Application of SLE-DAS to assess subcutaneous belimumab efficacy in a cohort of systemic lupus erythematosus patients.

OBJECTIVES: To assess the efficacy of subcutaneous (sc) belimumab (BLM) by the application of SLE-DAS in a monocentric SLE cohort. METHODS: We evaluated SLE patients treated with sc BLM from March 2019. Disease activity has been assessed by SLEDAI-2k, SLE-DAS and PGA (Physician Global Assessment) in all the established time-points [baseline (T0), after 1 (T1), 3 (T3), 6 (T6) and 12 (T12) months]. Furthermore, we applied and compared the achievement of remission according to SLE-DAS values (SLEDAS ≤2.08 + PDN ≤5mg/daily) and DORIS definition (clinical SLEDAI- 2k=0 + PGA<0.5 + antimalarial treatment, PDN≤5mg/daily, stable immunosuppressive treatment). RESULTS: We enrolled 86 patients [M/F 5/81, median age 48 years (IQR 17.5), median disease duration 166 months (IQR 216)]. At baseline, median values of SLEDA-2k and SLE-DAS were 6 (IQR 4) and 5.77 (IQR 4.33), respectively, and they significantly correlated (r=0.719, CI 95% 0.586-0.815, p<0.0001). Median duration of treatment was 14 months (IQR 20). We found a significant reduction of SLEDAI-2k and SLE-DAS already at T1, maintained in the subsequent time-points (p<0.0001). At T12, a remission state was achieved by 60.4% of patients according to SLE-DAS definition and by 62.3% according to the DORIS definition. Both definitions of remission have demonstrated an agreement of 84%, with a Cohen's kappa equal to 0.6. CONCLUSIONS: In this study we applied SLE-DAS to assess the efficacy of sc BLM, by analysing its over-time changes and by comparing its performance with SLEDAI-2k. Indeed, our results suggest the usefulness of this new activity index in a real-life setting.

Kidney Biopsy and Immuno-Rheumatological Diseases: A Retrospective and Observational Study.

Renal involvement is a common occurrence in patients with immuno-rheumatological diseases (IRDs). Several instances of glomerulonephritis (GN) occur in the setting of IRD and complicate the clinical course of an underlying condition. The aim of this study was to observe the spectrum of nephropathies according to age, kidney function, history of IRD at the time of biopsy, and histopathological kidney diagnosis. We evaluated data relating to 699 consecutive kidney native biopsies (female 52.1%) with a median age of 48 years (IQR 34-62) performed in adult patients collected over 15 years. The study population was divided into three groups: patients with kidney histological findings correlated to underlying IRD (Group 1), patients with kidney histological findings not correlated to underlying IRD (Group 2), and patients with kidney histological findings compatible with "de novo" IRD (absent in personal medical history) (Group 3). Kidney involvement related to IRD was found in 25.2% of patients. Group 1 was mostly represented by lupus nephritis (76.6%), with a younger age than Group 3 (p < 0.001) and by a higher percentage of females than other groups (p < 0.001). Group 3 was the most represented by microscopic polyangiitis (50.8%) when compared with the other two groups (p < 0.001). Acute nephritic syndrome (p < 0.001), acute kidney injury (AKI), and abnormal urinalysis (p < 0.001) were more represented in Group 3 than the other groups. In conclusion, IRDs are characterized by different clinical presentations and heterogeneous histological findings. Kidney biopsy remains fundamental to achieving the correct diagnosis and starting targeted therapy.

Remission in Type 2 Inflammatory Diseases: Current Evidence, Unmet Needs, and Suggestions for Defining Remission in Chronic Rhinosinusitis with Nasal Polyps.

