M. Elaine Husni

Group for Research and Assessment of Psoriasis and Psoriatic Arthritis 2015 Treatment Recommendations for Psoriatic Arthritis.

To update the 2009 Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) treatment recommendations for the spectrum of manifestations affecting patients with psoriatic arthritis (PsA).

Cardiovascular Safety of Celecoxib, Naproxen, or Ibuprofen for Arthritis

BACKGROUND The cardiovascular safety of celecoxib, as compared with nonselective nonsteroidal antiinflammatory drugs (NSAIDs), remains uncertain. METHODS Patients who required NSAIDs for osteoarthritis or rheumatoid arthritis and were at increased cardiovascular risk were randomly assigned to receive celecoxib, ibuprofen, or naproxen. The goal of the trial was to assess the noninferiority of celecoxib with regard to the primary composite outcome of cardiovascular death (including hemorrhagic death), nonfatal myocardial infarction, or nonfatal stroke. Noninferiority required a hazard ratio of 1.12 or lower, as well as an upper 97.5% confidence limit of 1.33 or lower in the intention-to-treat population and of 1.40 or lower in the on-treatment population. Gastrointestinal and renal outcomes were also adjudicated. RESULTS A total of 24,081 patients were randomly assigned to the celecoxib group (mean [±SD] daily dose, 209±37 mg), the naproxen group (852±103 mg), or the ibuprofen group (2045±246 mg) for a mean treatment duration of 20.3±16.0 months and a mean follow-up period of 34.1±13.4 months. During the trial, 68.8% of the patients stopped taking the study drug, and 27.4% of the patients discontinued follow-up. In the intention-to-treat analyses, a primary outcome event occurred in 188 patients in the celecoxib group (2.3%), 201 patients in the naproxen group (2.5%), and 218 patients in the ibuprofen group (2.7%) (hazard ratio for celecoxib vs. naproxen, 0.93; 95% confidence interval [CI], 0.76 to 1.13; hazard ratio for celecoxib vs. ibuprofen, 0.85; 95% CI, 0.70 to 1.04; P<0.001 for noninferiority in both comparisons). In the on-treatment analysis, a primary outcome event occurred in 134 patients in the celecoxib group (1.7%), 144 patients in the naproxen group (1.8%), and 155 patients in the ibuprofen group (1.9%) (hazard ratio for celecoxib vs. naproxen, 0.90; 95% CI, 0.71 to 1.15; hazard ratio for celecoxib vs. ibuprofen, 0.81; 95% CI, 0.65 to 1.02; P<0.001 for noninferiority in both comparisons). The risk of gastrointestinal events was significantly lower with celecoxib than with naproxen (P=0.01) or ibuprofen (P=0.002); the risk of renal events was significantly lower with celecoxib than with ibuprofen (P=0.004) but was not significantly lower with celecoxib than with naproxen (P=0.19). CONCLUSIONS At moderate doses, celecoxib was found to be noninferior to ibuprofen or naproxen with regard to cardiovascular safety. (Funded by Pfizer; ClinicalTrials.gov number, NCT00346216 .).

Rationale, design, and governance of Prospective Randomized Evaluation of Celecoxib Integrated Safety versus Ibuprofen Or Naproxen (PRECISION), a cardiovascular end point trial of nonsteroidal antiinflammatory agents in patients with arthritis

BACKGROUND Pain management in patients with osteoarthritis or rheumatoid arthritis often requires long-term use of nonsteroidal antiinflammatory drugs (NSAIDs). However, the relative cardiovascular safety of these therapies remains uncertain. METHODS The Prospective Randomized Evaluation of Celecoxib Integrated Safety versus Ibuprofen Or Naproxen (PRECISION) trial will evaluate the cardiovascular safety of celecoxib, ibuprofen, and naproxen. Approximately 20,000 patients with symptomatic osteoarthritis or rheumatoid arthritis at high risk for, or with, established cardiovascular disease will be randomized in this double-blind, triple dummy, multinational, multicenter study. The primary end point is the composite of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke. The trial will continue until 762 primary events occur with at least 18 months follow-up. Noninferiority of any of the regimens will require a 97.5% upper CI of the hazard ratio (HR) < or =1.33 and point estimate < or =1.12 for both intent-to-treat (ITT) and modified ITT populations. CONCLUSION PRECISION, the first study of patients with high cardiovascular risk chronically treated with a cyclooxygenase-2 selective inhibitor or nonselective NSAID, will define the relative cardiovascular safety profile of celecoxib, ibuprofen, and naproxen and provide data to help guide NSAID use for pain management for this population.

Recognizing and managing comorbidities in psoriatic arthritis.

Purpose of reviewMany patients with psoriatic arthritis (PsA) have additional medical problems that can have an impact on morbidity and mortality. The goal of this review is to summarize the available evidence to date on the association of medical comorbidities with PsA and the implications these comorbidities have on prognosis, therapy selection and treatment response. Recent findingsCardiovascular disease, metabolic syndrome, obesity, diabetes, fatty liver disease Crohns disease, ophthalmic disease, depression and anxiety are common comorbidities associated with PsA. Additional comorbidities may include an elevated risk for malignancy and osteoporosis; however, fewer studies have addressed these issues and the data available are sometimes conflicting. SummaryAll clinicians caring for patients with PsA should be aware of the relevant comorbidities affecting patients with PsA and should have an understanding of how these comorbidities affect management.

Do Acute-Phase Reactants Predict Response to Glucocorticoid Therapy in Retroperitoneal Fibrosis?

