Similarities and differences between younger and older disease onset patients with newly diagnosed systemic lupus erythematosus.

OBJECTIVES: Several studies show that age at onset has an impact on the clinical-serological presentation, comorbidities and disease course of patients with systemic lupus erythematosus (SLE). We evaluated whether, in patients with recent onset SLE, the age at onset correlates with clinical-serological manifestations and with comorbidities. METHODS: We analysed 171 patients with a SLE diagnosis obtained within 12 months of diagnosis enrolled in the Early Lupus project. Based on the age of onset of the first disease symptom, they were stratified into 2 groups: early onset (18-45 years) and late onset (>45 years). The analysis was replicated by stratifying patients based on age at diagnosis (fulfillment of ACR classification criteria). Each comparison was made at baseline and at 36 months of follow-up. RESULTS: Baseline: patients with late onset displayed comorbidities (hypertension, dyslipidemia and osteoporosis) more frequently than early onset group. 11.4% of late onset patients had a malignancy in medical history, not recorded in the early onset cohort. The two groups differed neither in organ involvement (domain BILAG) nor in disease activity (ECLAM). Patients with early onset showed a disease with signs of higher serologic activity (higher frequency of anti-dsDNA positivity and lower mean C3 and C4 levels) and had malar rash more frequently than the late onset group (36.2% vs. 18.2%, p=0.042). Similar results were obtained by stratifying patients by age of diagnosis (18-45 years and >45 years), except for the higher frequency of discoid rash in the group with age at diagnosis >45 years (18% vs. 6.6%, p=0.045). 36 months: the 2 groups of patients independently of the stratification applied did not differ in the accumulation of damage, but showed a different pattern of 8 organ involvement. Musculoskeletal involvement was more frequent both in the late onset group (18.6% vs. 7.3%, p=0.043) and in the group with age at diagnosis >45 years (20.4% vs. 5.9%, p=0.009) compared to their counterparts, while renal involvement was more frequent in the group with age at diagnosis 18-45 years (21.4% vs. 6.1%, p=0.03).A sub analysis at 36 months on patients without hypertension and osteoporosis at enrollment showed that patients with older age at onset had a higher frequency of these comorbidities, compared to their counterparts. CONCLUSIONS: In our cohort, younger disease SLE onset seems to correlate with a more active immunological profile, while late onset with a higher incidence of comorbidities.

Reliability and Diagnostic Accuracy of Radiography for the Diagnosis of Calcium Pyrophosphate Deposition: Performance of the Novel Definitions Developed by an International Multidisciplinary Working Group.

OBJECTIVE: To assess the reliability and diagnostic accuracy of new radiographic imaging definitions developed by an international multidisciplinary working group for identification of calcium pyrophosphate deposition (CPPD). METHODS: Patients with knee osteoarthritis scheduled for knee replacement were enrolled. Two radiologists and 2 rheumatologists twice assessed radiographic images for presence or absence of CPPD in menisci, hyaline cartilage, tendons, joint capsule, or synovial membrane, using the new definitions. In case of disagreement, a consensus decision was made and considered for the assessment of diagnostic performance. Histologic examination of postsurgical specimens under compensated polarized light microscopy was the reference standard. Prevalence-adjusted bias-adjusted kappa values were used to assess reliability, and diagnostic performance statistics were calculated. RESULTS: Sixty-seven patients were enrolled for the reliability study. The interobserver reliability was substantial in most of the assessed structures when considering all 4 readers (κ range 0.59-0.90), substantial to almost perfect among radiologists (κ range 0.70-0.91), and moderate to almost perfect among rheumatologists (κ range 0.46-0.88). The intraobserver reliability was substantial to almost perfect for all the observers (κ range 0.70-1). Fifty-one patients were included in the accuracy study. Radiography demonstrated an overall specificity of 92% for CPPD, but sensitivity remained low for all sites and for the overall diagnosis (54%). CONCLUSION: The new radiographic definitions of CPPD are highly specific against the gold standard of histologic diagnosis. When the described radiographic findings are present, these definitions allow for a definitive diagnosis of CPPD, rather than other calcium-containing crystal depositions; however, a negative radiographic finding does not exclude the diagnosis.

