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ID PMID Title PublicationDate abstract
23537059 Subacute cutaneous lupus erythematosus in the course of rheumatoid arthritis: a relationsh 2013 Jun INTRODUCTION: Drug-induced subacute cutaneous lupus erythematosus (DI-SCLE) is caused by different medicines, first of all: calcium channel blockers, angiotensin converting enzyme inhibitors, thiazides, terbinafine, statins and antagonists of tumor necrosis factor-α (TNF-α). DI-SCLE does not distinguish from idiopathic form of the disease, clinically, histopathologically and immunologically. However, receding of symptoms is observed after recapture of the provoking drug. AIM: To present a patient with rheumatoid arthritis (RA), who developed SCLE after treatment with TNF-α antagonists and rituximab. CASE REPORT: In a 31-year-old woman with RA leucopenia due to treatment with etanercept and adalimumab was observed. Therefore, the treatment was changed to rituximab, but after starting the therapy, erythematous and oedematous skin lesions of an oval or annular shape appeared on the cheeks, auricles, lips and the decolette. Histopathological evaluation of the skin lesions revealed SCLE. Ro/SS-A and La/SS-B antibodies were detected in serum. Regression of skin lesions and hematologic disturbances was achieved after starting corticosteroid therapy. CONCLUSIONS: Co-existence of SCLE with RA should be considered in some patients. The role of TNF-α antagonists and rituximab therapy in induction of idiopathic form of SCLE requires further investigations.
25047498 Systematic review of tofacitinib: a new drug for the management of rheumatoid arthritis. 2014 Jul 1 PURPOSE: The goal of this study was to review and summarize the efficacy and safety of use of tofacitinib for treating rheumatoid arthritis (RA). METHODS: A systematic literature review was conducted to identify English-language articles published through May 2013 within PubMed, ClinicalTrials.gov, and Cochrane Library reporting results from Phase II and Phase III tofacitinib randomized clinical trials. Tofacitinib must have been used as monotherapy or in combination therapy with disease-modifying antirheumatic drugs (DMARDs) in the treatment of RA. Study outcomes had to include at least 1 of the following: American College of Rheumatology (ACR) 20%, 50%, or 70% response rates; tender/swollen joint count; health assessment questionnaire of disability; radiographic outcomes; and drug persistence. FINDINGS: Eight studies (4 Phase II and 4 Phase III trials) were included in the review. Patients with active RA and who were nonresponders to a biologic agent or the nonbiologic DMARD methotrexate were included in these studies. The results of the Phase II trials show that tofacitinib at doses ≥3 mg BID was efficacious among the nonresponders. The results of the Phase III trials, comparing tofacitinib 5 and 10 mg with placebo, show that tofacitinib led to a significant improvement in ACR20 response (P < 0.0001), Health Assessment Questionnaire-Disability Index (P < 0.0001) scores, and ACR50 response (P < 0.0001) after 3 months. The efficacy of tofacitinib was numerically similar to adalimumab. The most common adverse events were infections, infestations, increases in LDL-C and HDL-C levels, and a decrease in neutrophil counts. IMPLICATIONS: Tofacitinib is an efficacious drug for the management of moderate to severe RA among patients with an inadequate response to methotrexate and tumor necrosis factor inhibitors. Long-term studies can help in understanding the risk/benefit profile of tofacitinib.
