Long-Term Retention Rate of Tofacitinib in Rheumatoid Arthritis: An Italian Multicenter Retrospective Cohort Study.

Background: Tofacitinib (TOFA) was the first Janus kinase inhibitor (JAKi) to be approved for the treatment of rheumatoid arthritis (RA). However, data on the retention rate of TOFA therapy are still far from definitive. Objective: The goal of this study is to add new real-world data on the TOFA retention rate in a cohort of RA patients followed for a long period of time. Methods: A multicenter retrospective study of RA subjects treated with TOFA as monotherapy or in combination with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) was conducted in 23 Italian tertiary rheumatology centers. The study considered a treatment period of up to 48 months for all included patients. The TOFA retention rate was assessed with the Kaplan-Meier method. Hazard ratios (HRs) for TOFA discontinuation were obtained using Cox regression analysis. Results: We enrolled a total of 213 patients. Data analysis revealed that the TOFA retention rate was 86.5% (95% CI: 81.8-91.5%) at month 12, 78.8% (95% CI: 78.8-85.2%) at month 24, 63.8% (95% CI: 55.1-73.8%) at month 36, and 59.9% (95% CI: 55.1-73.8%) at month 48 after starting treatment. None of the factors analyzed, including the number of previous treatments received, disease activity or duration, presence of rheumatoid factor and/or anti-citrullinated protein antibody, and presence of comorbidities, were predictive of the TOFA retention rate. Safety data were comparable to those reported in the registration studies. Conclusions: TOFA demonstrated a long retention rate in RA in a real-world setting. This result, together with the safety data obtained, underscores that TOFA is a viable alternative for patients who have failed treatment with csDMARD and/or biologic DMARDs (bDMARDs). Further large, long-term observational studies are urgently needed to confirm these results.

Prevalence and real-world management of vedolizumab-associated enthesitis in successfully treated IBD patients.

BACKGROUND: Some studies have reported the development of moderate and severe de novo SpA-associated disease under vedolizumab (VDZ) treatment for IBD. Herein, we report a case series who developed severe enthesitis under VDZ therapy from a cohort of 90 treated cases. METHODS: In a single Italian IBD Unit in which 90 cases were on VDZ therapy, we identified 11 cases who developed severe enthesitis. The onset of disease in relationship to VDZ initiation, clinical and sonographic imaging features, and outcomes (including therapy switches) was described. RESULTS: A total of 11 cases, including 8 prior anti-TNF failures, with new-onset entheseal pathology were identified: multifocal (n = 4), unifocal (n = 6), and enthesitis/synovitis/dactylitis (n = 1). The mean duration of symptoms was 46 weeks (range 6-119), the mean CRP was 5.1 mg/dl, and the majority were HLA-B27 negative and showed good clinical response for gut disease. Clinical features and US showed severe enthesitis, including power Doppler change in 7 patients. All patients were initially treated with NSAIDs, and 5 patients underwent local steroid injections. At 12 months, 5/7 cases continued VDZ and 2 were switched to ustekinumab. At 12 months follow-up of 7 cases, 5 patients were in clinical remission and 2 patients had mild enthesitis with minimal increase of power Doppler signal. In addition, 4/7 severe patients developed marked post-inflammatory entheseal calcifications. CONCLUSIONS: A predominant isolated severe enthesitis pattern of SpA may develop under VDZ therapy with severe disease in 8% of cases. Most cases continued VDZ therapy.

Clinical and sonographic discrimination between fibromyalgia and spondyloarthopathy in inflammatory bowel disease with musculoskeletal pain.

OBJECTIVES: Joint pain is common in subjects with IBD and is linked to several factors including SpA, drug therapy, concomitant OA or FM. The primary aim of this study was to estimate the prevalence of primary FM and concomitant FM and SpA in a cohort of patients with IBD utilizing clinical and US assessment. METHODS: A total of 301 consecutive cases with IBD attending two IBD Units were assessed by a rheumatologist for Assessment of SpondyloArthritis International Society criteria fulfilment for SpA or the 2010 ACR criteria for FM. Some 158 cases also had US entheseal examination on large insertions in the upper and lower limbs. RESULTS: Thirty-seven IBD patients (12%) met the ACR criteria for primary FM with 9% presenting with primary FM and 3.3% presenting with concomitant FM and SpA. Meeting FM criteria was not related to smoking, sedentary job, BMI or the presence of psoriasis. FM patients presented higher Leeds Enthesitis Index, BASDAI and BASFI scores than SpA patients. At US examination, patients who satisfied the Assessment of SpondyloArthritis International Society criteria for SpA had significantly higher mean enthesis or patient power Doppler positive as compared with the IBD and FM group (P < 0.001). CONCLUSION: We found that FM occurred in 12% of SpA patients and in this setting SpA disease activity indices performed poorly. US examination in a large patient subgroup showed a promising discriminating capacity between FM and SpA in IBD patients.