OBJECTIVE To determine the value of the erythrocyte sedimentation rate (ESR) and the C-reactive protein (CRP) level at the time of diagnosis for predicting radiographic response to glucocorticoid therapy in patients with retroperitoneal fibrosis (RFP). METHODS Data were collected retrospectively for 37 patients with an established diagnosis of RFP (the diagnosis was proven by biopsy in 31 patients), all of whom met the following inclusion criteria: 1) availability of a recorded baseline ESR and/or CRP level and results of computed tomography or magnetic resonance imaging, 2) availability of followup CRP level and/or ESR with radiographic imaging 12-24 weeks after initiation of therapy, and 3) treatment with prednisone monotherapy at a starting dosage of 40-60 mg daily. Patients were divided into 2 therapeutic response groups: group 1 showed radiographic regression, and group 2 showed no change or radiographic progression. Any progression or regression was determined by an estimated change of > or =25%. RESULTS The median baseline CRP levels were 2.2 mg/dl (interquartile range [IQR] 1.4-8.0) in group 1 and 1.2 mg/dl (IQR 0.8-4.1) in group 2 (P = 0.35). The median baseline ESR in group 1 was 57.5 mm/hour (IQR 39.2-102.5), which was not statistically different from the median ESR in group 2 (58 mm/hour [IQR 33-66]). The mean CRP level and ESR tended to be higher in patients with radiographic regression, but these differences failed to reach statistical significance. Spearmans correlation coefficient revealed no correlation between the baseline CRP level (r = -0.11, P = 0.51) or ESR (r = -0.06, P = 0.71) and the radiographic response. CONCLUSION The ESR and CRP level at baseline are poor predictors of a therapeutic response to glucocorticoid therapy in patients with RPF.

Irreversible heavy chain transfer to hyaluronan oligosaccharides by tumor necrosis factor stimulated gene-6

Background: TSG-6 transfers heavy chains from inter-α-inhibitor to hyaluronan. Results: Heavy chain transfer to hyaluronan by TSG-6 is reversible for high molecular weight hyaluronan but irreversible for hyaluronan oligosaccharides. Conclusion: High molecular weight hyaluronan functions as both a heavy chain acceptor and a heavy chain donor, whereas hyaluronan oligosaccharides function only as heavy chain acceptors. Significance: Hyaluronan oligosaccharides have potential to remove heavy chains from pathological hyaluronan. The covalent transfer of heavy chains (HCs) from inter-α-inhibitor (IαI) to hyaluronan (HA) via the protein product of tumor necrosis factor-stimulated gene-6 (TSG-6) forms the HC-HA complex, a pathological form of HA that promotes the adhesion of leukocytes to HA matrices. The transfer of HCs to high molecular weight (HMW) HA is a reversible event whereby TSG-6 can shuffle HCs from one HA molecule to another. Therefore, HMW HA can serve as both an HC acceptor and an HC donor. In the present study, we show that transfer of HCs to low molecular weight HA oligosaccharides is an irreversible event where subsequent shuffling does not occur, i.e. HA oligosaccharides from 8 to 21 monosaccharide units in length can serve as HC acceptors, but are unable to function as HC donors. We show that the HC-HA complex is present in the synovial fluid of mice subjected to systemic and monoarticular mouse models of rheumatoid arthritis. Furthermore, we demonstrate that HA oligosaccharides can be used, with TSG-6, to irreversibly shuffle HCs from pathological, HMW HC-HA to HA oligosaccharides, thereby restoring HC-HA matrices from the inflamed joint to their normal state, unmodified with HCs. This process was also effective for HC-HA in the synovial fluid of human rheumatoid arthritis patients (in vitro).

Relationship Between Metabolic Syndrome and Carotid Intima-Media Thickness: Cross-Sectional Comparison Between Psoriasis and Psoriatic Arthritis

To determine the differences in carotid intima‐media thickness (CIMT) between patients with psoriatic diseases with and without metabolic syndrome.

Development of screening tools to identify psoriatic arthritis

Psoriatic arthritis (PsA) is an inflammatory arthritis associated with psoriasis that follows an indolent and progressive course. A delay in diagnosis and treatment may lead to irreversible changes such as erosive arthritis, which lead to permanent physical disability and deformity. Administration of a well-designed screening tool can increase detection of PsA and help determine the prevalence of PsA in a given population. Several tools have been developed to help clinicians screen for PsA. Members of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis recently led an effort to develop and validate three PsA screening tools: the Psoriatic Arthritis Screening and Evaluation tool, the Psoriasis Epidemiology Screening Tool, and the Toronto Psoriatic Arthritis Screen.

Comorbidities in Psoriatic Arthritis.

Epidemiologic studies have shown that, in patients with psoriatic arthritis (PsA), associated comorbidities may occur more frequently than expected. This article discusses related comorbidities in patients with PsA. Identifying these comorbidities may affect the management and treatment decisions for these patients to ensure an optimal clinical outcome. All health care providers caring for patients with PsA should be aware of the relevant comorbidities and should have an understanding of how these comorbidities affect management. The common comorbidities include cardiovascular disease, metabolic syndrome, obesity, diabetes, fatty liver disease, inflammatory bowel disease, ophthalmic disease, kidney disease, osteoporosis, depression, and anxiety.

Managing Comorbid Disease in Patients with Psoriatic Arthritis

Psoriatic arthritis (PsA) is a unique type of inflammatory arthritis that is associated with skin psoriasis. The concept that PsA is simply a skin and joint disease has been challenged by large epidemiologic studies that link PsA with substantial comorbidity. Important comorbidities related to PsA include premature cardiovascular disease, infectious complications, malignancy risk, osteoporosis, and reduced quality of life. This review focuses on the prevalent comorbid diseases in patients with PsA and highlights how the presence of these associated comorbidities can affect the management of these patients.