24886491 Differences in muscle activity during hand-dexterity tasks between women with arthritis an 2014 May 15 BACKGROUND: Impaired hand function is common in patients with arthritis and it affects performance of daily activities; thus, hand exercises are recommended. There is little information on the extent to which the disease affects activation of the flexor and extensor muscles during these hand-dexterity tasks. The purpose of this study was to compare muscle activation during such tasks in subjects with arthritis and in a healthy reference group. METHODS: Muscle activation was measured in m. extensor digitorium communis (EDC) and in m. flexor carpi radialis (FCR) with surface electromyography (EMG) in women with rheumatoid arthritis (RA, n = 20), hand osteoarthritis (HOA, n = 16) and in a healthy reference group (n = 20) during the performance of four daily activity tasks and four hand exercises. Maximal voluntary isometric contraction (MVIC) was measured to enable intermuscular comparisons, and muscle activation is presented as %MVIC. RESULTS: The arthritis group used a higher %MVIC than the reference group in both FCR and EDC when cutting with a pair of scissors, pulling up a zipper and-for the EDC-also when writing with a pen and using a key (p < 0.02). The exercise "rolling dough with flat hands" required the lowest %MVIC and may be less effective in improving muscle strength. CONCLUSIONS: Women with arthritis tend to use higher levels of muscle activation in daily tasks than healthy women, and wrist extensors and flexors appear to be equally affected. It is important that hand training programs reflect real-life situations and focus also on extensor strength.
24585741 Impact of rheumatoid arthritis on receiving a diagnosis of hypertension among patients wit 2014 Sep OBJECTIVE: Despite numerous studies reporting increased cardiovascular disease (CVD) in patients with rheumatoid arthritis (RA), the impact of RA on managing modifiable CVD risk factors remains understudied. We tested the hypothesis that RA is a risk factor for not receiving a hypertension diagnosis. METHODS: Using a cohort design, we studied adult patients with and without RA/inflammatory arthritis from a large academic multispecialty practice. All were seen regularly in primary care and met clinical guideline hypertension criteria, but lacked prior hypertension diagnosis/treatment. The primary outcome was time to International Classification of Diseases, Ninth Revision code for hypertension or elevated blood pressure, or antihypertensive medication prescription. Kaplan-Meier survival curve analysis and Cox proportional hazards modeling were used to examine the impact of RA on diagnosis of hypertension. RESULTS: Among 14,974 patients with undiagnosed hypertension, 201 patients had RA codes. RA patients had equivalent primary care visits and more total visits compared to patients without RA. At the end of the study, the likelihood of hypertension diagnosis was 36% in RA patients compared to 51% in patients without RA. In adjusted Cox models, RA patients had a 29% lower hypertension diagnosis hazard (hazard ratio 0.71, 95% confidence interval 0.55-0.93), reflecting more undiagnosed hypertension than with other comorbidities. CONCLUSION: Among patients meeting guideline-based hypertension criteria, RA patients were less likely to be diagnosed despite more visits than those without RA. Given heightened CVD risks in RA and the importance of hypertension diagnosis as a first step toward controlling risk, rheumatologists should collaborate to improve rates of diagnosis for this modifiable CVD risk factor.
23955819 Results of Mannerfelt wrist arthrodesis for rheumatoid arthritis in relation to the positi 2013 Dec PURPOSE: The wrist is involved early in rheumatoid arthritis and is often severely affected. A stable wrist is crucial to good hand function, which often necessitates a fusion. One of the most commonly used techniques in rheumatoid patients is the Mannerfelt arthrodesis. In this retrospective study the outcome and the patient's subjective satisfaction are presented and compared to other techniques. Also the influence of the position of the wrist following a fusion procedure is analysed. METHODS: Thirty-four wrists were retrospectively analysed using radiological measurements, functional scores such as the Disabilities of the Arm, Shoulder and Hand (DASH) and a pain assessment. The objective function of the hand with the fused wrist was assessed. RESULTS: In 92.6% of wrists the patients rated their satisfaction as good or excellent. The mean DASH score post-operatively was 63.3. Of the wrists, 17 were fixed in a median flexed position of 13° and 17 wrists in a median extended position of 8°. There was no statistically significant correlation between the position of the wrist and the satisfaction or objective function. The rate of fusion was 94.1%. CONCLUSIONS: The Mannerfelt arthrodesis achieves good results and provides a high rate of satisfaction and pain relief in our study. It has major advantages compared to other wrist fusion techniques in the rheumatoid patient. We could not show clear statistical evidence for better results in either a flexed or an extended position, but the ratings of the patients indicated better subjective results with a slightly extended position of the arthrodesis.