Association between Leeds Dactylitis Index and ultrasonographic features: a multicentre study on psoriatic hand dactylitis.

OBJECTIVES: The aim of this study was to explore the link between specific sonographic findings and Leeds Dactylitis Index basic (LDI-b) score in psoriatic arthritis (PsA) patients with hand dactylitis. METHODS: Ninety-one hand dactylitis were evaluated in a multicentre study for the presence of pain, functional limitation and tenderness (2-point scale) and LDI-b score. Dactylitic fingers were investigated using high-frequency US in grey scale (GS) and power Doppler (PD). According to median LDI-b score value of 12, fingers were then divided into two groups and categorised into quartiles on the basis of the value of ratio of circumference. RESULTS: Dactylitic fingers with a LDI-b score >12 showed a significantly higher prevalence of GS flexor tenosynovitis (p=0.015), PD flexor tenosynovitis (p=0.001) and soft tissue oedema (p=0.004), when compared with those with those with LDI-b score <12. GS synovitis at proximal interphalangeal (PIP) level (p=0.003) showed more frequent in dactylitic fingers with a LDI-b score <12, than those with a higher LDI-b value. Fingers in the fourth quartile showed a significantly higher prevalence of GS flexor tenosynovitis of grade ≥2 (p=0.046) and joint synovitis of grade ≥2 at PIP level (p=0.028). CONCLUSIONS: We found that high values of LDI are associated with US flexor tenosynovitis and soft tissue oedema in PsA dactylitis. Results suggest a potential role of PIP joint synovitis in the genesis of hand digital swelling and of extra-articular structures alterations in determining the LDI score.

Mature CD10+ and immature CD10- neutrophils present in G-CSF-treated donors display opposite effects on T cells.

The identification of discrete neutrophil populations, as well as the characterization of their immunoregulatory properties, is an emerging topic under extensive investigation. In such regard, the presence of circulating CD66b+ neutrophil populations, exerting either immunosuppressive or proinflammatory functions, has been described in several acute and chronic inflammatory conditions. However, due to the lack of specific markers, the precise phenotype and maturation status of these neutrophil populations remain unclear. Herein, we report that CD10, also known as common acute lymphoblastic leukemia antigen, neutral endopeptidase, or enkephalinase, can be used as a marker that, within heterogeneous populations of circulating CD66b+ neutrophils present in inflammatory conditions, clearly distinguishes the mature from the immature ones. Accordingly, we observed that the previously described immunosuppressive neutrophil population that appears in the circulation of granulocyte colony-stimulating factor (G-CSF)-treated donors (GDs) consists of mature CD66b+CD10+ neutrophils displaying an activated phenotype. These neutrophils inhibit proliferation and interferon γ (IFNγ) production by T cells via a CD18-mediated contact-dependent arginase 1 release. By contrast, we found that immature CD66b+CD10- neutrophils, also present in GDs, display an immature morphology, promote T-cell survival, and enhance proliferation and IFNγ production by T cells. Altogether, our findings uncover that in GDs, circulating mature and immature neutrophils, distinguished by their differential CD10 expression, exert opposite immunoregulatory properties. Therefore, CD10 might be used as a phenotypic marker discriminating mature neutrophils from immature neutrophil populations present in patients with acute or chronic inflammatory conditions, as well as facilitating their isolation, to better define their specific immunoregulatory properties.

Observational study on the QUality of life of Italian Axial SpondyloARthritis patients (QUASAR): baseline data.

