Predictors of disease activity in gout: a 12-month analysis of the ATTACk (Achieving improvement in the management of crystal-induced arthritis) multicentre cohort study.

OBJECTIVES: Gout treatment is largely suboptimal in clinical practice. We aimed to assess the predictors of disease-activity at 12 months in a real-life setting. METHODS: Consecutive patients referred to Rheumatology Units for suspected acute crystal-induced arthritis were enrolled in a multicentre-cohort study. Only patients with clinical diagnosis of gout were eligible. Disease-activity was evaluated by the Patient Acceptable Symptom State (PASS) on a visual analogue scale (VAS, 0=unsatisfactory, 100=satisfactory) at 0 (T0) and 12 months (T12), and the composite score called Gout Activity Score (GAS) calculated on the number of arthritic attacks (flare count), serum uric acid (sUA), cumulative number of tophi, VAS (T12), PtGA (T12). Multivariate linear regression model was performed to assess predictors of gout disease-activity at T12 with PASS and GAS as outcomes. RESULTS: 201 patients had gout (diagnosis on synovial fluid in 45%, tophi in 26%, mean sUA 7.4±1.9 mg/L, 85% with urate-lowering therapy (ULT) in progress/initiated at T0); mean age 63±13 years, 88% men, median (interquartile range) disease duration 2.9 years (0.7-9.4). Follow-up visits were performed in 113 (56%) patients at T12. Mean PASS observed at T0 and at T12 were 38±27 and 74±23, respectively, whereas GAS at T12 was 10±8. A significant association was observed between the presence of tophi and PASS at T12 (-15.3, 95% CI -25.5, -5.2; p=0.003) and GAS at T12 (+4.0, 95% CI 0.6,7.4; p=0.02), adjusted for age, sex, disease duration, sUA <6 mg/dL, tender joint count, PASS at T0, ULT). CONCLUSIONS: The baseline presence of tophi may predict high disease-activity at T12, thus worsening GAS and patients' pain perception.

Impact of disease duration and gender on the sensitivity and specificity of 2015 ACR/EULAR classification criteria for gout. Cross-sectional results from an Italian multicentric study on the management of crystal-induced arthritis (ATTACk).

OBJECTIVES: We aimed to assess the performance of the 2015 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) gout classification criteria in an Italian cohort of patients with crystal-induced arthritis stratified by disease duration and gender in a real-life setting. METHODS: Consecutive patients referred to Rheumatology Units for suspected acute crystal-induced arthritis were enrolled in a multicentre cohort study by the Italian Society of Rheumatology which was designed to improve the management of crystal-induced arthritis (ATTACk). To test the performance of the criteria (sensitivity and specificity), the presence of monosodium urate (MSU) crystals in synovial fluid (SF) was used as gold standard. Subgroup analyses by gender and disease duration were performed. RESULTS: Two hundred and seventy-seven patients were enrolled. SF analysis was available in 137 (49%) patients. Complete SF analysis and ACR/EULAR scores were obtained in 44% of patients. MSU crystals were found in 66% of patients. The sensitivity and the specificity of all criteria sets were 78% (95%CI, 67-86) and 98% (95%CI, 87-100), respectively; only clinical criteria yielded 70% (95%CI, 59-80) sensitivity and 93% (95%CI, 80-98) specificity, respectively. In early-stage disease (<2 years), the sensitivity dropped to 58% (95%CI, 39-75), while the specificity was 100% (95%CI, 85-100). CONCLUSIONS: The ACR/EULAR criteria showed good performance in patients presenting with acute arthritis; changes were observed when a subset of criteria were used, especially in early-stage disease.

Application of Ultrasound in the Assessment of Oligoarticular Psoriatic Arthritis Subset: Results from Patients Treated with Apremilast.

BACKGROUND: Psoriatic arthritis (PsA) is an inflammatory rheumatic disease characterized by different phenotypes in terms of joint involvement. The so-called oligoarticular pattern involves fewer than five active joints at a different time points. The evaluation of disease activity in this subset of patients is an unmet need due to the lack of specific indices able to capture modifications over time. OBJECTIVES: To evaluate the ability of musculoskeletal ultrasound to monitor the response to apremilast treatment in oligoarticular PsA patients. METHODS: We evaluated 24 oligoarticular patients (19 women, 5 men; median age 56 years, interquartile range (IQR) 19; median disease duration 5 years, IQR 5.75). All patients were assessed at baseline (T0), and after 6 (T1), 12 (T2), and 24 (T3) weeks. Clinical assessment included evaluation of 66 swollen joints and patient global health assessment. All the patients underwent ultrasound assessment of the clinically involved joints. Synovial effusion/hypertrophy and power Doppler were scored with a semi-quantitative scale (0-3). The total inflammatory score was the sum of the scores. RESULTS: We found a reduction in the ultrasound inflammatory score at all time points, with a significant improvement at 6 and 12 weeks of treatment compared with baseline: T0 median 8.5 (IQR 5.0); T1 3.5 (3.0); T2 2.0 (3.5); P = 0.01. We observed a significant reduction of patient global health assessment after 24 weeks (T0 median 50 (32.5); T3 40 (57.5); P = 0.01). CONCLUSIONS: Musculoskeletal ultrasound could be useful in the assessment of treatment response in PsA patients with oligoarticular subset.