23497938 PhIP-Seq characterization of autoantibodies from patients with multiple sclerosis, type 1 2013 Jun Autoimmune disease results from a loss of tolerance to self-antigens in genetically susceptible individuals. Completely understanding this process requires that targeted antigens be identified, and so a number of techniques have been developed to determine immune receptor specificities. We previously reported the construction of a phage-displayed synthetic human peptidome and a proof-of-principle analysis of antibodies from three patients with neurological autoimmunity. Here we present data from a large-scale screen of 298 independent antibody repertoires, including those from 73 healthy sera, using phage immunoprecipitation sequencing. The resulting database of peptide-antibody interactions characterizes each individual's unique autoantibody fingerprint, and includes specificities found to occur frequently in the general population as well as those associated with disease. Screening type 1 diabetes (T1D) patients revealed a prematurely polyautoreactive phenotype compared with their matched controls. A collection of cerebrospinal fluids and sera from 63 multiple sclerosis patients uncovered novel, as well as previously reported antibody-peptide interactions. Finally, a screen of synovial fluids and sera from 64 rheumatoid arthritis patients revealed novel disease-associated antibody specificities that were independent of seropositivity status. This work demonstrates the utility of performing PhIP-Seq screens on large numbers of individuals and is another step toward defining the full complement of autoimmunoreactivities in health and disease.
23594208 Delayed-release prednisone - a new approach to an old therapy. 2013 Jun INTRODUCTION: Despite the widespread use of glucocorticoid (GC) treatment for inflammatory conditions, there remains a need to optimize use by improving efficacy and/or reducing adverse consequences. The most advanced approach, already licensed for clinical use, is delayed-release prednisone. AREAS COVERED: Delayed-release prednisone consists of an inert outer coat containing an inner core of active drug (1, 2, or 5 mg) taken at bedtime (approximately 22:00 h). After a lag time of 4 - 6 h, the coat opens to release prednisone, at the appropriate time to counteract elevated nocturnal levels of pro-inflammatory cytokines associated with the circadian pattern of symptoms seen in rheumatoid arthritis (RA) and other inflammatory conditions. Clinical trials in RA have demonstrated the improved efficacy of delayed-release prednisone with respect to morning stiffness compared with conventional immediate-release prednisone tablets taken in the morning and compared with placebo in patients on disease-modifying antirheumatic treatment; the incidence of adverse events was similar to the comparator. Preliminary studies in polymyalgia rheumatica and asthma suggest that delayed-release prednisone may also have benefits in these conditions. EXPERT OPINION: Delayed-release prednisone offers an effective way to improve the benefit:risk ratio of GC treatment for inflammatory conditions with circadian features.
24575891 Switching of biologic disease modifying anti-rheumatic drugs in patients with rheumatoid a 2014 Apr OBJECTIVES: This study examined total healthcare costs and rates of patients with rheumatoid arthritis (RA) who switch biologic disease-modifying anti-rheumatic drug (bDMARD) therapy in a real world setting. METHODS: A retrospective longitudinal analysis was conducted in patients with RA using IMS PharMetrics Plus database from 1/1/2004 to 3/31/2010. The first-line cohort included patients newly initiated on abatacept or the tumor necrosis factor-alpha inhibitors (anti-TNFs) adalimumab, etanercept, or infliximab, with 12 months of continuous follow-up. The second-line cohort included patients initiating a bDMARD with evidence of a different bDMARD within the previous 2 years and with 12 months of continuous follow-up. Switching was defined as a different bDMARD claim within a 200% gap in days supply from the previous bDMARD claim. Non-switchers stayed on their bDMARD in the follow-up period. Monthly total healthcare costs for switchers and non-switchers and rates of bDMARD switching were examined. Switch rates for each bDMARD were also compared. RESULTS: First-line switchers had significantly higher monthly total healthcare costs after the switch than non-switchers ($3759 vs $2343; p < 0.05), as did second-line switchers ($3956 vs $2616; p < 0.05). First-line abatacept (2.1%) had significantly lower rates of switching compared to adalimumab (9.5%), etanercept (9.0%), and infliximab (5.5%). Second-line abatacept (8.0%) had significantly lower rates of switching compared to adalimumab (16.7%), etanercept (14.4%), and infliximab (14.3%). LIMITATIONS: There are no clinical data available in this database and, therefore, this study did not examine the clinical drivers of healthcare costs and switch rates. CONCLUSIONS: Monthly total healthcare costs were higher for bDMARD switchers following the switch compared to non-switchers. Patients on abatacept switched less frequently than patients on anti-TNFs. This study highlights the need to identify patients who are likely to switch in order to ensure they receive the appropriate therapy which may improve outcomes and decrease healthcare costs.