PURPOSE OF REVIEW: The development of biological therapies for type 2 inflammatory diseases raises the possibility of addressing remission in those dis-immune conditions. No consensus exists for a definition of remission in chronic rhinosinusitis with nasal polyps (CRSwNP). This review aims to critically evaluate the published data to provide the basis for defining remission in CRSwNP. RECENT FINDINGS: The published evidence has yet to provide an unequivocal definition on remission in type 2 inflammatory diseases, in part reflecting differences in approaches to diagnosis and follow-up. A multidimensional evaluation is necessary when considering complete remission, including clinical, inflammatory, and histologic criteria, but how to combine or tailor the three perspectives according to disease severity at baseline or timing of assessment of treatment category is yet to reach consensus. We suggest defining remission starting from the approach taken in asthma and eosinophilic esophagitis, that is, including the resolution of symptoms and improvements in objective parameters of disease severity and/or inflammatory activity. Future studies and consensuses should provide validated criteria with cutoffs for the day-to-day definition of remission. The definition of remission in CRSwNP should include the following criteria, to be verified and maintained for a period of ≥ 12 months: absence of symptoms (nasal obstruction, loss of smell, rhinorrhea as the main ones); no impact of symptoms on quality of life; no need of surgery; no chronic or rescue medications (systemic corticosteroids or antibiotics); and recovery of smell function, possibly evaluated by objective test. Assessment of underlying inflammation should also be considered once accurate and feasible biomarkers are available in clinical practice.

Effects of cytotoxic T-lymphocyte-associated protein 4 compared to TNF inhibitors on lipid profile: Results from an observational multicentre rheumatoid arthritis cohort.

AIM: To evaluate the impact of selective cytotoxic T-lymphocyte-associated protein 4 (CTLA-4Ig) compared to tumor necrosis factor inhibitors (TNFi) on cardiovascular (CV) clinical and laboratory outcomes in patients with rheumatoid arthritis (RA). METHODS: We performed a prospective observational multicenter study of RA patients included in the "Cardiovascular Obesity and Rheumatic DISease (CORDIS)" Study Group database, collecting demographic, clinical, and laboratory data of those starting a CTLA-4Ig or TNFi at baseline, 6-month, and 12-month follow-up. RESULTS: Of the 206 RA patients without previous CV events enrolled in the study, 64 received a CTLA-4Ig and 142 a TNFi. The two groups did not differ in age, gender, or smoking habits, and the prevalence of hypertension, diabetes, and metabolic syndrome was similar. Over a follow-up period of 12 months, although no significant differences were found in the disease activity course, we observed that LDL cholesterol levels slightly decreased only in the CTLA-4Ig-treated patients. CONCLUSIONS: Patients treated with both CTLA-4Ig and TNFi did not differ in disease activity response and changes in traditional CV risk factors after 12 months of treatment. However, CTL-A-4Ig treatment is associated with a favorable change in lipid profile at 12-month follow-up.

Older Age, a High Titre of Neutralising Antibodies and Therapy with Conventional DMARDs Are Associated with Protection from Breakthrough Infection in Rheumatoid Arthritis Patients after the Booster Dose of Anti-SARS-CoV-2 Vaccine.

Objectives: We aimed to analyse the incidence and severity of breakthrough infections (BIs) in rheumatoid arthritis (RA) patients after a COronaVIrus Disease 2019 (COVID-19) vaccination booster dose. Methods: We enrolled 194 RA patients and 1002 healthcare workers (HCWs) as controls. Clinical, lifestyle and demographic factors were collected at the time of the third dose, and immunogenicity analyses were carried out in a subgroup of patients at 4-6 weeks after the third dose. Results: BIs were experienced by 42% patients (82/194) with a median time since the last vaccination of 176 days. Older age (>50 years; aHR 0.38, 95% CI: 0.20-0.74), receiving conventional synthetic disease modifying antirheumatic drugs (csDMARDs) (aHR 0.52, 95%CI: 0.30-0.90) and having a titre of neutralising antibodies >20 (aHR 0.36, 95% CI: 0.12-1.07) were identified as protective factors. Conversely, anti-IL6R treatment and anti-CD20 therapy increased BI probability. BIs were mostly pauci-symptomatic, but the hospitalisation incidence was significantly higher than in HCWs (8.5% vs. 0.19%); the main risk factor was anti-CD20 therapy. Conclusions: Being older than 50 years and receiving csDMARDs were shown to be protective factors for BI, whereas anti-IL6R or anti-CD20 therapy increased the risk. Higher neutralising antibody titres were associated with a lower probability of BI. If confirmed in a larger population, the identification of a protective cut-off would allow a personalised risk-benefit therapeutic management of RA patients.

Tapering and discontinuation of glucocorticoids in patients with rheumatoid arthritis treated with tofacitinib.

