Israel Medical Association Journal

Background: Chronic fatigue is common among patients with rheumatoid arthritis (RA), affecting quality of life. Osteoporosis is a prevalent co-morbidity in RA patients.

Objectives: To assess the effect of long-term treatment with tocilizumab on fatigue and bone mineral density (BMD) in RA patients with inadequate response to synthetic or biologic disease-modifying anti-rheumatic drugs. 

Methods: In this multicenter, open-label, non-controlled, single-arm study, patients ≥ 18 years of age received intravenous tocilizumab 8 mg/kg every 4 weeks for 96 weeks. The primary outcome was the change in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue score from baseline to weeks 24, 48, 72, and 96. BMD was assessed before and 96 weeks after treatment. 

Results: The study comprised 145 patients (mean age 53.4 ± 13.4 years, 83.4% women). Of these, 88 (60.7%) completed the 2 year treatment period. The mean FACIT-Fatigue score improved consistently starting from week 4 and showed a statistically significant increase of 5.0 ± 9.7, 6.8 ± 10.5, 7.3 ± 10.9, and 7.3 ± 10.4 from baseline to weeks 24, 48, 72, and 96, respectively (P < 0.0001). Mean BMD of femoral neck and total spine remained stable. Disease activity, acute phase reactants, and composite efficacy measures decreased during the study, while hemoglobin levels increased. Adverse events and serious adverse events were as expected for the known and previously described data.

Conclusions: Tocilizumab therapy for 2 years significantly and clinically decreased fatigue. BMD remained stable and no new safety issue was reported. 

 

Medical practice is a form of art, with each complex detail essential to the welfare of the individuals in the care of the physician. Art and medicine have shared a close relationship in a variety of ways for centuries, as demonstrated by anatomical drawings and textbooks from the 16th century. Leonardo da Vinci, driven by his fascination with the details of the human body and how it functioned, succeeded in creating an anatomical model of the cerebral ventricles and the aorta using molten wax and a glass structure, respectively (Heart and Its Blood Vessels). By using water that contained grass seeds, this experiment enabled him to study blood flow. da Vinci’s engrossment with the complexity of the human body is reflected in many of his drawings, including the famous depiction of the human physique in his drawing of the Vitruvian Man. This drawing, which defines the ideal proportions of the human body and their correlation with geometry, is an example of how artistic and scientific objectives integrate with each other.

Over the last 15 years ultrasound has gained importance for the clinical management of patients with inflammatory rheumatic diseases, especially rheumatoid arthritis. This review summarizes the recent developments and achievements in the use of ultrasound in RA, as well as the unmet needs.

Background: The goals of treatment for rheumatoid arthritis (RA) are remission and low disease activity (LDA). However, many patients do not reach or maintain these targets with regard to disease control. 

Objective: To identify predictive factors of remission/LDA in a cohort of RA patients who started treatment with first line tumor necrosis factor-inhibitors (TNF-i). 

Methods: We included 308 RA patients treated with first line TNF-i for 2 years to evaluate remission/LDA based on the 28-joint disease activity score (DAS28). Predictive factors considered for achievement of remission/LDA were: gender, age at the time of TNF-i treatment, early arthritis, baseline C-reactive protein (CRP) and erythrocyte sedimentation rate levels, RF/anti-citrullinated protein antibody positivity, good/moderate European League Against Rheumatism response at 6 months, co-morbidities, and concomitant disease modifying antirheumatic drugs (DMARDs). Intention to treat, receiver operating characteristic curve, and univariate and multivariate analyses by logistic regression were performed. 

Results: Positive predictors of remission/LDA in both the univariate and the multivariate analyses were: male gender, age at the time of TNF-i treatment ≤ 54 years, negative baseline CRP, and concomitant DMARDs. The presence of any co-morbidity resulted to be a negative predictor of remission/LDA in both the univariate and the multivariate analyses. 

Conclusions: Demographic and clinical features were identified as reliable predictors of both the achievement and the maintenance of treatment targets in a cohort of RA patients treated for 2 years with first line TNF-i. 

 

Background: Non-infectious uveitis (NIU) leads to severe visual impairment, potentially impacting on health-related quality of life (QoL). 

Objectives: To investigate the impact of NIU on QoL.

Methods: Eighty NIU patients and 23 healthy controls completed the 36-item Short-Form Health Survey (SF)-36. The SF-36 values were statistically analyzed to evaluate differences between patients and healthy controls and to identify correlations between SF-36 subscores and clinical/demographic data. 

