Incidence of gastrointestinal bleeding in most populations is
about 1 per 1,000 inhabitants. More than 65% of all bleeding
episodes are associated with drug use. The most often involved
are ...non-steroidal antiinflammatory drugs and low doses of
acetyl-salicylic acid. The mortality within the first month after
the bleeding episode is about 10–12%, and has not significantly
changed in the last decade. Therefore, bleeding prevention is
of major importance. Appropriate selection of patients, proper
drug choice, application of lowest efficient doses of potentially
ulcerogenic drugs, and use of drugs that inhibit gastric acid
secretion remain cornerstone preventive measures of gastrointestinal
bleeding.
Hormone D and its analogues display immunomodulatory activities providing a beneficial effect in immunoinflammatory diseases. The aim of this study was to assess the effect of alfacalcidol treatment ...on superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) activity and glutathione (GSH) and malondialdehyde (MDA) levels in patients with active RA. Sixteen patients with active RA and twenty controls were enrolled in the study. Blood samples were taken before and after 12 weeks of alfacalcidol therapy (2 ?g/day). Oxidative stress parameters were determined spectrophotometrically and by flow cytometry assessment. Disease activity was assessed using DAS28 score. The results revealed that alfacalcidol treatment, significantly (p = 0.04) reduced SOD activity and CAT activity (p = 0.001) in RA patients. The activity of GPx was significantly lower in RA patients before treatment, compared to controls (p = 0.04). After therapy, GPx activity was restored to control levels, and GSH levels were significantly reduced (p = 0.01). MDA levels in patients at the beginning of the study protocol, remained significantly elevated compared to controls (p = 0.01). Alfacalcidol treatment decreased MDA levels in patients (p = 0.19). Furthermore, 12-weeks alfacalcidol therapy, changed the response of RA patients? PBMC to stimulation preventing the O2 - production and mitochondrial membrane depolarisation. After alfacalcidol treatment, significant clinical improvement was observed.
nema
The aim was to update the 2009 European League against Rheumatism (EULAR) recommendations for the treatment of systemic sclerosis (SSc), with attention to new therapeutic questions. Update of the ...previous treatment recommendations was performed according to EULAR standard operating procedures. The task force consisted of 32 SSc clinical experts from Europe and the USA, 2 patients nominated by the pan-European patient association for SSc (Federation of European Scleroderma Associations (FESCA)), a clinical epidemiologist and 2 research fellows. All centres from the EULAR Scleroderma Trials and Research group were invited to submit and select clinical questions concerning SSc treatment using a Delphi approach. Accordingly, 46 clinical questions addressing 26 different interventions were selected for systematic literature review. The new recommendations were based on the available evidence and developed in a consensus meeting with clinical experts and patients. The procedure resulted in 16 recommendations being developed (instead of 14 in 2009) that address treatment of several SSc-related organ complications: Raynaud's phenomenon (RP), digital ulcers (DUs), pulmonary arterial hypertension (PAH), skin and lung disease, scleroderma renal crisis and gastrointestinal involvement. Compared with the 2009 recommendations, the 2016 recommendations include phosphodiesterase type 5 (PDE-5) inhibitors for the treatment of SSc-related RP and DUs, riociguat, new aspects for endothelin receptor antagonists, prostacyclin analogues and PDE-5 inhibitors for SSc-related PAH. New recommendations regarding the use of fluoxetine for SSc-related RP and haematopoietic stem cell transplantation for selected patients with rapidly progressive SSc were also added. In addition, several comments regarding other treatments addressed in clinical questions and suggestions for the SSc research agenda were formulated. These updated data-derived and consensus-derived recommendations will help rheumatologists to manage patients with SSc in an evidence-based way. These recommendations also give directions for future clinical research in SSc.
Objective
To evaluate the efficacy and safety of PF‐06651600 (ritlecitinib), an irreversible inhibitor of JAK3 and the tyrosine kinase expressed in hepatocellular carcinoma (TEC) kinase family, in ...comparison with placebo in patients with rheumatoid arthritis (RA).
Methods
An 8‐week, phase II, double‐blind, parallel‐group study was conducted. Seventy patients who were seropositive for anti–citrullinated protein antibodies and/or rheumatoid factor were randomized 3:2 to receive oral PF‐06651600 (200 mg once daily) or placebo for 8 weeks. Eligible patients had an inadequate response to methotrexate, and the study design allowed up to 50% of patients to have previously received 1 tumor necrosis factor inhibitor that was inadequately effective and/or not tolerated. The primary end point was change from baseline in the Simplified Disease Activity Index (SDAI) score at week 8, assessed by Bayesian analysis using an informative prior distribution for placebo response.