Factors associated with COVID-19-related death in people with rheumatic diseases: results from the COVID-19 Global Rheumatology Alliance physician-reported registry.

OBJECTIVES: To determine factors associated with COVID-19-related death in people with rheumatic diseases. METHODS: Physician-reported registry of adults with rheumatic disease and confirmed or presumptive COVID-19 (from 24 March to 1 July 2020). The primary outcome was COVID-19-related death. Age, sex, smoking status, comorbidities, rheumatic disease diagnosis, disease activity and medications were included as covariates in multivariable logistic regression models. Analyses were further stratified according to rheumatic disease category. RESULTS: Of 3729 patients (mean age 57 years, 68% female), 390 (10.5%) died. Independent factors associated with COVID-19-related death were age (66-75 years: OR 3.00, 95% CI 2.13 to 4.22; >75 years: 6.18, 4.47 to 8.53; both vs ≤65 years), male sex (1.46, 1.11 to 1.91), hypertension combined with cardiovascular disease (1.89, 1.31 to 2.73), chronic lung disease (1.68, 1.26 to 2.25) and prednisolone-equivalent dosage >10 mg/day (1.69, 1.18 to 2.41; vs no glucocorticoid intake). Moderate/high disease activity (vs remission/low disease activity) was associated with higher odds of death (1.87, 1.27 to 2.77). Rituximab (4.04, 2.32 to 7.03), sulfasalazine (3.60, 1.66 to 7.78), immunosuppressants (azathioprine, cyclophosphamide, ciclosporin, mycophenolate or tacrolimus: 2.22, 1.43 to 3.46) and not receiving any disease-modifying anti-rheumatic drug (DMARD) (2.11, 1.48 to 3.01) were associated with higher odds of death, compared with methotrexate monotherapy. Other synthetic/biological DMARDs were not associated with COVID-19-related death. CONCLUSION: Among people with rheumatic disease, COVID-19-related death was associated with known general factors (older age, male sex and specific comorbidities) and disease-specific factors (disease activity and specific medications). The association with moderate/high disease activity highlights the importance of adequate disease control with DMARDs, preferably without increasing glucocorticoid dosages. Caution may be required with rituximab, sulfasalazine and some immunosuppressants.

Non-adherence and discontinuation rate for oral and parenteral methotrexate: A retrospective-cohort study in 8,952 patients with psoriatic arthritis.

BACKGROUND AND AIMS: Treatment options for PsA, following non-steroidal anti-inflammatory drugs (NSAIDs), include conventional synthetic disease modifying anti-rheumatic drugs (csDMARDS), particularly methotrexate (MTX). The present study was performed to determine the non-adherence and discontinuation rates of different methotrexate (MTX) formulations in psoriatic arthritis (PsA). APPROACH AND RESULTS: We performed a retrospective-cohort study on patients with PsA identified by disease-specific code in the administrative-health-databases of a Northern Italian region (Lombardy) between 2004 and 2015. Subjects were defined as non-adherent if less than 80% of the prescribed MTX dose was taken based on the time between each prescription. Discontinuation rates were calculated using the time between the first and the last MTX prescription over an observation period of 120 months. Among 8952 patients with PsA, 33% were treated with MTX (mean dosage 10 mg/week ± 2.5 mg standard deviation), more frequently (59%) in its parenteral formulation at a 10 mg weekly dosage (35%). Oral glucocorticoids were prescribed to 21% of patients, while non-steroidal anti-inflammatory drugs to 45%. Approximately 37% of patients with PsA were defined as non-adherent to MTX, with the oral formulation associated with an increased risk of non-adherence (hazard ratio 2.08, 95% confidence interval 1.84-2.35, p < 0.001) compared with parenteral 10-15 mg weekly doses. Oral MTX was discontinued in 52% of cases without a significantly increased risk of discontinuation compared to parenteral formulations which, at higher dosages, had a more favorable retention rate. CONCLUSION: Oral MTX formulation is associated with a 2-fold risk of non-adherence compared to MTX parenteral route in PsA.