OBJECTIVES: To describe the baseline characteristics of the patients enrolled in the QUality of life in patients with Axial SpondyloARthritis (QUASAR) study in terms of quality of life (QoL), disease activity, therapy adherence, and work ability in a real-world setting. METHODS: QUASAR is an Italian multicentre, prospective 12-month observational study, including consecutive adult patients classified as axial spondyloarthritis (axSpA) according to the Assessment of SpondyloArthritis international Society criteria for axSpA. RESULTS: Of 512 patients enrolled in 23 rheumatology centres, 80.7% had ankylosing spondylitis (AS) and 19.3% had non-radiographic axSpA (nr-axSpA). Mean ages were 34.1±13.3 years at axSpA symptoms onset and 39.5±13.0 years at diagnosis. Of the patients, 51.4% presented with ≥1 extra articular manifestation (EAM); the most common were psoriasis (17.8%) and uveitis (16.4%). Patients with nr-axSpA and AS had similar EAM rates, disease activity, and QoL. Biologic disease-modifying anti-rheumatic drugs (bDMARDs; 83.2%) were the most commonly received medication, followed by conventional synthetic DMARDs (22.9%) and non-steroidal anti-inflammatory drugs (NSAIDs; 16.6%). At baseline, higher treatment satisfaction was reported with bDMARDs which, together with NSAIDs, were associated with the best overall scores for disease activity, function, and QoL in the overall population and AS subgroup. CONCLUSIONS: QUASAR is the first Italian prospective study that comprehensively evaluated a large axSpA patient sample in a real-world setting. This interim analysis at baseline confirmed that i) patients with AS and nr-axSpA have similar QoL and disease burden, ii) nearly all axSpA patients receive treatment, and iii) bDMARDs and NSAIDs, overall, yield better disease activity and QoL.

'Deep Koebner' phenomenon of the flexor tendon-associated accessory pulleys as a novel factor in tenosynovitis and dactylitis in psoriatic arthritis.

OBJECTIVES: Skin and joint involvement in psoriasis (PsO) and psoriatic arthritis (PsA) are thought to relate to the so-called Koebner response. Given that dactylitis is non-randomly distributed in the digits, this study tested the hypothesis that the accessory pulleys linked to the flexor tendons were thickened in PsA and thus exhibited koebnerisation. METHODS: Ninety-six subjects (27 PsA, 27 rheumatoid arthritis (RA), 23 PsO and 19 healthy controls (HCs)) were enrolled. The A1, A2 and A4 pulley thickness was measured using a high-resolution probe (22 MHz). All patients were in remission or low disease activity with current dactylitis being excluded. RESULTS: Within 864 pulleys investigated, patients with PsA had thicker pulleys in every digit compared with both RA (P<0.001 and P=0.003) and HCs (P<0.001). RA and PsO groups had some pulleys in some digits thicker than HCs whereas some others were comparable. The second digit A1 pulley thickness was higher in patients with PsA with previous dactylitis (P=0.020). More pulleys were thickened in the PsA group (165/243, 68%) than RA (41/243, 17%; P<0.001) and HCs (13/171, 7.6%; P<0.001). CONCLUSIONS: In established PsA, the accessory pulleys are thickened compared with RA, PsO or HCs and especially in subjects with a history of dactylitis. These findings implicate the involvement of pulleys in PsA-related tenosynovitis and dactylitis supporting the idea of deep koebnerisation in dactylitis and sites of high physical stress.

Comprehensive evaluation of finger flexor tendon entheseal soft tissue and bone changes by ultrasound can differentiate psoriatic arthritis and rheumatoid arthritis.

OBJECTIVES: To determine whether a detailed sonographic evaluation of the hand flexor tendon compartment could help differentiate between psoriatic arthritis (PsA) and rheumatoid arthritis (RA). METHODS: Thirty-seven patients with PsA, 47 with RA and 10 healthy controls (HC) had flexor tendon (FT) compartment imaging of the dominant hand 2nd to 4th tendons using grey scale (GS) and power Doppler (PD) ultrasound (US) with evaluation for tenosynovitis, peri-tendinous lesions, soft tissue oedema and bony changes at FT insertions. 24/37 PsA and 19/47 RA cases had morning stiffness and 19/37 PsA and 10/47 RA had swollen and/or tender fingers. RESULTS: Tenosynovitis was more common in PsA (25/37) despite higher DAS28 scores in RA (25/37 versus 10/45; p<0.001). Peri-tendinous dermal soft tissue oedema with associated PD signal was evident in one third of PsA patients but in no RA patients (p=0.003). Flexor tendon enthesopathy including new bone formation at the insertional site was significantly more common in PsA (p=0.001). Considering a total inflammatory score per patient summing up the three modifications of the flexor tendon (tenosynovitis, peri-tendinous oedema and insertional enthesophytes) the difference between PsA and RA remained statistically significant (p<0.001). CONCLUSIONS: Our study adds to the growing body of literature that high resolution US of the hand FT compartment may help differentiate between RA and PsA, which needs assessment in the diagnostic setting.

