease. Responses to this large survey confirm that patients with psoriasis have a higher rate of cardiovascular risk factors and other comorbidities compared with patients without psoriasis.

Comparison of employability outcomes among patients with early or long-standing rheumatoid arthritis.

OBJECTIVE: To compare employability between patients with early and long-standing rheumatoid arthritis (RA) and examine the relationships between improvement in employability and disease stage after adjustment for demographic characteristics, disease activity, physical functioning, and response to therapy. METHODS: We evaluated the employability data from 2 double-blind, randomized, placebo-controlled studies of infliximab plus methotrexate (MTX) in patients with RA. Patients were incomplete responders to MTX in 1 study and had never taken MTX in the other study. Patients age <65 years were categorized as having early RA (< or =3 years disease duration) or long-standing RA (>3 years disease duration). Physical functioning was assessed using the Health Assessment Questionnaire (HAQ) and clinical response was determined based on the American College of Rheumatology 20% improvement criteria (ACR20). RESULTS: Patients with early RA were more likely to be employable at baseline than those with long-standing RA, even after adjusting for baseline HAQ scores. Among patients who were not employable at baseline but achieved an ACR20 response after 1 year of treatment, after adjusting for baseline HAQ score, the patients with early RA who had never taken MTX were 3 times more likely to become employable compared with those with long-standing RA who had an incomplete response to MTX at baseline. CONCLUSION: In 2 clinical trials, patients with early RA were more likely to show improved employment outcomes after treatment than those with long-standing RA, suggesting intervention as early as possible in the disease course maximizes an individual patient's employment potential.

Systemic sclerosis prevalence and comorbidities in the US, 2001-2002.

OBJECTIVE: Large, population-based assessments of systemic sclerosis (SSc) prevalence and comorbidity in the United States (US) are rare. We explored autoimmune disease and other comorbidity patterns among SSc patients in the US from 2001 to 2002 and compared these with controls. RESEARCH DESIGN AND METHODS: Two US datasets with patient-level medical and drug claims were used to assess SSc prevalence and comorbidity: IMS Health Integrated Administrative Claims Database (IMS Health) and the MarketScan Commercial Claims and Encounters Database (MarketScan). SSc patients and comorbidities were identified by International Classification of Diseases (ICD), 9th revision diagnostic codes appearing on medical claims. Patients without SSc diagnostic codes (controls) were selected and matched 4:1 to SSc patients based on sex, age, Census Bureau region, and previous insurance coverage. The prevalence relative risk (RR) statistic compared comorbidity occurrence between SSc patients and controls, with 95% confidence intervals estimated using the Mantel-Haenszel method. Several sensitivity analyses tested methods used for identifying SSc cases and the prevalence of comorbidities. RESULTS: In both databases, SSc prevalence was 0.05% using the standard population model, 0.03% under sensitivity analysis. Among SSc patients the risks for inflammatory bowel disease (IBD) and multiple sclerosis (MS) were notably higher across datasets than for those without SSc: RR 3.2-6.6 for MS, RR 2.1-2.2 for IBD, in MarketScan and IMS Health, respectively (p < 0.05 for all). The chronic disease burden of SSc patients was much higher than that of controls, as confirmed by two chronicity measures (Chronic Disease Score, Elixhauser Comorbidity Index). The risks for cardiovascular, renal, liver and several neuropsychiatric diseases were higher for SSc patients across both datasets. Sensitivity analyses supported these findings. CONCLUSIONS: These data provide a population-based estimate of US prevalence of SSc and document the higher risk for certain other autoimmune diseases among SSc patients when compared to controls. Patients with SSc also had a higher chronic disease burden than those without SSc. These findings are limited by the unknown validity of ICD-9 codes for SSc case identification, unbalanced regional representation, and a likely 'healthy worker' effect in these databases.

Autoimmune disease concomitance among inflammatory bowel disease patients in the United States, 2001-2002.