Although the rapid onset of effect of glucocorticoids (GCs) allows rapid control of rheumatoid arthritis (RA) symptoms, their chronic use may be associated with several adverse events. The 2022 update of EUALR recommendations for the management of patients with RA suggests to reduce and discontinue oral GCs as quickly as possible. Considering GCs as a "bridging therapy" to promptly reduce symptoms and control inflammation, fast-acting drugs such as tofacitinib could allow faster and safer tapering of GCs. The purpose of this pilot study was to evaluate the steroid-sparing effect of adding tofacitinib in patients with RA inadequately responsive to methotrexate taking concomitant GCs. In this open-label pilot study, we enrolled patients with moderate to severe RA on a stable dose of prednisone (5-12.5 mg/day) who started treatment with tofacitinib. After 1 month, in patients who achieved at least a moderate EULAR response (decrease of > 1.2 in DAS28_CRP), GCs was tapered according to a predetermined schedule until complete discontinuation at week 12. Disease activity was assessed after 4, 12, 24 and 48 weeks of treatment. The primary endpoint was the percentage of patients discontinuing GCs after 12 weeks of tofacitinib treatment. We enrolled 30 patients (26 F: 4 M, mean age 60 ± 13 years, mean disease duration 13.2 ± 7.8 years). The primary endpoint was achieved: 9 patients (30%) discontinued GCs at week-12. At week-24, other 12 patients (46%) withdrew GCs. The median prednisone dose decreased from 5 mg/day (interquartile range 5-10 mg) to 2.5 (0-5) mg/day at week 12 and 48 (p < 0.00001 vs baseline). At week 48, 12 out of 30 patients (40%) had discontinued prednisone. The percentage of patients achieving remission or low disease activity increased throughout the follow-up without any difference between patients who discontinued or not the GC. In this cohort of long-standing RA patients treated with tofacitinib, the discontinuation of glucocorticoids was achievable in up to 30% of patients. These results should encourage rheumatologists to consider GCs tapering and discontinuation of GCs, as suggested by the 2022 EULAR recommendations, an achievable goal.

Exercise-induced modulation of Interferon-signature: a therapeutic route toward management of Systemic Lupus Erythematosus.

Systemic Lupus Erythematosus (SLE) is a multisystemic autoimmune disorder characterized by flares-ups/remissions with a complex clinical picture related to disease severity and organ/tissue injury, which, if left untreated, may result in permanent damage. Enhanced fatigue and pain perception, worsened quality of life (QoL) and outcome are constant, albeit symptoms may differ. An aberrant SLE immunoprofiling, note as "interferon (IFN)α-signature", is acknowledged to break immunotolerance. Recently, a deregulated "IFNγ-signature" is suggested to silently precede/trigger IFNα profile before clinical manifestations. IFNα- and IFNγ-over-signaling merge in cytokine/chemokine overexpression exacerbating autoimmunity. Remission achievement and QoL improvement are the main goals. The current therapy (i.e., corticosteroids, immunosuppressants) aims to downregulate immune over-response. Exercise could be a safe treatment due to its ever-emerging ability to shape and re-balance immune system without harmful side-effects; in addition, it improves cardiorespiratory capacity and musculoskeletal strength/power, usually impaired in SLE. Nevertheless, exercise is not yet included in SLE care plans. Furthermore, due to the fear to worsening pain/fatigue, SLE subjects experience kinesiophobia and sedentary lifestyle, worsening physical health. Training SLE patients to exercise is mandatory to fight inactive behavior and ameliorate health. This review aims to focus the attention on the role of exercise as a non-pharmacological therapy in SLE, considering its ability to mitigate IFN-signature and rebalance (auto)immune response. To this purpose, the significance of IFNα- and IFNγ-signaling in SLE etiopathogenesis will be addressed first and discussed thereafter as biotarget of exercise. Comments are addressed on the need to make aware all SLE care professional figures to promote exercise for health patients.

Multicentre case-control study evaluating the safety of anti-SARS-CoV-2 vaccines in a cohort of patients with systemic vasculitis.

OBJECTIVES: Data on the safety of anti-SARS-CoV-2 vaccines in patients with rare rheumatic diseases, such as systemic vasculitis (SV), are limited. The aim of this study was to evaluate the occurrence of a disease flare and the appearance of adverse events (AEs) following administration of anti-SARS-CoV-2 vaccine in a multicentre cohort of patients with SV. METHODS: Patients with SV and healthy controls (HC) from two different Italian rheumatology centres were asked to complete a questionnaire assessing disease flares occurrence, defined as new onset of clinical manifestations related to vasculitis needing an implementation of therapy, and local/systemic AEs appearance following anti SARS-CoV-2 vaccination. RESULTS: 107 patients with SV (57 ANCA-associated) and 107 HC were enrolled. A disease flare occurred in only one patient (0.93%) with microscopic polyangiitis after the first dose of an mRNA vaccine. After both the first and the second vaccine dose administration, no significant differences in AEs between patients with SV and HC were observed; no serious AEs were reported as well. CONCLUSIONS: These data suggest a good risk profile for anti-SARS-CoV-2 vaccine in patients with systemic vasculitis.