Influence of Safety Warnings on the Prescribing Attitude of JAK Inhibitors for Rheumatoid Arthritis in Italy.

Background/Objectives: The Janus kinase inhibitors (JAKi) tofacitinib (TOFA), baricitinib (BARI), upadacitinib (UPA), and filgotinib (FILGO) are effective drugs for the treatment of rheumatoid arthritis. However, the US Food and Drug Administration (FDA) raised concerns about the safety of TOFA after its approval. This prompted the European Medicines Agency (EMA) to issue two safety warnings for limiting TOFA use, then extended a third warning to all JAKi in patients at high risk of developing serious adverse effects (SAE). These include thrombosis, major adverse cardiac events (MACE), and cancer. The purpose of this work was to analyze how the first two safety warnings from the EMA affected the prescribing of JAKi by rheumatologists in Italy. Methods: All patients with rheumatoid arthritis who had been prescribed JAKi for the first time in a 36-month period from 1 July 2019, to 30 June 2022 were considered. Data were obtained from the medical records of 29 Italian tertiary referral rheumatology centers. Patients were divided into three groups of 4 months each, depending on whether the JAKi prescription had occurred before the EMA's first safety alert (1 July-31 October 2019, Group 1), between the first and second alerts (1 November 2019-29 February 2020, Group 2), or between the second and third alerts (1 March 2021-30 June 2021, Group 3). The percentages and absolute changes in the patients prescribed the individual JAKi were analyzed. Differences among the three groups of patients regarding demographic and clinical characteristics were also assessed. Results: A total of 864 patients were prescribed a JAKi during the entire period considered. Of these, 343 were identified in Group 1, 233 in Group 2, and 288 in Group 3. An absolute reduction of 32% was observed in the number of patients prescribed a JAKi between Group 1 and Group 2 and 16% between Group 1 and Group 3. In contrast, there was a 19% increase in the prescription of a JAKi in patients between Group 2 and Group 3. In the first group, BARI was the most prescribed drug (227 prescriptions, 66.2% of the total), followed by TOFA (115, 33.5%) and UPA (1, 0.3%). In the second group, the most prescribed JAKi was BARI (147, 63.1%), followed by TOFA (65, 27.9%) and UPA (33, 11.5%). In the third group, BARI was still the most prescribed JAKi (104 prescriptions, 36.1%), followed by UPA (89, 30.9%), FILGO (89, 21.5%), and TOFA (33, 11.5%). The number of patients prescribed TOFA decreased significantly between Group 1 and Group 2 and between Group 2 and Group 3 (p ˂ 0.01). The number of patients who were prescribed BARI decreased significantly between Group 1 and Group 2 and between Group 2 and Group 3 (p ˂ 0.01). In contrast, the number of patients prescribed UPA increased between Group 2 and Group 3 (p ˂ 0.01). Conclusions: These data suggest that the warnings issued for TOFA were followed by a reduction in total JAKi prescriptions. However, the more selective JAKi (UPA and FILGO) were perceived by prescribers as favorable in terms of the risk/benefit ratio, and their use gradually increased at the expense of the other molecules.

Multicenter observational study on the efficacy of selective Janus Kinase-1 inhibitor upatacitinib in rheumatoid arthritis.

BACKGROUND: Upadacitinib (UPA) is a selective, reversible Janus kinase inhibitor (JAKi) approved for the treatment of RA. However, there is still no solid evidence on the long-term efficacy of UPA in treated patients. The purpose of this study was to determine the efficacy of UPA to obtain remission or low disease activity (LDA) in a series of UPA patients in patients with RA after 6 and 12 months of treatment in a real-world setting. METHODS: A series of 111 consecutive patients treated with UPA in 23 rheumatology centers were enrolled. Personal history, treatment history and disease activity at baseline, after 6 and 12 months were recorded. Intention-to-treat (ITT) and per-protocol (PP) analyses assessed achievement of remission or LDA or defined as DAS28 <2.6 and ≤3.2, respectively. Logistic regression analysis examined the role of several independent factors on the reduction of disease activity after 6 months of treatment. RESULTS: Of the initial group of 111 subjects at baseline, 86 and 29 participants completed clinical assessments at 6 and 12 months. According to ITT analysis, the rates of remission and LDA were 18% and 18% at 6 months and 31.5% and 12.5% at 12 months, respectively. PP analysis showed higher rates of remission and LDA at 6 (23.3% and 19.8%) and 12 months (55.2% and 20.7%). Results of multivariate logistic regression analysis indicated that a low DAS28 score (P=0.045) was the only predictor of achieving remission at 6 months. None of the baseline factors predicted remission/LDA at 6 months. CONCLUSIONS: RA patients treated with UPA achieved a significant rate of disease remission or LDA in a real-world setting. The 6-month response was found to depend only on the baseline value of DAS28, while it was not influenced by other factors such as disease duration, line of treatment or concomitant therapy with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) or corticosteroids.