BACKGROUND: Recent studies suggest that inflammatory bowel disease (IBD) may share an underlying pathogenesis with other autoimmune diseases. METHODS: Two United States data sets with patient-level medical and drug claims were used to explore the occurrence of autoimmune diseases in patients with IBD, particularly Crohn's disease (CD) and ulcerative colitis (UC), with that in controls. From 2001 to 2002 IBD patients were identified using International Classification of Diseases, 9th revision, diagnosis codes in the IMS Health Integrated Administration Claims Database and the Market Scan Commercial Claims and Encounters Database. Controls were selected by matching on sex, age, Census Bureau region, and length of previous medical insurance coverage. Odds ratios (ORs) evaluated the risk relationship between IBD patients and controls within an estimated Mantel-Haenszel 95% confidence interval. Sensitivity analysis tested the case identification method used to select IBD patients. RESULTS: The risk for ankylosing spondylitis (AS) was substantially increased across both data sets: OR (95% confidence interval [CI]) of 7.8 (5.6-10.8) in IMS Health and 5.8 (3.9-8.6) in MarketScan. The risk for rheumatoid arthritis (RA) was 2.7 (2.4-3.0) and 2.1 (1.8-2.3), respectively; for multiple sclerosis (MS); the ORs were 1.5 (1.2-1.9) and 1.6 (1.2-2.1), respectively. There was no increased risk for type 1 diabetes mellitus, and the results for psoriatic arthritis (PsA) were inconsistent. The sensitivity analysis supported these findings. CONCLUSIONS: A much higher risk for RA, AS, PsA, and MS was observed in IBD patients compared with controls. Prospective epidemiologic studies are needed to confirm these findings and explore the pathogenic mechanism of this relationship.

A case-control study of anaemia in patients with rheumatoid arthritis treated with disease-modifying antirheumatic drugs in an adult population in the US: prevalence and impact on healthcare utilisation.

OBJECTIVE: The objective of this study was to estimate the prevalence of anaemia and its impact on healthcare utilisation in patients with rheumatoid arthritis (RA). METHODS: Patients with claims for moderate-to-severe RA (ICD-9 code 714.x) treated with disease-modifying antirheumatic drugs as well as controls without RA matched for age, gender and time in plan were selected from the MarketScan Research Database. Anaemia was identified by ICD-9 codes 280.x, 285.2x, 281.9, 285.9 and 284.8. The prevalence ratio and 95% confidence interval (CI) for anaemia among RA patients versus controls were estimated. Overall disease burden was measured using the Elixhauser Comorbidity Index (ECI). RESULTS: The prevalence ratio for anaemia in RA patients was 2.2 (95% CI 2.1-2.4). Mean ECI was higher in RA (2.26) compared with control (1.02) patients (p<0.001), and RA patients with anaemia had a higher ECI compared with those without anaemia (3.95 vs. 2.08; p<0.001). Total healthcare costs in RA patients with anaemia were approximately twice those of RA patients without anaemia. CONCLUSIONS: The prevalence of clinically diagnosed anaemia in RA patients in the claims database was 2.2 times higher than that in the comparable non-RA control group. RA patients with anaemia had significantly higher levels of co-morbidity and healthcare costs than RA patients without anaemia.

Adverse drug events in infliximab-treated patients compared with the general and psoriasis populations.

INTRODUCTION: Infliximab is indicated for severe plaque psoriasis (PsO). The investigators compared safety event rates in infliximab PsO trials with those of the general United States and PsO populations. METHODS: Integrated data (n=1373 patients) were compared with external databases. RESULTS: The analyses reported here are based on 1106 patient years and 116 patient years of follow-up in the infliximab group and the placebo group, respectively. The standardized mortality ratio in infliximab-treated patients (0.17 [95% confidence interval [CI]: 0.00-0.92], 1 patient died) was lower than that of the general PsO population. No death occurred in the placebo group. Comparing with the psoriasis population, the standardized incidence ratios (SIRs) for hospitalization were 1.16 (95% CI: 0.92-1.43) in infliximab-treated patients and 1.07 (95% CI: 0.46-2.11) in placebo-treated patients. For serious infection, the SIRs were 1.28 (95% CI: 0.78-1.97) in infliximab-treated patients and 1.47 (95% CI: 0.18-5.32) in placebo patients. The incidence of tuberculosis (TB) among infliximab-treated patients was 0.18 per 100 patient-years (95% CI: 0.02-0.65). No TB occurred in the placebo group. Standardized incidence ratio for malignancy (excluding nonmelanoma skin cancers) was 0.39 (95% CI: 0.05-1.42; 2 malignancies) in infliximab-treated patients. No malignancy occurred in the placebo group. LIMITATIONS: Exclusion criteria in clinical studies may bias selection of subjects who are healthier than the general population. Additionally, the limited number of patients followed over a maximum of 1 year can limit the ability to detect infrequent events or those events that require prolonged follow-up to detect. Nonmelanoma skin cancers were excluded from the analysis. Finally, populations and adverse event definitions may have differed in external databases and studies. CONCLUSION: Based on the data from external databases, mortality, hospitalization, and serious infection rates in infliximab-treated patients were generally comparable to or less than that of the PsO population. Internal malignancy rates were similar to that expected in the general US population. However, the limitations of these data must be considered when compared with the totality of the safety profile of infliximab generated across all indications.