Rheumatoid Arthritis from Easy to Complex Disease: From the "2022 GISEA International Symposium".

Rheumatoid Arthritis (RA) is a systemic disease with many different clinical phenotypes. RA could be classified according to disease duration, seropositivity for rheumatoid factor (RF) and/or anti-citrullinated protein antibodies (ACPA), joint subtype, clinical behaviourbehavior and many other subgroups. In this review, we summarize and discuss the multifaceted aspects of RA, focusing on the relationship between autoimmunity status and clinical outcome, achievement of remission and influence on treatment response, from the 2022 International GISEA/OEG Symposium.

Italian recommendations for the assessment of cardiovascular risk in rheumatoid arthritis: a position paper of the Cardiovascular Obesity and Rheumatic DISease (CORDIS) Study Group of the Italian Society for Rheumatology.

OBJECTIVES: Rheumatoid arthritis (RA) patients are at high risk of cardiovascular (CV) events. The aim of this position paper is to provide Italian rheumatologists with an easy, feasible and time-saving CV risk assessment in their daily clinical practice. METHODS: A narrative review of the literature and an assessment of the methodological strength underlying the current evidence on CV risk assessment in patients with RA were performed. The evidence-based results were shared among the members of the steering committee of the CORDIS study group of the Italian Society of Rheumatology. Subsequently, a unanimously agreed-upon algorithm was discussed and finally approved by the experts. RESULTS: RA patients should have their CV profile monitored using the Italian 'Progetto Cuore' chart, according to the current EULAR recommendations for CV risk management, at least every 5 years. In the presence of high disease activity, or a multi-drug failure condition, when prolonged treatment with glucocorticoids and/or NSAIDs is required, or if hypertension, dyslipidaemia, or diabetes mellitus are concomitant, a more stringent CV risk assessment should be considered. When moderate CV risk is documented, patients should undergo intima-media thickening measurement. The condition of high CV risk requires a cardiological evaluation. CONCLUSIONS: This position paper provides five Italian recommendations for CV risk assessment in RA patients. A general and uniform approach to CV risk profiling may be useful to identify those patients who should undertake intensive preventive strategies to improve their CV outcomes.

Clinical Features of Diabetes Mellitus on Rheumatoid Arthritis: Data from the Cardiovascular Obesity and Rheumatic DISease (CORDIS) Study Group.

Rheumatoid arthritis (RA) and diabetes mellitus (DM) are linked by underlying inflammation influencing their development and progression. Nevertheless, the profile of diabetic RA patients and the impact of DM on RA need to be elucidated. This cross-sectional study includes 1523 patients with RA and no episodes of cardiovascular events, followed up in 10 Italian University Rheumatologic Centers between 1 January and 31 December 2019 belonging to the "Cardiovascular Obesity and Rheumatic DISease (CORDIS)" Study Group of the Italian Society of Rheumatology. The demographic and clinical features of DM RA patients were compared to non-diabetic ones evaluating factors associated with increased risk of DM. Overall, 9.3% of the RA patients had DM, and DM type 2 was more common (90.2%). DM patients were significantly older (p < 0.001), more frequently male (p = 0.017), with a significantly higher BMI and mean weight (p < 0.001) compared to non-diabetic patients. DM patients were less likely to be on glucocorticoids (p < 0.001), with a trend towards a more frequent use of b/ts DMARDs (p = 0.08), and demonstrated higher HAQ (p = 0.001). In around 42% of patients (n = 114), DM diagnosis preceded that of RA. Treatment lines were identical in diabetic and non-diabetic RA patients. DM is a comorbidity that may influence RA management and outcome. The association between DM and RA supports the theory of systemic inflammation as a condition underlying the development of both diseases. DM may not have a substantial impact on bDMARDs resistance, although further investigation is required to clarify the implications of biological therapy resistance in RA patients.

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.