Predictors of DAPSA Response in Psoriatic Arthritis Patients Treated with Apremilast in a Retrospective Observational Multi-Centric Study.

BACKGROUND: To date, only a few real-world-setting studies evaluated apremilast effectiveness in psoriatic arthritis (PsA). The aims of this retrospective observational study are to report long-term Disease Activity Index for Psoriatic Arthritis (DAPSA) response of apremilast in PsA patients and to analyze the predictors of clinical response. METHODS: All PsA consecutive patients treated with apremilast in fifteen Italian rheumatological referral centers were enrolled. Anamnestic data, treatment history, and PsA disease activity (DAPSA) at baseline, 6 months, and 12 months were recorded. The Mann-Whitney test and chi-squared tests assessed the differences between independent groups, whereas the Wilcoxon matched pairs signed-rank test assessed the differences between dependent samples. Logistic regressions verified if there were factors associated with achievement of DAPSA low disease activity or remission at 6 and 12 months. RESULTS: DAPSA low disease activity or remission rates at 6 and 12 months were observed, respectively, in 42.7% (n = 125) and 54.9% (n = 161) patients. Baseline DAPSA was inversely associated with the odds of achieving low disease activity or remission at 6 months (odds ratio (OR) 0.841, 95% confidence interval (CI) 0.804-0.879; p < 0.01) and at 12 months (OR 0.911, 95% CI 0.883-0.939; p < 0.01). CONCLUSIONS: Almost half of the PsA patients receiving apremilast achieved DAPSA low disease activity or remission at 6 and 12 months. The only factor associated with achievement of low disease activity or remission at both 6 and 12 months was baseline DAPSA.

Therapeutic Effects of Apremilast on Enthesitis and Dactylitis in Real Clinical Setting: An Italian Multicenter Study.

INTRODUCTION: Enthesitis and dactylitis are difficult-to-treat features of psoriatic arthritis (PsA), leading to disability and affecting quality of life. OBJECTIVE: The aim of this study is to evaluate enthesitis (using the Leed enthesitis index (LEI)) and dactylitis at 6 and 12 months in patients treated with apremilast. METHODS: Patients affected by PsA from fifteen Italian rheumatological referral centers were screened. The inclusion criteria were: (a) enthesitis or dactylitisphenotype; (b) treatment with apremilast 30 mg bid. Clinical and treatment history, including PsA disease activity, were recorded. Mann-Whitney and chi-squared tests were used to assess the differences between independent groups, and Wilcoxon matched pairs signed-rank test assessed the differences between dependent samples. A p-value of <0.05 was considered statistically significant. RESULTS: The Eph cohort consisted of 118 patients (median LEI 3); the Dph cohort included 96 patients with a median dactylitis of 1 (IQR 1-2). According to an intention to treat analysis, 25% and 34% of patients with enthesitis achieved remission (i.e., LEI = 0) in T1 and T2. The remission of dactylitis was 47% in T1 and 44% in T2. The per protocol analysis (patients observed for at least 12 months) showed that both dactylitis and LEI significantly improved in T1 (median LEI 1 (IQR 1-3)) and T2 (median LEI 0 (IQR 1-2)). CONCLUSION: Eph and Dph PsA patients treated with apremilast experienced a significant improvement in enthesitis and dactylitis activity. After 1 year, enthesitis and dactylitis remission was achieved in more than one-third of patients.

Adalimumab and ABP 501 in the Treatment of a Large Cohort of Patients with Inflammatory Arthritis: A Real Life Retrospective Analysis.

