Are interferon-gamma release assays reliable to detect tuberculosis infection in patients with rheumatoid arthritis treated with Janus kinase inhibitors?

BACKGROUND: Screening for latent tuberculosis infection is recommended in patients with rheumatoid arthritis (RA) starting Janus kinase inhibitors (Jaki). Interferon (IFN)-gamma release assays (IGRAs) are increasingly used for this purpose. Jaki tend to decrease the levels of IFNs, questioning the reliability of IGRAs during treatment with these drugs. OBJECTIVES: To compare the performance of QuantiFERON-TB Gold Plus (QFT-P) and QFT Gold In-tube (QFT-GIT) in RA patients treated with Jaki. METHODS: RA patients underwent QFT-P and QFT-GIT at baseline (T0), and after 3 (T3) and 12 months (T12) of treatment with Jaki. The agreement between the two tests was calculated. The agreement between IGRAs and tuberculin skin test (TST) or chest radiography at baseline was also determined. The variability of QTF-P results was longitudinally assessed. RESULTS: Twenty-nine RA patients (F/M 23/6; median age/IQR 63/15.5 years; median disease duration/IQR 174/216 months) were enrolled. A perfect agreement was found between QFT-P and QFT-GIT at all times (κ = 1). At T0, no agreement was recorded between IGRAs and TST (κ = -0.08) and between TST and chest radiography (κ = -0.07), a low agreement was found between QFT-P and chest radiography (κ = 0.17). A variation of 33.3% in the results of QFT-P was recorded at T3 vs T0, of 29.4% at T12 vs T0, and of 11.8% at T12 vs T3. The median levels of IFN-γ produced by lymphocytes in response to the mitogen of QFT-P decreased after 3 months followed by an increase after 12 months (not significant). No change in the median number of circulating lymphocytes was documented. Glucocorticoids intake was associated with a higher probability of negative or indeterminate IGRA results at T0 (p<0.0001). CONCLUSION: A response to IGRAs is detectable during treatment with Jaki. However, fluctuations in the results of IGRAs have been observed in the absence of correlation with clinical outcomes, thus challenging their interpretation.

Perceived Disease Activity in Rheumatoid Arthritis: When the Physician's Gender Matters.

BACKGROUND: In rheumatoid arthritis (RA), females usually have a worse prognosis. To date, the influence of physician gender in the evaluation of RA activity is still largely unknown. OBJECTIVES: To investigate the discrepancy in RA disease activity assessment between male and female physicians and to compare patient and evaluator perception of disease activity and global health (GH) status. METHODS: One female and one male rheumatologist evaluated 154 RA patients recording tender and swollen joint count, GH, evaluator global assessment (EGA), and patient global assessment (PGA) disease activity. A third rheumatologist calculated DAS28, CDAI, and SDAI. Difference was evaluated by Wilcoxon test. Physician-patient agreement was assessed by intraclass correlation coefficient. RESULTS: GH, PGA, and DAS28 were higher when recorded by the female examiner. Male EGA was higher than female. Among male patients, PGA was higher when collected by the female examiner. The probability of being judged as having an active disease did not rely on physician gender. The agreement with the physician's evaluation of disease activity was high. PGA values were higher than EGA in both examiners. The physician-patient agreement was moderate for the male examiner and good for the female. The female physician had a higher agreement with both genders. CONCLUSIONS: Subjective measure of disease activity differs between female and male rheumatologists, contributing to a different evaluation of disease activity. Patients have a higher perception of disease activity compared to physicians. The stronger agreement between female physicians and patients may be related to a more emphatic setting established by the female physician.

An exploratory cross-sectional study of subclinical vascular damage in patients with polymyalgia rheumatica.

The aim of the study was to investigate the presence of subclinical vascular damage in polymyalgia rheumatica (PMR). We enrolled PMR patients having major cardiovascular risk factors (MCVRF) and, as controls, patients with MCVRF. All underwent: color Doppler ultrasound to evaluate the common carotid intima-media thickness (IMT), the anterior-posterior abdominal aortic diameter (APAD), and the prevalence of carotid artery stenosis; the cardio-ankle vascular index (CAVI) to measure arterial stiffness together with the ankle-brachial index (ABI) to investigate the presence of lower-extremity peripheral arterial disease. Finally, we measured the serum levels of adipocytokines implicated in vascular dysfunction. As a result, 48 PMR and 56 MCVRF patients were included. An increase of IMT (1.07/0.8-1.2 vs 0.8/0.8-1.05; p = 0.0001), CAVI (8.7/7.8-9.3 vs 7.6/6.9-7.8; p < 0.0001) and APAD values (21.15/18.1-25.6 vs 18/16-22; p = 0.0013) was found in PMR patients with respect to controls. No differences were reported in the prevalence of carotid artery stenosis or ABI values between the two groups. A significant correlation between IMT and CAVI in PMR and MCVRF subjects (r2 = 0.845 and r2 = 0.556, respectively; p < 0.01) was found. Leptin levels (pg/mL; median/25th-75th percentile) were higher in PMR than in MCVRF subjects (145.1/67-398.6 vs 59.5/39.3-194.3; p = 0.04). Serum levels of adiponectin (ng/mL) were higher in PMR patients (15.9/10.65-24.1 vs 6.1/2.8-22.7; p = 0.01), while no difference in serum levels of resistin (ng/mL) was found between PMR and MCVRF subjects (0.37/0.16-0.66 vs 0.26/0.14-1.24). Our study shows an increased subclinical vascular damage in PMR patients compared to those with MCVRF, paving the way for further studies aimed at planning primary cardiovascular prevention in this population.