Risk of hospitalization for heart failure in rheumatoid arthritis patients treated with etanercept and abatacept.

To estimate biologic influence on heart failure (HF) risk in rheumatoid arthritis. Retrospective cohort (RECORD Study of Italian Society for Rheumatology) study on administrative healthcare databases. We identified 2527 patients treated with either etanercept (n = 1690) or abatacept (n = 837). HF incidence rate was higher in the abatacept cohort than in the etanercept cohort with a 2.38 (95% CI 1.08-5.27) crude competing risk HR (SHR) for abatacept of developing HF, not confirmed after adjustment for prespecified confounders (SHR 1.43; 95% CI 0.51-3.98). Abatacept, compared to etanercept, is prescribed to patients with a worse cardiovascular profile but does not increase the risk of developing HF, when confounding factors are accounted for.

Sex Differences in the Treatment of Psoriatic Arthritis: A Systematic Literature Review.

Psoriatic arthritis (PsA) is a chronic inflammatory condition associated with skin psoriasis and manifests a wide clinical phenotype, with proposed differences between sexes. Current treatments are based on traditional disease-modifying anti-rheumatic drugs (DMARD), and biologic agents and studies have reported different clinical response patterns depending on sex factors. We aimed to identify sex differences in drug retention rate in patients with PsA and performed a systematic research on MEDLINE, EMBASE and Cochrane databases (1979 to June 2015) for studies regarding effectiveness (measured as drug retention rate) in PsA in both traditional DMARDs and biologics. Demographic data as well as retention rates between sexes were extracted. From a total 709 retrieved references, we included 9 articles for the final analysis. Only one study reported data regarding DMARDs, while eight studies reported retention rate for anti-tumor necrosis factor (TNF) biologics, mainly infliximab, adalimumab and etanercept. No differences were reported in retention rates between sexes for methotrexate, while women manifested lower retention rates compared to men with regard to anti-TNF. We highlight the need to include sex differences in the management flow chart of patients with PsA.

Diagnostic accuracy of ultrasound, conventional radiography and synovial fluid analysis in the diagnosis of calcium pyrophosphate dihydrate crystal deposition disease.

OBJECTIVES: To assess the diagnostic performance of ultrasound (US), x-rays, and microscopic analysis of synovial fluid (SF) for calcium pyrophosphate dihydrate crystal deposition disease (CPPD) using histology as a reference standard. METHODS: We enrolled consecutive patients with osteoarthritis waiting to undergo knee replacement surgery. Each patient underwent US of the knee, focusing on menisci and the hyaline cartilage, the day before surgery. During surgery, SF, menisci and condyles were retrieved and examined microscopically. For the meniscus and cartilage microscopic analysis, 8 samples were collected from each specimen and knee radiographs, performed up to 3 months before surgery, were also assessed. A dichotomous score was given for the presence/absence of CPP for each method. Microscopic findings of the specimens were considered the reference standard. All the procedures followed were in accordance with the ethical standards of the local responsible committee. RESULTS: 42 patients (14 males) were enrolled. All patients underwent US, 34 had eligible radiographs and 32 had SF analysis. 25 patients (59.5%) were positive for CPP at US, 15 (44.1%) at X-ray and 14 (43.7%) at SF. Sensitivity and specificity values were 96% and 87% for US, 75% and 93% for radiography and 77% and 100% for SF respectively. There were no statistically significant differences between the diagnostic performance across single tests. CONCLUSIONS: US proved to be at least as accurate as SF analysis for the diagnosis of CPPD. US, which is feasible and harmless, could be considered the first exam of choice for CPPD diagnosis.

Biomarkers in psoriatic arthritis: a systematic literature review.