The recent introduction of ABP 501, an adalimumab biosimilar, in the treatment of rheumatic diseases was supported by a comprehensive comparability exercise with its originator. On the other hand, observational studies comparing adalimumab and ABP 501 in inflammatory arthritis are still lacking. The main aim of this study is to compare the clinical outcomes of the treatment with adalimumab, both the originator and ABP 501, in a large cohort of patients affected by autoimmune arthritis in a real life setting. We retrospectively analysed the baseline characteristics and the retention rate in a cohort of patients who received at least a course of adalimumab (originator or ABP 501) from January 2003 to December 2020. We stratified the study population according to adalimumab use: naive to original (oADA), naive to ABP 501 (bADA) and switched from original to ABP 501 (sADA). The oADA, bADA and sADA groups included, respectively, 724, 129 and 193 patients. In each group, the majority of patients had a diagnosis of rheumatoid arthritis. The total observation period was 9805.6 patient-months. The 18-month retentions rate in oADA, bADA and sADA was, respectively, 81.5%, 84.0% and 88.0% (p > 0.05). The factors influencing the adalimumab retention rate were an axial spondylarthritis diagnosis (Hazard Ratio (HR) 0.70; p = 0.04), switch from oADA to ABP 501 (HR 0.53; p = 0.02) and year of prescription (HR 1.04; p = 0.04). In this retrospective study, patients naive to the adalimumab originator and its biosimilar ABP 501 showed the same retention rate. Patients switching from the originator to biosimilar had a higher retention rate, even though not statistically significant, when compared to naive.

Apremilast retention rate in clinical practice: observations from an Italian multi-center study.

OBJECTIVE: There are few real-world setting studies focused on apremilast effectiveness (i.e., retention rate) in psoriatic arthritis (PsA). The main aim of this retrospective observational study is the assessment of apremilast 3-year retention rate in real-world PsA patients. Moreover, the secondary objective is to report the reasons of apremilast discontinuation and the factors related to treatment persistence. METHODS: In fifteen Italian rheumatological referral centers, all PsA consecutive patients who received apremilast were enrolled. Anamnestic data, treatment history, and PsA disease activity (DAPSA) at baseline were recorded. The Kaplan-Meier curve and the Cox analysis computed the apremilast retention rate and treatment persistence-related risk factors. A p-value < 0.05 was considered statistically significant. RESULTS: The 356 enrolled patients (median age 60 [interquartile range IQR 52-67] yrs; male prevalence 42.7%) median observation period was 17 [IQR 7-34] months (7218 patients-months). The apremilast retention rate at 12, 24, and 36 months was, respectively, 85.6%, 73.6%, and 61.8%. The main discontinuation reasons were secondary inefficacy (34% of interruptions), gastro-intestinal intolerance (24%), and primary inefficacy (19%). Age and oligo-articular phenotype were related to treatment persistence (respectively hazard ratio 0.98 IQR 0.96-0.99; p = 0.048 and 0.54 IQR 0.31-0.95; p = 0.03). CONCLUSION: Almost three-fifths of PsA patients receiving apremilast were still in treatment after 3 years. This study confirmed its effectiveness and safety profile. Apremilast appears as a good treatment choice in all oligo-articular PsA patients and in those ones burdened by relevant comorbidities. Key Points • Apremilast retention rates in this real-life cohort and trials are comparable. • The oligo-articular phenotype is associated with long-lasting treatment (i.e., 3 years). • No different or more prevalent adverse events were observed.

Efficacy and Drug Survival after Switching from Etanercept to the Biosimilar SB4: A Real-Life Long-Term Study.

We evaluated the 3-year drug survival and efficacy of the biosimilar SB4/Benepali in rheumatoid arthritis (RA), psoriatic arthritis (PsA) and ankylosing spondylitis (AS) patients, previously treated with etanercept (ETA). Drug survival rate was calculated using the Kaplan-Meier method and Cox proportional hazard models were developed to examine predictors of SB4 discontinuation. 236 patients (120 RA, 80 PsA and 36 AS), aged 60.7 ± 13.8 years and with an ETA duration of 4.1 ± 3.4 years were included. The 3-year retention rate for SB4 was 94.4%, 88% and 86% in AS, RA and PsA patients, respectively, with no difference between groups. Patients without comorbid disease had higher retention rates vs. patients with comorbid disease (90% vs. 60%, p < 0.0001). Disease activity, as measured by DAS28, DAPSA and BASDAI remained stable over the 3 years. Comorbid disease (hazard ratio; HR: 4.06, p < 0.0001) and HAQ at baseline (HR: 2.42, p = 0.0024) significantly increased the risk of SB4 discontinuation, while previous ETA duration was negatively associated with SB4 discontinuation (HR: 0.97, p = 0.0064). Forty-one (17.4%) patients left the study due to the interruption of the SB4 treatment, 31 (75.6%) discontinued due to inefficacy and 10 (24.4%) due to adverse events. This real-life study confirms the similar efficacy profile of ETA with long-term retention and a good safety profile in inflammatory arthritis patients.