Results: NIU patients showed a decrease in the physical component summary score (P < 0.0001) compared to healthy controls, while no difference was highlighted in the mental component summary score (P = 0.97). NIU patients showed a decrease in physical functioning (P = 0.008), role-physical (P = 0.003), bodily pain (P = 0.0001), general health (P < 0.0001), and social functioning (P = 0.01). Physical functioning was lower in patients with acute anterior uveitis (AAU) than in those with panuveitis (P = 0.003). No differences were found between patients with bilateral or unilateral NIU, isolated NIU, or NIU associated with systemic diseases and with or without ocular activity. No correlations were identified between best-corrected visual acuity and SF-36 subscores. Physical functioning (P = 0.02), bodily pain (P = 0.004), and social functioning (P = 0.02) were reduced in males versus females. 

Conclusions: QoL is impaired in individuals with NIU, particularly in the physical domains, general health, and social functioning. AAU affects physical functioning more than panuveitis. NIU seems to affect per se QoL disregarding inflammatory activity, visual impairment, and presence of associated systemic diseases.

 

Biomarkers are important for guiding the clinical and therapeutic management of all phases of rheumatoid arthritis because they can help to predict disease development in subjects at risk, improve diagnosis by closing the serological gap, provide prognostic information that is useful for making therapeutic choices and assessing treatment responses and outcomes, and allow disease activity and progression to be monitored. Various biomarkers can be used to identify subjects susceptible to the disease and those with pre-clinical rheumatoid arthritis before the onset of symptoms such as rheumatoid factor and anti-citrullinated protein antibodies. They can be correlated with a risk of developing rheumatoid arthritis and can predict more bone erosions and severe disease progression. Biomarkers such as the erythrocyte sedimentation rate and C-reactive protein levels provide information about disease activity, while predictive biomarkers allow clinicians to assess the probability of a treatment response before starting a particular therapy particularly in the era of biological drugs. This move from traditional approaches to patient stratification and targeted treatment should greatly improve patient care and reduce medical costs.

Background: Abatacept acts as a co-stimulation modulator preventing activation of T cells. Although it is approved for the treatment of rheumatoid arthritis (RA), its effects on adaptive immune response have not been fully elucidated. 

Objectives: To observe, in a cohort study, based on a clinical practice setting, the variation of peripheral blood T cells, immunoglobulin levels, and autoantibodies in the serum of RA patients during abatacept therapy. 

Methods: Our study comprised 48 RA patients treated with abatacept. All clinical data were collected at baseline and after 3 months of treatment. Clinical and laboratory tests included erythrocyte sedimentation rate, C-reactive protein, 28-joint disease activity score, RF, anti-citrullinated protein antibody, total immunoglobulins, immunoglobulin A (IgA), immunoglobulin G (IgG), immunoglobulin M (IgM), and lymphocyte sub-population. 

Results: Total immunoglobulin serum levels significantly decreased after 3 months of treatment and correlated positively with disease activity both at baseline and after 3 months of abatacept treatment. A reduction of serum IgM, IgG, IgA and RF was also demonstrated. The absolute number and percentage of cytotoxic (CD8+) T cells significantly decreased after 3 months of abatacept treatment, in particular the percentage of cytotoxic (CD8+) T cells significantly decreased only in patients responding to the treatment.

Conclusions: Our results highlight a different role of abatacept in the modulation of the adaptive immune response in RA by the reduction of polyclonal B-cell activation and cytotoxic T cells. 

 

Hyperbaric oxygen therapy (HBOT) has been investigated as a primary/adjunctive treatment for a number of injuries and medical conditions including traumatic ischemia, necrotizing soft tissue injuries, non-healing ulcers and osteoradionecrosis, but the results are controversial. There is insufficient evidence to support or reject the use of HBOT to quicken healing or to treat the established non-union of fractures. However, in patients with fibromyalgia, HBOT reduces brain activity in the posterior cortex and increases it in the frontal, cingulate, medial temporal and cerebellar cortices, thus leading to beneficial changes in brain areas that are known to function abnormally. Moreover, the amelioration of pain induced by HBOT significantly decreases the consumption of analgesic medications. In addition, HBOT has anti-inflammatory and oxygenatory effects in patients with primary or secondary vasculitis. 

This review analyzes the efficacy and limitations of HBOT in orthopedic and rheumatologic patients.