Presenting results of probabilistic sensitivity analysis: the incremental benefit curve.

Cost-effectiveness acceptability curves have become a common way of presenting the results of probabilistic sensitivity analysis. However, these curves do not provide information on what the loss of welfare or net benefit (NB) is for cases where a given intervention is not the optimal one. We describe an alternate approach to presenting the results of probabilistic sensitivity analysis called the incremental benefit curve that presents the entire distribution of incremental NB of each intervention for a given WTP value. The incremental benefit curve provides the decision maker information regarding the potential welfare loss with a given intervention for scenarios in which it is not the optimal intervention, and thus would be a useful complement to the acceptability curve.

Association of anemia and physical disability among patients with rheumatoid arthritis.

OBJECTIVE: To evaluate the relationship between hemoglobin concentration and physical disability in patients with rheumatoid arthritis (RA). METHODS: Data were derived from 2495 patients with RA enrolled in 3 clinical trials (ATTRACT, ASPIRE, and START) and treated with infliximab (3 to 10 mg/kg) plus methotrexate (MTX), or MTX plus placebo. The association of hemoglobin and the Health Assessment Questionnaire (HAQ) score was assessed at baseline (n = 2471) and Week 22 (n = 2458) by Spearman correlation, and multivariate linear regression models were employed to control for confounding effects from demographic and other clinical variables. A logistic regression model was used to estimate the odds ratio (OR) for a clinically meaningful improvement (> or = 0.25 point increase) in HAQ associated with a > or = 1 g/dl improvement in hemoglobin from baseline at Week 22. RESULTS: About 37% of patients with RA had anemia based on World Health Organization criteria: hemoglobin < 12 g/dl in women (39%) and < 13 g/dl in men (32%). Low hemoglobin level was significantly associated with more severe physical disability at baseline (p < 0.001), and both male and female patients with anemia had more severe disability at baseline. Improvement in hemoglobin after treatment at Week 22 was an independent contributor to improvement in HAQ, and a > or = 1 g/dl improvement in hemoglobin after treatment was associated with a clinically meaningful improvement in the HAQ score at Week 22 (OR 1.43, 95% CI 1.10-1.86; p < 0.01). CONCLUSION: Anemia is one of the independent factors contributing to physical disability in patients with RA. Improvement in anemia following effective RA treatment may play an independent role in improving physical function.

The impact of infliximab treatment on quality of life in patients with inflammatory rheumatic diseases.