Results
Mean change from baseline in the SDAI score at week 8 was greater in the PF‐06651600 group (−26.1 95% credible interval −29.7, −22.4) than in the placebo group (−16.8 95% credible interval −20.9, −12.7; P < 0.001). Most adverse events (AEs) were mild in severity, and no treatment‐related serious AEs, severe AEs, or deaths were reported. The most common classes of AE were infections and infestations as well as skin and subcutaneous tissue disorders; there was 1 mild case of herpes simplex in the PF‐06651600 group that was considered to be treatment related, which resolved within 3 days without study treatment discontinuation or antiviral therapy.
Conclusion
Treatment with the oral JAK3/TEC inhibitor PF‐06651600 (200 mg once daily) was associated with significant improvements in RA disease activity and was generally well‐tolerated in this small 8‐week study.
In this article, the 2010 European League against Rheumatism (EULAR) recommendations for the management of rheumatoid arthritis (RA) with synthetic and biological disease-modifying antirheumatic ...drugs (sDMARDs and bDMARDs, respectively) have been updated. The 2013 update has been developed by an international task force, which based its decisions mostly on evidence from three systematic literature reviews (one each on sDMARDs, including glucocorticoids, bDMARDs and safety aspects of DMARD therapy); treatment strategies were also covered by the searches. The evidence presented was discussed and summarised by the experts in the course of a consensus finding and voting process. Levels of evidence and grades of recommendations were derived and levels of agreement (strengths of recommendations) were determined. Fourteen recommendations were developed (instead of 15 in 2010). Some of the 2010 recommendations were deleted, and others were amended or split. The recommendations cover general aspects, such as attainment of remission or low disease activity using a treat-to-target approach, and the need for shared decision-making between rheumatologists and patients. The more specific items relate to starting DMARD therapy using a conventional sDMARD (csDMARD) strategy in combination with glucocorticoids, followed by the addition of a bDMARD or another csDMARD strategy (after stratification by presence or absence of adverse risk factors) if the treatment target is not reached within 6 months (or improvement not seen at 3 months). Tumour necrosis factor inhibitors (adalimumab, certolizumab pegol, etanercept, golimumab, infliximab, biosimilars), abatacept, tocilizumab and, under certain circumstances, rituximab are essentially considered to have similar efficacy and safety. If the first bDMARD strategy fails, any other bDMARD may be used. The recommendations also address tofacitinib as a targeted sDMARD (tsDMARD), which is recommended, where licensed, after use of at least one bDMARD. Biosimilars are also addressed. These recommendations are intended to inform rheumatologists, patients, national rheumatology societies and other stakeholders about EULAR's most recent consensus on the management of RA with sDMARDs, glucocorticoids and bDMARDs. They are based on evidence and expert opinion and intended to improve outcome in patients with RA.
Data regarding the treatment of hip osteoarthritis (OA) with collagen-based extracellular bio-scaffolds are lacking. We evaluated the treatment of hip OA with ultrasound guided intraarticular ...injections of Collagen-based Medical Device (CMD).
Forty-four patients with Kellgren-Lawrence grade (KLG) I or II were selected, and 20/44 randomly selected patients (CMD group), were treated with 2 weekly consecutive ultrasound guided intraarticular injections of CMD (MD-HIP, Guna S.p.a. Milan, Italy). An additional 24/44 patients were treated with oral non-steroidal anti-inflammatory drugs (NSAIDs) daily (NSAIDs group). Clinical assessment, X-rays and ultrasound evaluation were performed at baseline, and after 1 month in both groups, and after 3 months in the CMD group. Outcome measures were general pain VAS (0-10), the whole WOMAC score, and the WOMAC specific subscores.
CMD and NSAIDs group were homogenous for age, gender, VAS pain and WOMAC scores. The CMD group had significant improvement of the VAS pain (p<0.0001), global WOMAC score (p<0.0001) and WOMAC function (p<0.0001) from baseline to the 1st month, with further improvement from the 1st to the 3rd month (p<0,001; p<0.01; p<0.03, respectively). Significant improvement in WOMAC pain (p<0.0001) and WOMAC stiffness (p<0.0001) was detected at 1st month, with no significant change at 3rd month. In the NSAIDs group significant improvement in WOMAC function was detected after 1 month (p=0.021) only. No adverse events were recorded in the CMD and NSAIDs group.