Caffeine intake influences disease activity and clinical phenotype in systemic lupus erythematosus patients.

OBJECTIVE: Caffeine, one of the most widely consumed products in the world, seems to interact with multiple components of the immune system by acting as a non-specific phosphodiesterase inhibitor. In vitro dose-dependent treatment with caffeine down-regulates mRNA levels of key inflammation-related genes in peripheral blood mononuclear cells. So far, no robust data are available about the possible contribution of caffeine in systemic lupus erythematosus (SLE). The aim of this study was to evaluate the impact of caffeine consumption on SLE-related disease phenotype and activity, in terms of clinimetric assessment and cytokine serum levels. METHODS: We performed a cross-sectional study, enrolling consecutive patients and reporting their clinical and laboratory data. Disease activity was assessed by SLE Disease Activity Index 2000 (SLEDAI-2K). Caffeine intake was evaluated by a 7-day food frequency questionnaire, including all the main sources of caffeine. As previously reported, patients were divided into four groups according to the daily caffeine intake: <29.1 mg/day (group 1), 29.2-153.7 mg/day (group 2), 153.8-376.5 mg/day (group 3) and >376.6 mg/day (group 4). At the end of questionnaire filling, blood samples were collected from each patient to assess cytokine levels. These were assessed by using a panel by Bio-Plex assays to measure the levels of IL-6, IL-10, IL-17, IL-27, IFNγ, IFNα and BLyS. RESULTS: We enrolled 89 consecutive SLE patients. We observed a negative correlation between caffeine consumption and disease activity, measured with SLEDAI-2K. A significantly higher prevalence of lupus nephritis, neuropsychiatric involvement, haematological manifestations, hypocomplementaemia and anti-dsDNA positivity was observed in patients with a low intake of caffeine. Furthermore, patients with a low intake of caffeine were more frequently treated with glucocorticoids. Regarding cytokine analysis, a negative correlation between daily caffeine consumption and serum level of IFNγ was found (p = 0.03, r = -0.2); furthermore, patients with a high intake of caffeine showed lower serum levels of IFNα (p = 0.02), IL-17 (p = 0.01) and IL-6 (p = 0.003). CONCLUSIONS: In this report we demonstrated the impact of caffeine on SLE disease activity status, as confirmed by the inverse correlation between its intake and both SLEDAI-2K values and cytokine levels. Moreover, patients with a low caffeine consumption seem to have a more severe disease phenotype.

Porphyromonas gingivalis and rheumatoid arthritis.

PURPOSE OF REVIEW: To explore the pathogenic association between periodontal disease and rheumatoid arthritis focusing on the role of Porphyromonas gingivalis. RECENT FINDINGS: In the last decades our knowledge about the pathogenesis of rheumatoid arthritis substantially changed. Several evidences demonstrated that the initial production of autoantibodies is not localized in the joint, rather in other immunological-active sites. A central role seems to be played by periodontal disease, in particular because of the ability of P. gingivalis to induce citrullination, the posttranslational modification leading to the production of anticitrullinated protein/peptide antibodies, the most sensitive and specific rheumatoid arthritis biomarker. SUMMARY: The pathogenic role of P. gingivalis has been demonstrated in mouse models in which arthritis was either triggered or worsened in infected animals. P. gingivalis showed its detrimental role not only by inducing citrullination but also by means of other key mechanisms including induction of NETosis, osteoclastogenesis, and Th17 proinflammatory response leading to bone damage and systemic inflammation.

Periodontitis and Rheumatoid Arthritis: The Same Inflammatory Mediators?

The strict link between periodontitis (PD) and rheumatoid arthritis (RA) has been widely demonstrated by several studies. PD is significantly more frequent in RA patients in comparison with healthy subjects: this prevalence is higher in individuals at the earliest stages of disease and in seropositive patients. This is probably related to the role of P. gingivalis in inducing citrullination and leading to the development of the new antigens. Despite the many studies conducted on this topic, there is very little data available concerning the possibility to use the same biomarkers to evaluate both RA and PD patients. The aim of the review is to summarize this issue. Starting from genetic factors, data from literature demonstrated the association between HLA-DRB1 alleles and PD susceptibility, similar to RA patients; moreover, SE-positive patients showed simultaneously structural damage to the wrist and periodontal sites. Contrasting results are available concerning other genetic polymorphisms. Moreover, the possible role of proinflammatory cytokines, such as TNF and IL6 and autoantibodies, specifically anticyclic citrullinated peptide antibodies, has been examined, suggesting the need to perform further studies to better define this issue.

Insights on the role of physical activity in patients with rheumatoid arthritis.