24497528 Increased risk of chronic obstructive pulmonary disease in patients with rheumatoid arthri 2014 Jul BACKGROUND: The role of autoimmune pathology in development and progression of chronic obstructive pulmonary disease (COPD) is becoming increasingly popular. Our aim was to assess the association between patients with rheumatoid arthritis (RA) and subsequent COPD risk in a nationwide population. METHOD: We conducted a retrospective cohort study using data from the National Health Insurance system of Taiwan. The RA cohort included patients who were newly diagnosed and recruited between 1998 and 2008. Each patient was randomly frequency-matched for age, sex and the year of index date with people without RA from the general population. The newly diagnosed COPD was followed up until the end of 2010. The relative risks of COPD were estimated using Cox proportional hazard models after adjusting for age, sex, index year and comorbidities. RESULT: The overall incidence rate of COPD was 1.74-fold higher in the RA cohort than in the non-RA cohort (5.25 vs. 3.01 per 1000 person-years, 95% confidence interval (CI) = 1.68-1.81). Age-related risk analysis showed an increased incidence of COPD with age in both RA and non-RA cohorts. However, adjusted hazard ratio (HR) maximum was witnessed in the age range of 20-34 years (adjusted HR: 7.67, 95% CI=1.94-30.3), whereas adjusted HR minimum was observed in the oldest age group (>65 years). CONCLUSION: Patients with RA have a significantly higher risk of developing COPD than that of the control population. Further, age-related risk analysis indicated much higher adjusted HR in younger patients although COPD incidence increased with age. It can be hypothesized that in addition to cigarette smoke, RA may be a determining factor for COPD incidence and/or facilitates shortening of the time course for developing COPD. However, further investigation is needed to corroborate this hypothesis.
25429614 Rheumatoid arthritis-associated corneal ulceration with superimposed infection by methicil 2014 Nov 27 BACKGROUND: Severe extra-articular manifestations of rheumatoid arthritis usually occur in advanced stages of the disease. In particular, ocular involvement may lead to inflammatory corneal ulceration, in which therapy is challenging owing to its association with systemic vasculitis. Close collaboration between ophthalmologists and rheumatologists is paramount in providing the best treatment approach in this sight-threatening condition. CASE REPORT: We present a case of seropositive rheumatoid arthritis associated with corneal melting in the absence of other typical clinical manifestations of rheumatoid arthritis flare. The rheumatoid arthritis-associated corneal ulcer was complicated in our case by concomitant infection with methicillin-resistant Staphylococcus aureus, which was treated with intravenous vancomycin after an initial antimicrobial ophthalmic solution proved not to be making adequate improvement in the corneal healing. The recurrent corneal melting appeared to be aggravated by the ophthalmic infection while on immunosuppressive regimen. CONCLUSIONS: In patients on biologic agents, intravenous antibiotics must be considered in addition to ophthalmic eye solution in controlling the infectious process. Excluding concomitant ophthalmic infection is equally important before initiation of high-dose steroid and immunosuppressive regimens.