One-year effectiveness, retention rate, and safety of secukinumab in ankylosing spondylitis and psoriatic arthritis: a real-life multicenter study.

BACKGROUND: Secukinumab (SEC) is effective for ankylosing spondylitis (AS) and psoriatic arthritis (PsA) in randomized trials, but real-life data are lacking. RESEARCH DESIGN AND METHODS: Real-life, prospective observational study on 169 consecutive outpatients at baseline (T0) and at 6 (T6) and 12 months (T12) after starting SEC (39 AS, 23%; 130 PsA, 77%). RESULTS: Significant improvement was seen at T6 and T12 for all clinical variables, including TJC, SJC, ESR, CRP, DAPSA, ASDAS-CRP, and BASDAI, as well as in patient-reported outcomes like VAS-pain. By multivariable regression analysis, in AS patients high BASDAI at T0 correlated with diagnostic delay (R2 = 0.4; p = 0.009) and peripheral joint involvement (R2 = 0.4; p = 0.04). During follow-up, reduction of BASDAI positively correlated with high ESR (R2 = 0.65; p = 0.04). ASDAS-CRP at T0 positively correlated with high ESR (R2 = 0.34; p = 0.004). Reduction of ASDAS-CRP from T0 to T6 correlated with current smoking status (R2 = 0.42; p = 0.003). In PsA patients, reduction of DAPSA score from T0 to T12 is negatively correlated with the presence of metabolic syndrome (R2 = 0.41; p = 0.0025). SEC was well tolerated; 10 patients discontinued treatment for non-severe adverse events. CONCLUSIONS: Secukinumab is effective and safe in patients with AS and PsA in a real-life setting.

Secukinumab may be a valid treatment option in patients with CNS demyelination and concurrent ankylosing spondylitis: Report of two clinical cases.

The therapeutic approach to CNS demyelination associated to ankylosing spondylitis is a complex issue due to the contraindication of TNF inhibitors in demyelinating diseases. Secukinumab, a human IgG1κ monoclonal antibody that binds and inhibits IL-17A, was recently approved for the treatment of ankylosing spondylitis. We report the clinical cases of two patients affected by a CNS demyelinating disease and ankylosing spondylitis who were successfully treated with secukinumab, providing additional evidence of the feasibility of this therapeutic option when the use of TNF inhibitors is discouraged by challenging comorbidities.

Dietary Habits Bursting into the Complex Pathogenesis of Autoimmune Diseases: The Emerging Role of Salt from Experimental and Clinical Studies.

The incidence and prevalence of autoimmune diseases have increased in Western countries over the last years. The pathogenesis of these disorders is multifactorial, with a combination of genetic and environmental factors involved. Since the epidemiological changes cannot be related to genetic background, which did not change significantly in that time, the role of environmental factors has been reconsidered. Among these, dietary habits, and especially an excessive salt, typical of processed foods, has been implicated in the development of autoimmune diseases. In this review, we summarize current evidence, deriving both from experimental models and clinical studies, on the capability of excessive salt intake to exacerbate proinflammatory responses affecting the pathogenesis of immune-mediated diseases. Data on several diseases are presented, including rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis, and Crohn's disease, with many of them supporting a proinflammatory effect of salt. Likewise, a hypertonic microenvironment showed similar effects in experimental models both in vivo and in vitro. However, murine models of spontaneous autoimmune polyneuropathy exposed to high salt diet suggest opposite outcomes. These results dictate the need to further analyse the role of cooking salt in the treatment and prevention of autoimmune diseases, trying to shape a fine tuning between the possible advantages of a restricted salt intake and the changes in circulating metabolites, mediators, and hormones which come along salt consumption and could in turn influence autoimmunity.

Effectiveness of Adalimumab for the Treatment of Psoriatic Arthritis: An Italian Real-Life Retrospective Study.

