Effects of upadacitinib on enthesitis in patients with psoriatic arthritis: a post hoc analysis of SELECT-PsA 1 and 2 trials.

OBJECTIVES: To characterize the effect of upadacitinib 15 mg once daily (UPA15) on enthesitis in patients with PsA from the SELECT-PsA Phase 3 trials. METHODS: Patients with an inadequate response/intolerance to one or more non-biologic DMARD (SELECT-PsA 1) or one or more biologic DMARD (SELECT-PsA 2) received UPA15, adalimumab 40 mg every other week or placebo (weeks 0-24) switched to UPA15 (week 24 onward). The Leeds Enthesitis Index (LEI) and Spondyloarthritis Research Consortium of Canada (SPARCC) index were used to assess improvement in enthesitis, enthesitis resolution, maintenance of enthesitis resolution and protection from enthesitis development through week 56. RESULTS: Data from 639 patients receiving UPA15 and 635 patients receiving placebo (including 317 patients who switched from placebo to UPA15) were analysed. UPA15 led to higher rates of enthesitis resolution vs placebo at week 24 (LEI: 59.8% vs 38.0%; SPARCC index: 50.6% vs 31.5%, respectively) and greater improvements in the LEI (-1.7 vs -1.0) and SPARCC index (-3.4 vs -1.9); improvements were maintained through week 56. Improvements were observed after 12 weeks of UPA15 treatment. Over 90% of patients without enthesitis (LEI = 0) at baseline receiving UPA15 were enthesitis-free at week 56, and UPA15 prevented recurrence of enthesitis at week 56 in >80% of patients with enthesitis at baseline who achieved resolution (LEI = 0) at week 24. CONCLUSIONS: UPA15 is associated with a comprehensive improvement in enthesitis, with improvements observed after 12 weeks of treatment. Additionally, treatment with UPA15 was associated with maintaining an enthesitis-free state after resolution and protection against new-onset enthesitis. TRIAL REGISTRATION: ClinicalTrials.gov identifiers: NCT03104400 (SELECT-PsA 1) and NCT03104374 (SELECT-PsA 2).

Age at diagnosis influences the clinical phenotype, treatment strategies and outcomes in patients with giant cell arteritis: results from the observational GCAGE study on a large cohort of 1004 patients.

BACKGROUND: Immune and vascular ageing are proposed risk factors for giant cell arteritis (GCA). Data on the impact of age at diagnosis of GCA on the clinical presentation and course of the disease are scarce. METHODS: Patients with GCA followed at referral centres within the Italian Society of Rheumatology Vasculitis Study Group were enrolled up to November 2021. Patients were grouped according to age at diagnosis: ≤64, 65-79 and ≥80 years old. RESULTS: The study included 1004 patients, mean age 72.1±8.4, female 70.82%. Median follow-up duration was 49 (IQR 23-91) months. Patients in the oldest group (≥80 years) had significantly more cranial symptoms, ischaemic complications and risk for blindness compared with the groups 65-79 and ≤64 years (blindness: 36.98% vs 18.21% vs 6.19%; p<0.0001). Large-vessel-GCA was more frequent in the youngest group (65% of patients). Relapses occurred in 47% of patients. Age did not influence the time to first relapse, nor the number of relapses. Older age was negatively associated with the number of adjunctive immunosuppressants. Patients >65 years old had 2-3 fold increased risk for aortic aneurysm/dissection up to 60 months follow-up. Serious infections, but not other treatment-related complications (hypertension, diabetes, osteoporotic fractures), were significantly associated with older age. Mortality occurred in 5.8% of the population with age >65, cranial and systemic symptoms as independent risk factors. CONCLUSIONS: The highest risk of ischaemic complications, aneurysm development, serious infections and the possible undertreatment make of GCA a very challenging disease in the oldest patients.

Interstitial lung disease in microscopic polyangiitis and granulomatosis with polyangiitis: demographic, clinical, serological and radiological features of an Italian cohort from the Italian Society for Rheumatology.