Effectiveness of non-medical switch from adalimumab bio-originator to SB5 biosimilar and from ABP501 adalimumab biosimilar to SB5 biosimilar in patients with chronic inflammatory arthropathies: a monocentric observational study.

OBJECTIVES: The use of biosimilars is constantly growing, prompting healthcare payers to encourage the switch to these drugs which are less expensive than the reference bio-originator. While switching from a bio-originator to a biosimilar is supported by increasing evidence, data on the switch between different biosimilars of the same reference product are scant. Our study aimed to evaluate the effectiveness of the non-medical switch both between adalimumab (ADA) bio-originator and SB5 biosimilar and between two different ADA biosimilars in patients with inflammatory chronic arthritis. METHODS: We observed adult patients with a diagnosis of rheumatoid arthritis (RA), psoriatic arthritis (PsA), and axial spondyloarthritis (axSpA) treated with ADA bio-originator or ABP501 ADA biosimilar (Amgevita) who switched to SB5 ADA biosimilar (Imraldi) for administrative/economic reasons. Patients were followed up for 4 months. RESULTS: One hundred and ten patients [33 RA, 40 PsA, 37 axSpA; F:M= 49:61; median age 56 years (25th-75th percentile 48-66)] switched from ADA bio-originator to SB5. After 4 months (T4), we observed a significant reduction of patients in remission/low disease activity (baseline 92.7% vs. T4 80.9%; p=0.009), with a risk of moderate-high disease activity significantly higher after the switch [RR 2.6 (95% IC 1.2 to 5.7), p=0.01]. However, no differences were found in DAS28-CRP, DAPSA, ASDAS-CRP, and BASDAI, while patients with RA and PsA experienced a worsening in the patient global assessment-VAS (p=0.04 and p=0.02, respectively), and in patients with PsA a worsening in HAQ was also observed (p=0.03). Forty patients switched from ABP501 biosimilar to SB5 [12 with RA, 25 with PsA, and 3 with axSpA; F:M=24:16; median age 56 years (25th-75th percentile 44-66)]. After 4 months, no differences in DAS28-CRP and DAPSA nor in the percentage of patients in remission/low disease activity were found compared to baseline. Likewise, no differences were found in patient-reported outcomes (PROs). CONCLUSIONS: Our results provide a reassuring profile of effectiveness when switching from ADA originator to one of its biosimilars and between two different biosimilars. However, the worse outcome in PROs in patients initially treated with the bio-originator addresses the attention to a possible nocebo response, which should encourage comprehensive communication with patients.

Glucocorticoid tapering and associated outcome in patients with newly diagnosed systemic lupus erythematosus: the real-world GULP prospective observational study.

OBJECTIVE: A subanalysis of the multicentre Early Lupus inception cohort was performed to investigate the real-world Glucocorticoids (GCs) Use in newly diagnosed systemic lupus erythematosus (SLE) Patients (GULP). METHODS: Patients starting prednisone (PDN) ≥5 mg/day and concomitant hydroxychloroquine or immunosuppressant within 12 months of SLE classification were enrolled. Core set variables were recorded at baseline and every 6 months, including changes in PDN dose, European Consensus Lupus Activity Measurement (ECLAM) and Systemic Lupus International Collaborating Clinics damage index. Regression models analysed predictors of tapering PDN<5 mg/day at any time and outcomes associated with different patterns of GCs tapering. RESULTS: The GULP study included 127 patients with SLE; 73 (57.5%) tapered and maintained PDN <5 mg/day, and 17 (13.4%) discontinued PDN within a 2-year follow-up. Renal involvement (HR: 0.41; p=0.009) and lower C3 serum levels (HR: 1.04; p=0.025) predicted a lack of PDN tapering below 5 mg/day. High ECLAM scores were associated with a greater probability of increasing PDN dose (OR: 1.6; p=0.004), independently of daily intake. Disease relapse rate did not statistically differ (p=0.706) between patients tapering PDN <5 mg/day (42/99, 42.4%) and those tapering PDN without dropping below 5 mg/day (13/28, 46.4%). Every month on PDN <5 mg/day associated with lower damage accrual (IRR: 0.96; p=0.007), whereas never tapering PDN <5 mg/day associated with a higher risk of developing GC-related damage (OR 5.9; p=0.014). CONCLUSION: Tapering PDN <5 mg/day was achieved and maintained in half of newly diagnosed patients with SLE and may represent a good balance between the need to prevent damage accrual and the risk of disease relapse.