Hand Erosive Osteoarthritis and Distal Interphalangeal Involvement in Psoriatic Arthritis: The Place of Conservative Therapy.

Hand erosive osteoarthritis (HEOA) and Psoriatic Arthritis (PsA) with DIP involvement are common diseases affecting the hand. Both of them evolve with a progressive limitation in grip due to limited range of motion of the affected joints and stenosing tenosynovitis. Pharmacological options currently available (corticosteroids and clodronate or Idrossicloroquine) for the treatment of EHOA are mostly symptomatic and currently there are no effective drugs able to modify the course of the disease. In addition, data on drug effectiveness of PsA with DIP involvement are lacking. Conservative therapy should be considered in order to reduce pain and improve hand functionality. There are many studies debating a wide range of non-pharmacological intervention in the management of HEOA: joint protection program, range of motion and strengthening exercise, hand exercise with electromagnetic therapy, application of heat with paraffin wax or balneotherapy, occupational therapy and education. Concerning conservative treatment strategies to treat PsA, on the contrary, current evidence is still weak. Further research is needed to find the correct place of physical therapy to prevent stiffness and ankylosis due to the vicious circle of inflammation-pain-immobility-rigidity.

Ultrasound Effectiveness of Steroid Injection for hand Psoriatic Dactylitis: Results from a Longitudinal Observational Study.

INTRODUCTION: To assess clinical and ultrasound effectiveness of steroid injection (local treatment, LT) into the digital flexor tendon sheath for the treatment of psoriatic dactylitis compared to systemic treatment (ST) alone. METHODS: In this observational, multicentre, prospective study, 88 cases of symptomatic hand dactylitis were evaluated clinically and sonographically by high-frequency ultrasound (US) probe in both greyscale (GS) and power Doppler (PD). The presence of flexor tenosynovitis (FT), soft tissue oedema (STO), peritendon extensor inflammation and synovitis was assessed (including DACtylitis glObal Sonographic-DACTOS-score) before treatment, at 1-month (T1) and 3-months (T3) follow-up. LT was proposed to all patients. Patients refusing LT were treated with oral NSAIDs. Patients continued the same baseline csDMARDs and/or corticosteroid therapy during the whole follow-up period. US response was defined for DACTOS score < 3 and US remission for DACTOS score = 0. RESULTS: At T3 evaluation the ST group showed a significantly higher persistence (grade > 1) of FT and STO (p < 0.001 for all) and MCP synovitis (p = 0.001). US remission was achieved only in the LT group (at T3 31% vs. 0, p < 0.001). The percentage of patients with DACTOS < 3 was significantly greater in the LT group compared with ST group, at both T1 (49% vs. 5%, p < 0.001) and T3 evaluation (76% vs. 7%, p < 0.001). In multiple conditional logistic regression analysis, the only factor associated with US remission was LT (T3 odds ratio = 41.21, p < 0.001). CONCLUSIONS: US confirmed the effectiveness of steroid injection for dactylitis by demonstrating that it involves the resolution of extra-articular inflammation, in particular FT and STO.

The Impact of the SARS-CoV-2 Outbreak on the Psychological Flexibility and Behaviour of Cancelling Medical Appointments of Italian Patients with Pre-Existing Medical Condition: The "ImpACT-COVID-19 for Patients" Multi-Centre Observational Study.

Psychological distress imposed by the SARS-CoV-2 outbreak particularly affects patients with pre-existing medical conditions, and the progression of their diseases. Patients who fail to keep scheduled medical appointments experience a negative impact on care. The aim of this study is to investigate the psychosocial factors contributing to the cancellation of medical appointments during the pandemic by patients with pre-existing health conditions. Data were collected in eleven Italian hospitals during the last week of lockdown, and one month later. In order to assess the emotional impact of the SARS-CoV-2 outbreak and the subject's degree of psychological flexibility, we developed an ad hoc questionnaire (ImpACT), referring to the Acceptance and Commitment Therapy (ACT) model. The Impact of Event Scale-Revised (IES-R), the Depression, Anxiety and Stress Scale (DASS) and the Cognitive Fusion Questionnaire (CFQ) were also used. Pervasive dysfunctional use of experiential avoidance behaviours (used with the function to avoid thought, emotions, sensations), feelings of loneliness and high post-traumatic stress scores were found to correlate with the fear of COVID-19, increasing the likelihood of cancelling medical appointments. Responding promptly to the information and psychological needs of patients who cancel medical appointments can have positive effects in terms of psychological and physical health.