23861534 Inhibition of spleen tyrosine kinase in the treatment of rheumatoid arthritis. 2013 Sep The pathogenesis of RA is a complex and ever-changing landscape but amid the chaos of the disease process we have found effective treatment regimes. However, our current therapeutics, although targeting various components of both the innate and adaptive immune response, do not result in disease remission. Protein kinase inhibitors are attractive targets due to their ability to influence downstream signalling and their oral bioavailability. Fostamatinib (R788) inhibits spleen tyrosine kinase (Syk) and has been in clinical trials involving both MTX inadequate responders (MTX-IRs) and biologic inadequate responders. Studies on the MTX-IR population revealed ACR20 responses of 67-72% at higher doses (150 mg bd and 100 mg bd), ACR50 responses of 43-57% and ACR70 responses of 28-40%. The trial in the biologic non-responder population showed no efficacy, however, post hoc analyses of the data suggested that a further trial in this population is warranted. The most common adverse events included gastrointestinal effects, hypertension, neutropenia and transaminitis. Many adverse effects were dose responsive and hypertension was amenable to treatment. Upper respiratory tract infections were more likely at higher doses, but no serious infections with tuberculosis, fungi or opportunistic infections were reported. The oral availability of these agents makes them attractive treatment options for our patients, although the literature from the oncology field suggests that patients will only choose the oral route if efficacy is equivalent. Long-term follow-up studies are ongoing and will be critical for rare side effects. The role of these agents in our current arsenal is unclear and economic analyses are awaited.
24448376 The risk of asthma in rheumatoid arthritis: a population-based cohort study. 2014 Jun BACKGROUND: Several studies discussed the relations between asthma and rheumatoid arthritis (RA) but the results were controversial. These studies were either questionnaire based or with small study populations. We aimed to examine the risk of asthma among RA patients in a nationwide population. METHODS: We conducted a cohort study using data from the National Health Insurance system of Taiwan. The RA cohort included 27 602 patients who were newly diagnosed and recruited between 1998 and 2008. Each patient was randomly frequency-matched with three people without RA on age group, sex and the year of index date from the general population. The occurrence of asthma was followed up until the end of 2010. The relative risks of asthma were estimated using Cox proportional hazard models after adjusting for age and comorbidities. RESULT: The overall incidence rate of asthma was 2.07-fold greater in the RA cohort than in the non-RA cohort (4.56 vs. 2.22 per 1000 person-years, 95% CI = 1.99-2.15). Stratified analyses by gender, age group and comorbidity revealed that the risk of asthma associated with RA was higher in females (adjusted hazard ratio (HR) = 2.18, 95% CI = 1.97-2.41), individuals younger than 40 years old (adjusted HR = 3.26, 95% CI = 2.09-5.11) and without comorbidity (adjusted HR = 2.17, 95% CI = 1.97-2.39). CONCLUSION: Patients with RA had a significantly higher risk of developing asthma than healthy people in all sex and age subgroups. Stratified analyses indicated that there was a higher risk in women with RA than in men with RA when compared to their counterpart. Similarly, the HR of asthma associated with RA was higher in younger subjects, although the incidence rate increased with age.
24836652 Mortality after shoulder arthroplasty. 2014 Sep One year post-operative mortality among patients with primary elective total shoulder arthroplasty (ETSA) and traumatic shoulder arthroplasty (TSA) were compared to the general population of a large healthcare system. Standardized mortality ratios (SMRs) and 95% confidence intervals (CIs) were calculated. 614 ETSA patients, 1.0% one year mortality, and 168 TSA patients, 5.4% mortality rate, were evaluated. Patients with ETSA (SMR = 0.4, 95% CI 0.1-0.7) had lower odds of mortality than expected, while patients with TSA (SMR = 1.8, 95% CI 0.6-3.0) did not have higher than expected odds of mortality compared to the reference population. Understanding excess mortality following shoulder arthroplasty surgery allows providers to evaluate current practices and identify ways to optimize patients prior to surgery.