OBJECTIVES: Interstitial lung disease (ILD) has been described as a possible pulmonary involvement in antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitides (AAV), mainly granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA). Aim of this cross-sectional Italian national study was to describe demographic, clinical and serological profile of ILD related to MPA and GPA and investigate possible correlations between radiologic patterns of ILD and vasculitis features. METHODS: We enrolled 95 consecutive patients with AAV-ILD, 56 affected by MPA (58.9%) and 39 by GPA (41.1%). RESULTS: NSIP was the most frequently detected ILD pattern, observed in c-ANCA patients in 60.9% of cases, followed by UIP pattern mainly observed in p-ANCA patients (47.7%, p=0.03). ILD represented the first clinical manifestation, preceding vasculitis diagnosis in 22.1% of cases and, globally, ILD was already detectable at AAV diagnosis in 66.3% of patients. The diagnosis of ILD preceded that of AAV in 85.7% of p-ANCA positive-patients, while only one patient with c-ANCA developed ILD before AAV (p= 0.039). Multivariate analysis confirmed the correlation of UIP pattern with p-ANCA-positivity and a diagnosis of ILD before AAV, also when adjusted for age and sex. CONCLUSIONS: Our study confirms that UIP is a frequent pattern of lung disease in AAVILD patients. Our results also suggest that ILD can represent an early complication of AAV but also occur in the course of the disease, suggesting the need of a careful evaluation by both pulmonologist and rheumatologist to achieve an early diagnosis. Further prospective studies are needed to define ILD prevalence and evolution in AAV patients.

Quality of life and therapeutic management of axial spondyloarthritis patients in Italy: a 12-month prospective observational study.

OBJECTIVES: To evaluate the health-related quality of life (HRQoL), disease activity, treatment adherence, and work ability in the real-world setting in patients with axial spondyloarthritis (axSpA). METHODS: QUASAR was a prospective 12-month, observational study involving 23 rheumatology centres across Italy, including adult patients with axSpA according to the Assessment of SpondyloArthritis International Society (ASAS) criteria. Patients were followed at baseline, 3, 6, and 12 months for disease activity and health-related QoL (HRQoL), treatment adherence and work ability. Regression analysis was used to assess the association between treatment and outcome variables. RESULTS: 413 (80.7%) out of axSpA 512 patients were diagnosed with ankylosing spondylitis (AS) and 99 (19.3%) with non-radiographic axSpA (nr-axSpA). Nr-axSpA and AS patients had similar baseline disease activity and HRQoL. Biologic disease-modifying anti-rheumatic drugs (bDMARDs) were the most frequent medication (n=426, 83.2%). Over the 1-year follow-up, disease activity measures (joint pain and swelling, CRP, global assessment, BASDAI, ASDAS), HRQoL and work ability significantly improved, while few differences emerged between nr-axSpA and AS patients. Treatment satisfaction and adherence questionnaires improved over the 12 months. Patients treated with bDMARDs showed improved outcomes for disease activity measures and HRQoL variables, greater benefit observed in patients with AS. CONCLUSIONS: We found clinical and HRQoL improvement over 1 year in a large, real-world population of nr-axSpA and AS patients treated with bDMARDs or conventional synthetic DMARDs.

The Nocebo Effect in Rheumatology: An Unexplored Issue.

BACKGROUND: We describe the features of nocebo, and its impact in studies of transition from the originator to the respective biosimilar in inflammatory rheumatic diseases. Investigations in healthy volunteers as well as in the neurology and anesthesiology fields demonstrated the involved cerebral areas and the neurotransmitter pathways responsible for the nocebo response. Whether these findings are applicable to patients with inflammatory rheumatic diseases remains to be demonstrated. Nocebo may account for part of the after-switching biosimilar failures. However, in the absence of validated classification or diagnostic criteria, specific neurochemical and neuroimaging studies, the lack of data on serum tumor necrosis factor and drug levels, and the disease improvement after the switching back to the originator biologic observed in some patients, the nocebo diagnosis remains the role of the individual clinician. Investigations on nocebo pathophysiology and diagnosis are required to address its impact in after-transition biosimilar studies in rheumatology.

Radiologist-rheumatologist multidisciplinary approach in the management of axial spondyloarthritis: a Delphi consensus statement.