Background: Few studies have evaluated the effectiveness of adalimumab in the real-life setting in psoriatic arthritis (PsA). Objective: To evaluate the 2-year retention rate of adalimumab in PsA patients. Potential baseline parameters influencing persistence on treatment were also evaluated. Methods: PsA patients from 16 Italian Rheumatology Units treated with adalimumab as first- or second-line biological therapy were retrospectively evaluated. Adalimumab retention rate was evaluated at 12 and 24 months. Logistic regression was used to evaluate the association between predictor variables and adalimumab retention rate. Results: From 424 patients (53.5% male, aged 48.3 ± 12.8 years) who started treatment with adalimumab, 367 (86.6%) maintained treatment for 12 months and 313 (73.8%) for 2 years. At 24-months, Disease Activity in PsA (DAPSA) remission (defined as ≤4) and Low Disease Activity (LDA) (≤14) were achieved in 22.8% and 44.4% of patients, respectively. Adalimumab treatment significantly decreased the number of tender (7.0 ± 5.7 at baseline vs. 2.3 ± 3.5 at 24 months, p < 0.001) and swollen joints (2.7 ± 2.8 at baseline vs. 0.4 ± 0.9 at 24 months, p < 0.001), DAPSA (25.5 ± 10.9 at baseline vs. 11.0 ± 8.4 at 24 months, p < 0.001), PASI (5.3 ± 5.7 at baseline vs. 2.7 ± 2.8 at 24 months, p < 0.001) and CRP (3.8 ± 6.3 at baseline vs. 1.2 ± 1.7 at 24 months, p < 0.001). Among a range of laboratory and clinical variables, only female gender was associated with improved adalimumab persistence at 24 months (OR: 1.98, 95% CI: 1.2-3.2, p = 0.005). Conclusions: Independent of a range of predictor variables, adalimumab was shown to be effective, while maintaining a high retention rate after 2 years in PsA patients.

Validation of the Italian version of proposed GRAPPA flare questionnaire for patients with psoriatic arthritis.

OBJECTIVES: The aim of the present study was to validate an Italian version of the GRAPPA flare instrument to identify patients with psoriatic arthritis (PsA) with a possible disease flare. METHODS: This was a cross-sectional study enrolling consecutively PsA patients classified with CASPAR criteria. Inclusion criteria were: age ≥18 years and stable treatment (at least six months of follow-up) with conventional synthetic or biological DMARDs. The flare questionnaire was administered at baseline and within a two-week interval. Internal consistency of the questionnaire was evaluated with Cronbach's alpha coefficient. Construct validity of flare questionnaire was assessed using the correlation between flare score and disease activity indices, HAQ and serum C-reactive protein. Cohen's κ was performed to assess the agreement level between the patient's perception of flare and the score of the questionnaire. Finally, test-retest was performed to assess the reliability of the instrument. RESULTS: 46 PsA patients were enrolled in this study. Of these, 30.4% reported a status of flare of their disease. The questionnaire was internally consistent (alpha=0.81). Moreover, the questionnaire score correlated with the main disease activity indices (Spearman Rho ranging from 0.30 to 0.66; p<0.01). The score of flare questionnaire showed a moderate agreement with the perception of flare from the patients (Cohen's κ=0.54). Test-retest reliability showed a good intra-class correlation. CONCLUSIONS: This initial validation of the Italian version of the GRAPPA flare instrument was favourable. Our results confirm the utility of this questionnaire in the assessment of flare in PsA.

Polymyalgia rheumatica and diverticular disease: just two distinct age-related disorders or more? Results from a case-control study.

In a previous report of two married cohabiting couples affected by polymyalgia rheumatica (PMR), we noticed that the wife of one couple and both members of the other couple suffered from symptomatic diverticular disease (DD), whose diagnosis was made before the onset of PMR. We investigated whether DD might be a risk factor for the development of PMR. We conducted a case-control study informed on a database containing the prospectively collected medical records of consecutive PMR patients. Among comorbidities, attention was focused on symptomatic DD, provided that the diagnosis had been made by colonoscopy and/or computed tomography scan. As controls, we identified one control per case at random among those matched by age and sex attending the ophthalmic and orthopedic outpatient clinics, as long as a PMR diagnosis had been excluded. A logistic regression model was used, following a multiplicative model, and results were presented as odds ratio (OR) and 95% confidence intervals (95% CI). The most frequent comorbidities in the two groups of patients (121 cases and 121 controls) were chronic coronary artery disease, atrial fibrillation, diabetes mellitus, hypertension, DD, hypercholesterolemia, osteoporosis, chronic obstructive pulmonary disease, gastroesophageal reflux disease, and cholelithiasis. The association between PMR and DD (OR = 4.06; 95% CI: 1.76-9.35) was by far stronger than that found comparing PMR with the other comorbidities. The chronic bowel inflammation induced by dysbiosis in patients with symptomatic DD could be a critical immunopathological mechanism supporting the development or exacerbation of PMR in susceptible individuals.