Patients with rheumatoid arthritis (RA) are physically inactive, and trials have been undertaken to examine the effect of physical activity on pain, disease activity, functional ability and quality of life (QoL) in RA. The aim of this study was to explore the relationship between physical activity and disease-activity in RA and in healthy controls. Our findings showed that fewer RA patients had a professional occupation compared with controls, but patients and controls were similar with respect to the sedentary extent of their job. Physical exercise was inversely associated with disease activity (DAS-28), stiffness visual analog scale (VAS), patient global VAS and SF-36, but not associated with Health Assessment Questionnaire (HAQ), pain VAS, fatigue VAS, global health and the Arthritis Ipact Measurement Scale (AIMS), suggesting that pain and fatigue are important barriers to physical activity. Our findings suggest that this is more pronounced in RA patients who do not participate in regular physical activity, and so physical exercise should be recommended as part of comprehensive RA care.

Self-reported adherence to a home-based exercise program among patients affected by psoriatic arthritis with minimal disease activity.

More than half of all patients with psoriatic arthritis (PsA) exhibit progressive erosive arthritis, associated with severe functional impairment and psychosocial disability. Biologics have been suggested to be more effective in inducing minimal disease activity" (MDA) than disease-modifying antirheumatic drugs (DMARDs). Behavioral patient education appears to be more effective in encouraging patients to increase their physical activity (PA) levels. The aim of the study was to evaluate the benefits of home-based exercises program on disease activity and quality of life in MDA-PsA patients treated with an anti-tumor necrosis factor (TNF) and DMARD therapy. We observed a self-reported adherence rate to home-based exercise of 76.6% and data showed the impact of the exercise program on self-reported health and mental assessment. A positive relationship between patient and therapist is crucial, influencing the quality of the performance, the emotional support, and increasing motivation in PsA patients.

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.

Musculoskeletal ultrasound in monitoring response to apremilast in psoriatic arthritis patients: results from a longitudinal study.

INTRODUCTION/OBJECTIVE: Apremilast, PDE4 competitive inhibitor, has been recently introduced in the treatment of adult psoriatic arthritis (PsA) patients, but only preliminary data are available on imaging evaluation. Thus, we evaluated the response to apremilast in PsA patients by ultrasonographic (US) assessment. METHODS: Thirty-four patients (M/F 7/27; median age 61 years, IQR 15; median disease duration 10 years, IQR 13) treated for polyarticular involvement were longitudinally evaluated. All the patients were assessed at baseline (T0), and after 6 (T1), 12 (T2), and 24 weeks (T3) by DAS28, CDAI, SDAI, and DAPSA. At the same time-points, US assessment was performed in 22 sites (wrists, MCPs, PIPs): synovial effusion/hypertrophy and power Doppler were scored with a semi-quantitative scale (0-3). A total score, corresponding to patient's inflammatory status, was obtained by their sum (0-198). We assessed also the presence of tenosynovitis of flexor tendons of hands' fingers bilaterally, registering the number of involved tendons (US-tenosynovitis score 0-10). RESULTS: We found a significant reduction in the US inflammatory score values after 6 weeks (T0, median 15 (IQR 11.2); T1, 6 (10.0); P = 0.0002), confirmed at T2 (4.0 (4.0), P = 0.0002) and T3 (4.0 (6.0); P = 0.0003). Finally, US-detected tenosynovitis was observed in 44.1% of patients: a significant improvement in tenosynovitis score was identified at 6 weeks (T0, median 4 (IQR 4); T1, 1 (2); P < 0.0001) and maintained at T2 (0 (IQR 1); P < 0.0001) and T3 ((IQR 1.25); P < 0.0001). CONCLUSIONS: Apremilast is able to induce an early and sustained improvement of ultrasonographic inflammatory status at articular and peri-articular level. Key points •Apremilast induces a significant, early, and sustained improvement of inflammatory joint status in psoriatic arthritis patients. •Ultrasonographic assessment is able to monitor articular and peri-articular response to apremilast.

Serological markers associated with disease activity in patients with rheumatoid arthritis treated with rituximab.

OBJECTIVE: To evaluate prospectively serological markers at baseline and during treatment in patients with rheumatoid arthritis (RA) initiating rituximab treatment, following failure of antitumour necrosis factor (TNF)-α therapy. METHODS: Patients with RA and healthy control subjects were recruited. Plasma complement (C)3, C4, rheumatoid factor (RF), anticitrullinated protein antibody (ACPA), immunoglobulin (Ig)M, A and G, disease activity scores (DAS) and therapeutic response were recorded at baseline and at 6, 12 and 18 months. RESULTS: Patients (n = 35) had significantly higher C3 and C4 levels than controls (n = 30). At 12 months after initiation of rituximab, C3 and C4 levels were significantly lower in patients who responded to treatment, compared with nonresponders. There were direct correlations between C3 levels and DAS at 12 months in the study population as a whole, and between IgM levels and DAS in responding patients after 6, 12 and 18 months' treatment. CONCLUSIONS: C3 and IgM levels may represent potentially useful serological markers of disease activity during rituximab treatment in patients with RA.