24447441 Certolizumab for rheumatoid arthritis. 2014 May This is a review of the pharmacology of certolizumab pegol and its efficacy and safety in the treatment of patients with rheumatoid arthritis refractory to synthetic disease-modifying anti-rheumatic drugs (DMARDs). Certolizumab is a new anti-TNF-α biologic agent injected subcutaneously with an innovative molecular structure and unique pharmacodynamic and pharmacokinetic properties. Data from controlled clinical trials indicate that the drug is effective in reducing disease activity and disability. It also inhibits radiographic progression. Certolizumab administration has an acceptable safety profile. The clinical data available suggest that the nature of adverse events is generally comparable to that of other TNF-α blockers. Given its rapid onset of action certolizumab presents an attractive alternative therapeutic option for patients with moderate to severe RA refractory to DMARDs.
24952962 Rheumatological diseases and kidneys: a nephrologist's perspective. 2014 Nov Renal involvement is a common occurrence in subjects with rheumatological diseases and can develop either due to the disease itself or secondary to drugs used in the treatment. The prevalence of renal involvement and its severity depends on the underlying disease as well as aggressiveness of the therapy. For most rheumatological diseases, renal involvement heralds a poor prognosis and warrants aggressive immunosuppressive treatment. Thus, it is important to diagnose and manage them at an early stage. On the other hand, patients with primary kidney disease can also develop rheumatological manifestations which need to be differentiated from the former. This article provides the nephrologist's perspective upon various rheumatological disorders and associated renal involvement with the aim of sensitizing the rheumatological community about them, resulting in better management of these subjects.
23979914 The Canadian methotrexate and etanercept outcome study: a randomised trial of discontinuin 2014 Dec OBJECTIVE: To determine if withdrawing methotrexate (MTX) after 6 months of combination etanercept (ETN)+MTX, in MTX-inadequate responders with active rheumatoid arthritis (RA), is non-inferior to continuing ETN+MTX. METHODS: Tumour necrosis factor-inhibitor naïve RA patients with disease activity score 28 (DAS28)≥3.2, swollen joint count≥3, despite stable MTX, were treated with ETN+MTX for 6 months, followed by randomisation to either continue ETN+MTX or switch to ETN monotherapy for an additional 18 months. The primary endpoint was change in DAS28 from 6-month randomisation to 12 months. The non-inferiority margin of change in DAS28 was 0.6, with prespecified analyses (DAS28<3.2 vs DAS28≥3.2). RESULTS: 205 patients were randomised. DAS28 was stable in patients on ETN+MTX and increased slightly in patients on ETN monotherapy from 6 to 12 months. Non-inferiority was not achieved, with an adjusted difference of 0.4 (0.1 to 0.7) between the ETN and the ETN+MTX groups, for the month 6-12 change in DAS28. However, patients who achieved low disease activity (LDA; DAS28<3.2) at 6 months had a similar disease activity at 12 months, whether on monotherapy or combination therapy (DAS28 change 0.7 ETN vs 0.57 ETN+MTX, p=0.8148). Conversely, for patients who did not reach LDA at 6 months, those on ETN monotherapy had increased disease activity at 12 months, while disease activity continued to decrease for patients on combination therapy, at 12 months (DAS28 change 0.4 ETN vs -0.4 ETN+MTX, p=0.0023). CONCLUSIONS: Non-inferiority was not achieved. Withdrawing MTX after 6 months of continuation ETN+MTX in MTX inadequate responders did not yield the same degree of improvement between 6 and 12 months compared with continuing ETN+MTX. TRIAL REGISTRATION: ClinicalTrials.gov-NCT00654368.