Hepatitis B and C virus infection in patients with Systemic and Cutaneous Lupus Erythematosus.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by a multifactorial etiology. The primary aim of this study was to estimate HCV and HBV infection prevalence in a cohort of SLE and Cutaneous Lupus Erythematosus (CLE). We assessed the frequency of these infections in our cohort and the possible associations with disease clinical/laboratory features and disease activity status. The prevalence of chronic HBV infection was 2.2% in the CLE group, while no HBsAg positive patients were identified in the SLE group. Conversely, the prevalence of anti-HCV positive was 2.2% in the SLE group while no anti-HCV positive patients were identified in the CLE group. We found no significant association between anti-HBc positive status and clinical manifestations or disease activity status in either group of patients. Hemodialysis resulted significantly associated with anti-HBc positivity in SLE. In the present study, we found HBsAg positivity in CLE patients but not in the Systemic form (SLE); conversely, a similar prevalence of anti-HBc antibodies in both groups was observed. A possible protective role exerted by SLE in HBV infection may be hypothesized. A higher frequency of HCV infection in SLE compared to CLE suggests a possible involvement of HCV in some SLE-related clinical and immunological features.

In-Office Needle Arthroscopic Synovial Biopsy Is an Effective Diagnostic Tool in Patients With Inflammatory Arthritis.

Purpose: To assess the utility, safety, and accuracy of in-office needle arthroscopic (IONA) synovial biopsy as a diagnostic tool during treatment of drug-resistant monoarticular inflammatory arthritis of the knee. Methods: Consecutive patients diagnosed with rheumatoid or psoriatic arthritis with treatment-resistant monoarticular knee involvement who underwent in-office needle arthroscopic synovial biopsy were considered for inclusion. The exclusion criteria were any current malignancies or infection. All patients underwent systematic physical and laboratory examination. IONA was undertaken to inspect the macroscopic appearance of the joint, choose the biopsy site, and classify synovial inflammation. Once collected, synovial tissue specimens were examined histologically using the Krenn scoring system. Results: In total, 12 patients (9 male and 3 female, median age 57 [interquartile range {IQR} 8] years, median disease duration 156 [IQR 201] months) affected by psoriatic arthritis (n = 6) or rheumatoid arthritis (n = 6) were included in this study. Median operating time was 12 (IQR 11) minutes. Three biopsies per patient were collected. The success rate of specimen collection was 97%, the median postoperative 0-10 visual analog scale pain score was 2 (IQR 3), and only one minor complication occurred. Conclusions: Knee IONA with synovial biopsy is an effective and well-tolerated procedure that can help clinicians formulate specific treatment strategies in patients with refractory pain in the setting of rheumatoid and psoriatic arthritis. Level of Evidence: IV, Therapeutic case series.

Erosive arthritis in systemic lupus erythematosus: application of cluster analysis.

OBJECTIVES: In the present study, we applied cluster analysis (CA) in SLE patients with joint involvement to identify which disease subset most commonly develops erosive damage. METHODS: We collected clinical and laboratory data of SLE patients with a clinical history of joint involvement (arthritis/arthralgia). Ultrasonographic assessment was performed at level of MCPs and PIPs joints, to identify erosive arthritis, defined as the presence of erosions in at least one joint. Moreover, we detected RF, ACPA anti-CarP, and Dkk1 serum levels. We applied an unsupervised hierarchical CA to identify the aggregation of patients into different subgroups sharing common characteristics in terms of clinical and laboratory phenotypes. RESULTS: CA included 112 SLE patients (M/F 6/106; median age 45 years, IQR 17; median disease duration 96 months, IQR 165). Arthritis was observed in 82 patients (73.2%) and inflammatory arthralgia in 30 (26.8%). US-detected erosive arthritis was observed in 29 patients (25.9%). CA on clinical and laboratory features allowed the identification of four main clusters: in particular erosive arthritis was located in a cluster including renal and neuropsychiatric involvement, serositis, positivity for ACPA, anti-Carp, anti-Sm, anti-RNP, detectable levels of Dkk1. CONCLUSIONS: The application of CA made it possible to better characterise SLE phenotype including erosive arthritis. In particular, feature-driven CA leads to the identification of a more aggressive disease, due to a common pathogenic mechanism.

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.