Ultrasonographic Evidence of Predominance of Acute Extracapsular and Chronic Intrasynovial Patterns in 100 Cases of Psoriatic Hand Dactylitis.

OBJECTIVE: To use ultrasonography to study whether the duration of psoriatic dactylitis was associated with different patterns of extracapsular and synovial-based involvement. METHODS: One hundred cases of hand dactylitis from 85 patients with psoriatic arthritis (PsA) were consecutively enrolled in a multicenter cross-sectional study and divided into 2 groups according to dactylitis duration (shorter or longer than the median: 20 weeks). All dactylitis fingers were investigated using high-frequency ultrasound both in greyscale (GS) and power Doppler (PD), evaluating the presence of flexor tenosynovitis, soft tissue edema, subcutaneous PD signal (PDS), extensor tendon involvement, and joint synovitis. RESULTS: Cases with a shorter dactylitis duration (< 20 weeks) had a significantly higher prevalence of GS flexor tenosynovitis of grade > 2, PD flexor tenosynovitis, soft tissue edema, and subcutaneous PDS (p = 0.001, p < 0.001, p < 0.05, and p = 0.001, respectively). However, the presence of synovitis in GS and PD mode (in both cases at proximal interphalangeal level) was more frequent in patients with longer dactylitis duration (p < 0.001). When detected in the chronic form, flexor tenosynovitis was grade 2 or lower. CONCLUSION: In a large cohort of PsA hand dactylitis, we found a predominant extracapsular inflammation (flexor tenosynovitis and soft tissue edema) in early cases and a high prevalence of joint synovitis at proximal interphalangeal level in the chronic form. However, longitudinal imaging studies are needed to clarify these aspects.

Predominant ultrasonographic extracapsular changes in symptomatic psoriatic dactylitis: results from a multicenter cross-sectional study comparing symptomatic and asymptomatic hand dactylitis.

OBJECTIVE: Despite diffuse digital swelling, dactylitis may sometimes be asymptomatic. The objective of this study was to compare the clinical and ultrasonographic features of symptomatic with asymptomatic psoriatic arthritis (PsA) dactylitis. METHODS: One hundred and twenty-five hand dactylitis were evaluated in a multicenter cross-sectional study for the presence of pain, subjective functional limitation, and tenderness (4-points scale) with the calculation of a Leeds Dactylitis Index (LDI) score. Fingers were subsequently investigated using high-frequency ultrasound (US) both in gray-scale (GS) and power Doppler (PD), for the presence and grading of flexor tenosynovitis, soft tissue edema, subcutaneous PD signal (PDUS), extensor tendon involvement, and joints synovitis. Clinical and US characteristics of symptomatic dactylitic fingers were compared with the asymptomatic dactylitic ones. RESULTS: Symptomatic fingers (n = 80) had a significantly lower dactylitis duration compared to asymptomatic fingers (n = 36) (p < 0.001). Values of LDI, patient VAS-pain, and VAS-functional score were significantly higher in fingers with symptomatic dactylitis (p < 0.001 and p = 0.010, respectively). Symptomatic dactylitis had a higher prevalence of flexor tenosynovitis of grade > 2, soft tissue edema and subcutaneous PDUS signal (p < 0.001). Asymptomatic dactylitis showed a greater prevalence of joint synovitis (both in GS and in PD) than symptomatic dactylitis (p < 0.001). CONCLUSIONS: Digital tenderness and pain are linked to US tenosynovitis of grade > 2 and extra synovial abnormalities and conversely asymptomatic dactylitis is associated with joint-based synovitis.Key Points• Digital tenderness and local pain in psoriatic arthritis dactylitis are strongly associated with flexor tenosynovitis of grade> 2, soft tissue edema, and subcutaneous PD signal.• In psoriatic arthritis, asymptomatic dactylitis showed a greater prevalence of joint synovitis than symptomatic dactylitis.• In psoriatic arthritis, ultrasound inflammatory abnormalities are present in about 70% of cold dactylitis which is linked for disease chronicity.• In psoriatic arthritis, the flexor tendon and adjacent soft tissues play a significant role in symptomatic dactylitis.