24666401 Restoration of peripheral blood natural killer and B cell levels in patients affected by r 2014 Jul Etanercept (ETN) is an anti-tumour necrosis factor (TNF)-α agent used in rheumatoid arthritis (RA) and psoriatic arthritis (PsA). Few studies focused on the effects of anti-TNF-α on peripheral blood cells. We aimed to evaluate peripheral blood cells in RA and PsA patients during ETN treatment and to explore their relationships with disease activity. RA (n = 82) and PsA (n = 32) patients who started ETN were included into the study and evaluated prospectively before the beginning of ETN therapy and after 14, 22, 54 and 102 weeks. Patients were studied in terms of disease activity score on 28 joints (DAS28), clinical response and laboratory findings. Natural killer (NK) cells, B cells and T cells were characterized by immunophenotyping. Both the RA and the PsA patients showed reduced NK and B cell count before ETN treatment compared with controls. A negative correlation was demonstrated between DAS28 and B cell count in RA patients at baseline. Sustained significant increase of NK and B cells up to normal levels was observed in RA and PsA patients along ETN treatment. Increase of NK cell count was associated with a good-moderate clinical response to ETN in both RA and PsA patients. During ETN treatment peripheral blood NK and B cells levels were restored in RA and PsA patients. Correlations between NK and B cells with disease activity were observed, suggesting that those effects could be mediated by ETN treatment.
22841983 Potential roles for CD8(+) T cells in rheumatoid arthritis. 2013 Jan CD8(+) T cells have long been suggested to play a role in rheumatoid arthritis (RA). The current paradigm on the pathogenesis and maintenance of the disease would endorse these cells with predominantly protective and minor influences. However, several animal studies suggest that these cells may have a predominantly proinflammatory (cytotoxic) effect in the disease. Other studies claim otherwise, that they have a mainly regulatory role in inflammatory joints. The evidence in human disease is remarkably scarce. Studies in human samples indicate that CD8(+) T cells play an important role in the establishment of germinal centers observed in nearly 50% of RA patients, which may have a decisive role in the initiation and maintenance of the disease process. The conflicting results of experimental studies, the scarcity of data and the complexity of research needed to unravel these complex interactions may explain the relative oblivion of CD8 cells in the field of arthritis over recent decades. Is this a wise decision or may we run the risk of not finding the key to RA because we search for it where there is light as opposed to its probable location? The present review brings together available data on the potential role of CD8(+) T cells in inflammation, with emphasis on rheumatoid arthritis, hoping to foster interest and fresh research in this area.
25134358 [Mechanisms of the immune system ageing and some age-associated diseases]. 2014 In this paper the concept of homeostenosis (progressive reduction of ability to adapt producing loss of effectiveness) of the immune system is presented as a cause of the system ageing. In particular, the progression of immune system homeostenosis was shown to be associated with previous or ongoing chronic inflammatory diseases, including rheumatoid arthritis, type 2 diabetes, chronic kidney disease and Alzheimer's disease.
24814757 Safety of low- to medium-dose glucocorticoid treatment in rheumatoid arthritis: myths and 2014 May Low- to medium-dose glucocorticoids have been shown to have not only anti-inflammatory but also disease-modifying properties in rheumatoid arthritis. The evidence for the benefit of its early use in combination with disease-modifying antirheumatic drugs underlines the need for a close evaluation of their risk-benefit ratio. Over time, numerous myths and fears about glucocorticoid toxicity in rheumatoid arthritis have arisen from observational studies, and many concerns have been unduly extrapolated from observations with higher-dose treatment. Furthermore, we cannot exclude the possibility of a powerful effect of bias by indication in these studies. Low- to medium-dose glucocorticoid regimens continued to be evaluated in randomized clinical trials, particularly in early disease, but these studies also have relevant methodological limitations in assessing safety, particularly due to small size and/or short duration. At present, the evidence on which to support clear recommendations about glucocorticoid toxicity remains remarkably weak. A large prospective pragmatic trial dedicated to the toxicity of low-dose glucocorticoids is dearly needed. Meanwhile, adherence to recommendations on standardized methodologies for registration and report of glucocorticoid adverse events is essential for improving our knowledge and competence in the best management of these important medications.