Psoriatic arthritis (PsA) is characterized by chronic inflammation of peripheral joints and axial skeleton, associated with a strong genetic background. Clinics include enthesitis or dactylitis and extra-articular involvement as uveitis or inflammatory bowel disease, while treatment options range from nonsteroidal anti-inflammatory drugs (NSAIDs) to biologics, targeting TNF α or Th17. No serum autoantibody is associated with PsA, while other biomarkers have been proposed for early diagnosis or to predict treatment response. To better discuss this area of growing interest we performed a systematic review of the literature on biomarkers in PsA. Our research retrieved 408 papers, and 38 were included in the analysis. Based on the available literature, we draw some recommendations for the use of biomarkers in the management of patients with PsA.

Serum antinuclear and extractable nuclear antigen antibody prevalence and associated morbidity and mortality in the general population over 15 years.

The prevalence of ANA and anti-ENA in the general population is not well established, especially their clinical significance in healthy subjects. We herein determined the prevalence and predictive value of serum ANA and anti-ENA for connective tissue diseases (CTD), cancer, and mortality. We took advantage of a randomly selected sample of the 1998 general population (Isola I) consisting of 2828 subjects (53% women, age 43±13 years) from a well-defined Northern Italian area. Serum ANA and anti-ENA were tested on the 2690 samples available in 2012 (Isola II, 50% women, age 58±13 years). Administrative databases were searched for CTD, cancer diagnosis, and death cases occurring between enrollment and December 31, 2013. The hazard ratio (HR) was calculated for incident cases. Serum ANA is positive in 18.1% for any titer and 6.1% for titers ≥1:160, 23% in subjects over 50 years and 13.1% and 6.1% for any titer and titers ≥1:160, respectively, in women. The HR for CTD development was significantly high for all ANA titers, with the highest for ANA ≥1:160 (HR 14.19, 95% CI 3.07-65.68). ANA positivity was not associated with cancer (HR 1.03; 95% CI 0.75-1.43), or with mortality (HR adjusted for age and sex 1.40; 95% CI 0.94-2.09). Serum anti-ENA is positive in a minority of subjects with highest figures for anti-nucleosome (1.9%), -histone (1.6%) and -PM/Scl (1.5%). In conclusion, serum ANA prevalence in the general population is highest in senior subjects and in women, while the female predominance is significantly lower compared to overt CTD. Serum ANA is associated with an increased probability of CTD development over time, but does not influence survival or cancer risk.

Drug survival of the first course of anti-TNF agents in patients with rheumatoid arthritis and seronegative spondyloarthritis: analysis from the MonitorNet database.

OBJECTIVES: To compare drug survival of different anti-TNF drugs (infliximab, INF, etanercept, ETA, and adalimumab, ADA) in rheumatoid arthritis (RA) and spondyloarthritis (SpA) by analysing data collected from an Italian multicenter observational cohort study. METHODS: All patients with RA or SpA registered in the MonitorNet database who started their first course of anti-TNF therapy were included. Overall drug survival was measured, along with specific reasons of discontinuation (inefficacy or adverse events). A first set of analyses using RA as reference category assessed the relationship between diagnosis and drug survival. A second set of analyses stratified by diagnosis (RA and SpA) used INF as reference drug. Adjustment for confounders was performed. The results are presented as adjusted hazard ratios (adjHR) and 95% confidence intervals (95%CI). RESULTS: 2640 RA patients and 1220 SpA patients with a median follow-up of 17 months (IQR 7.2-33.4) were included in the analyses. Patients with a diagnosis of SpA showed a lower risk of drug discontinuation with an adjHR (95%CI) of 0.81 (0.73, 0.90). In SpA, the subset of patients with ankylosing spondylitis (AS) showed the best survival on treatment. In RA, both ETA and ADA showed a significantly lower probability of withdrawal when compared to INF [adjHR (95%CI) 0.46 (0.38, 0.56) and 0.68 (0.57, 0.81), respectively]. Similar results were found in SpA. CONCLUSIONS: Drug survival for SpA is longer than that in RA mainly due to the AS subgroup. In both RA and SpA, ETA and ADA showed a better retention on treatment when compared to INF.