In this study, we compare the health-related quality of life (HRQoL) of patients with moderate-to-severe rheumatoid arthritis (RA), psoriatic arthritis (PsA), and ankylosing spondylitis (AS), and study the effect of treatment with infliximab on the HRQoL of patients with these diseases. Short Form Health Survey-36 (SF-36) data from the placebo-controlled phases of 4 studies of infliximab in patients with inflammatory rheumatic diseases (n = 1990) were evaluated. Data came from the Anti-TNF Trial in Rheumatoid Arthritis with Concomitant Therapy (ATTRACT) (n = 428), the Safety Trial for Rheumatoid Arthritis with REMICADE Therapy (START) (n = 1083), the Ankylosing Spondylitis Study for the Evaluation of Recombinant Infliximab Therapy (ASSERT) (n = 279), and the Infliximab Multinational Psoriatic Arthritis Clinical Trial II (IMPACT II) (n = 200). SF-36 assessments were made at weeks 0, 10, 30, and 54 in ATTRACT, weeks 0, 6, and 22 in START, weeks 0, 12, and 24 in ASSERT, and weeks 0 and 14 in IMPACT II. All patient populations had significantly impaired physical aspects of HRQoL at baseline relative to the general population of the United States, and the magnitude of impairment was similar across the diseases. Mean baseline physical component summary scores were 29 in the RA cohort, 32 in the PsA cohort, and 29 in the AS cohort. In all 3 diseases, patients who received infliximab showed significant improvement in physical component summary scores compared with those who received placebo. The magnitude of the difference of improvement (effect size, 95%CI) between infliximab and placebo groups was similar in the AS (10.1, 9.2-11.0), PsA (8.6, 7.8-9.4), and RA (10.1, 9.2-11.0) cohorts. Patients with RA and those with PsA treated with infliximab also showed greater improvement in the mental component summary score than those in the placebo group with an effect size of 4.6 (4.2-5.1) in RA and 2.7 (2.4-3.1) in PsA. Patients in large randomized controlled studies of infliximab in RA, PsA, and AS had similar impairment in physical aspects of HRQoL at baseline and showed significantly greater improvement in HRQoL after treatment with infliximab.

Infliximab treatment improves productivity among patients with moderate-to-severe psoriasis.

This study examined the impact of infliximab maintenance therapy on productivity in patients with moderate-to-severe psoriasis. Patients from the multicentre, double-blind, placebo-controlled EXPRESS study (n = 378) were randomised to receive infusions of placebo or infliximab 5 mg/kg at weeks 0, 2, and 6 and every 8 weeks through week 46, with placebo crossover to infliximab at week 24. Main outcome measures were a 10-cm productivity visual analog scale (VAS), role-physical and role-emotional domain scores of the Short Form 36-Item questionnaire (SF-36), and Dermatology Life Quality Index (DLQI) scores. The productivity VAS score was 5.9 cm at baseline. Mean change through week 10 with infliximab was significantly greater than that with placebo (2.7 cm vs. - 0.1 cm) and was sustained through week 24. Similar trends were observed for SF-36 scores. The proportion of patients whose skin condition prevented them from working and/or studying per DLQI scores decreased through week 10 with infliximab (12.1% and 1.4%, respectively), but increased slightly with placebo (9.1% and 11.6%, respectively). At week 50, improvements in productivity and SF-36 scores were sustained with infliximab. In placebo patients who crossed over to infliximab, these scores improved and approached those seen with infliximab at week 50. Infliximab significantly improved productivity and ability to work in psoriasis patients.

Changes in biomarkers of inflammation and bone turnover and associations with clinical efficacy following infliximab plus methotrexate therapy in patients with early rheumatoid arthritis.

OBJECTIVE: To determine if changes in biomarkers of inflammation and bone turnover in response to treatment with infliximab plus methotrexate (MTX) versus MTX alone are associated with improvement in clinical measures of signs, symptoms, and structural damage in early rheumatoid arthritis. METHODS: Sera were collected from patients in the ASPIRE study who received 3 mg/kg (n = 48) or 6 mg/kg infliximab plus MTX (n = 55), or MTX alone (n = 41). Several baseline biomarker levels correlated with changes in median percentage of American College of Rheumatology improvement (ACR-N), 50% improvement in ACR response (ACR50), and van der Heijde-modified Sharp score (vdHSS) at Week 54. RESULTS: Infliximab plus MTX treatment resulted in more rapid decreases in levels of matrix metalloproteinase-3 (MMP-3), intercellular cell adhesion molecule-1, interleukin 8 (IL-8), and tumor necrosis factor-a than treatment with MTX alone. Baseline levels and decreases from baseline to Weeks 6 and 54 in MMP-3 correlated with improvement in ACR-N response at Week 54. An increase in IL-8 levels from baseline to Week 54 correlated with worsening in vdHSS at Week 54 in the MTX-alone group. Regression analysis of markers at baseline showed that MMP-3 was the only variable associated with ACR50 response and less worsening in vdHSS at Week 54. CONCLUSION: Treatment with infliximab plus MTX resulted in a rapid decrease in inflammation markers. MMP-3 levels at different timepoints were consistently associated with clinical improvements at Week 54 in the infliximab plus MTX group, while increases in IL-8 levels correlated with a worsening in vdHSS at Week 54 in the MTX-alone group.