The ultrasound guided intraarticular hip injections of CMD resulted in significant improvement in VAS pain and WOMAC scores compared to treatment with oral NSAIDs.
ObjectivesTo determine the causes of death and risk factors in systemic sclerosis (SSc).MethodsBetween 2000 and 2011, we examined the death certificates of all French patients with SSc to determine ...causes of death. Then we examined causes of death and developed a score associated with all-cause mortality from the international European Scleroderma Trials and Research (EUSTAR) database. Candidate prognostic factors were tested by Cox proportional hazards regression model by single variable analysis, followed by a multiple variable model stratified by centres. The bootstrapping technique was used for internal validation.ResultsWe identified 2719 French certificates of deaths related to SSc, mainly from cardiac (31%) and respiratory (18%) causes, and an increase in SSc-specific mortality over time. Over a median follow-up of 2.3 years, 1072 (9.6%) of 11 193 patients from the EUSTAR sample died, from cardiac disease in 27% and respiratory causes in 17%. By multiple variable analysis, a risk score was developed, which accurately predicted the 3-year mortality, with an area under the curve of 0.82. The 3-year survival of patients in the upper quartile was 53%, in contrast with 98% in the first quartile.ConclusionCombining two complementary and detailed databases enabled the collection of an unprecedented 3700 deaths, revealing the major contribution of the cardiopulmonary system to SSc mortality. We also developed a robust score to risk-stratify these patients and estimate their 3-year survival. With the emergence of new therapies, these important observations should help caregivers plan and refine the monitoring and management to prolong these patients’ survival.
Systemic sclerosis (SSc) is a rare connective tissue disorder with highest morbidity and mortality among rheumatologic diseases. Disease progression is highly heterogeneous between patients, implying ...a strong need for individualization of therapy. Four pharmacogenetic variants, namely TPMT rs1800460, TPMT rs1142345, MTHFR rs1801133 and SLCO1B1 rs4149056 were tested for association with severe disease outcomes in 102 patients with SSc from Serbia treated either with immunosuppressants azathioprine (AZA) and methotrexate (MTX) or with other types of medications. Genotyping was performed using PCR-RFLP and direct Sanger sequencing. R software was used for statistical analysis and development of polygenic risk score (PRS) model. Association was found between MTHFR rs1801133 and higher risk for elevated systolic pressure in all patients except those prescribed with MTX, and higher risk for kidney insufficiency in patients prescribed with other types of drugs. In patients treated with MTX, variant SLCO1B1 rs4149056 was protective against kidney insufficiency. For patients receiving MTX a trend was shown for having a higher PRS rank and elevated systolic pressure. Our results open a door wide for more extensive research on pharmacogenomics markers in patients with SSc. Altogether, pharmacogenomics markers could predict the outcome of patients with SSc and help in prevention of adverse drug reactions.
To assess prevalence and change of depression/anxiety symptoms in spondyloarthritis patients and feasibility of depression/anxiety questionnaires. 43 Patients with axial spondyloarthritis (axSpA) and ...27 patients with psoriatic arthritis (PsA) were consecutively recruited. There were 34 patients on biologics and 36 patients on nonbiologics. Patients were not previously treated for depression. The demographic variables, pain, patient global assessment, laboratory, clinical findings, diseases activity scores, Beck Depression Inventory (BDI) and Depression Anxiety and Stress Scale—short version (DASS-21) were collected. The study visits were at the beginning, after 1 month, after 3 and after 6 months. In axSpA and PsA patients on biologics, BDI and DASS-21 were significantly lower compared to nonbiologics group during time. The axSpA patients on biologics had significantly lower BDI and depression severity by BDI at each time point and lower DASS-21 after 1, 3 and 6 months. BDI in PsA patients who received biological therapy was significantly lower after 3 and 6 months. In biologics groups, BDI significantly decreased after 3 months in axSpA patients and after 1 month in PsA patients. In axSpA patients, there was a medium correlation between BDI and axial pain, patient global assessment and disease activity scores. The biological therapy significantly affected the depression/anxiety symptoms in axSpA and PsA during time. BDI moderately correlated with pain and disease activity in axSpA. BDI and DASS-21 are easy to use in daily practice.
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