OBJECTIVES: The aim of this study was to develop a Delphi consensus statement between rheumatologists and radiologists for the diagnosis and monitoring of axial spondyloarthritis (axial-SpA). METHODS: Following an extensive literature search to identify unmet needs and potential goals for a multidisciplinary approach, a scientific board comprising 28 Italian hospital-based rheumatologists (n=19) and radiologists (n=9) identified 8 "starting points", resulting in the development of 23 consensus statements covering issues from current practice guidelines to specific MRI protocols for the assessment of axial-SpA. Each participant anonymously expressed a level of agreement for each statement using a 5-point Likert scale (1="strongly disagree"; 5="strongly agree") via an online Delphi method.Total cumulative agreement (TCA) was defined as the sum of the percentage of response to items 4 ("agree") and 5 ("absolutely agree"). Consensus was defined as ≥80% total cumulative agreement for each statement. RESULTS: After the first round of voting (28 participants), positive consensus was reached for 28/31 (90.3%) statements. Statements without consensus (n=3) were discussed in a face-to-face plenary session prior to the second vote (28 participants). After the second round voting, positive consensus was attained for all 31 statements, with mean final TCA of 95.5% (range 82.1-100%). CONCLUSIONS: This Delphi consensus statement provides an aid to rheumatologists and radiologists for the diagnosis and monitoring of axial-SpA.

Epidemiology of Psoriasis and Psoriatic Arthritis in Italy-a Systematic Review.

PURPOSE OF REVIEW: Understanding prevalence of diseases within specific regions of a country is important for optimal allocation of healthcare resources/funds. We performed a systematic review to obtain a clearer picture of the epidemiology of psoriasis and psoriatic arthritis across and within specific regions of Italy. RECENT FINDINGS: Prevalence of psoriasis in specific regions showed more variability (0.8-4.5%) than that in the total population (1.8-3.1%). Prevalence of psoriatic arthritis in the general population was reported for only two regions, Chiavari (0.09%) and Marche (0.42%). All other studies reported prevalence of psoriatic arthritis in patients with psoriasis in single centres and Italy-wide (4.7-47.1%). Prevalence of psoriatic arthritis was highest in patients with nail and/or scalp psoriasis and/or intergluteal/perianal region involvement. Based on current available data, these conditions appear to affect a substantial number of people and will likely have an important impact on the Italian healthcare system.

A national survey on the management of psoriatic arthritis using the Delphi method.

OBJECTIVES: Accurate diagnosis and appropriate management of psoriatic arthritis (PsA) is essential to avoid unnecessary morbidity. Our aim in this study was to evaluate the current approach to the management of PsA among rheumatologists. METHODS: A 16-item online questionnaire, produced using the Delphi method, was submitted to a panel of rheumatologists who anonymously expressed their opinions on a scale from 1 (maximum disagreement) to 5 (maximum agreement). Positive consensus was defined by ≥66% of the respondents scoring an item 3, 4 or 5. Negative consensus was defined by ≥66% of the respondents scoring an item 1 or 2. RESULTS: The surveyed rheumatologists agreed that in its early stage, PsA is characterised by the involvement of few joints and/or entheses and that psoriasis, although possibly absent, will be present in a patient's past personal or family history. There was no consensus among the rheumatologists regarding normalisation of C-reactive protein levels and erythrocyte sedimentation rates defining remission. The specialists believed that clinical remission was achieved more frequently and for longer among patients with PsA than rheumatoid arthritis. The participants believed that neutralising antibodies altered the efficacy of anti-tumour necrosis factor agents and that monoclonal antibodies induced greater production of neutralising antibodies than receptor proteins. However, knowledge was somewhat lacking in relation to the prophylaxis of latent tuberculosis. CONCLUSIONS: The data collected showed that the surveyed rheumatologists had a good knowledge of the diagnosis of early-stage PsA and a good understanding of its management in relation to its clinical phenotype, with the exception of the form having predominantly axial involvement.

Risk of Tuberculosis Reactivation in Patients with Rheumatoid Arthritis, Ankylosing Spondylitis, and Psoriatic Arthritis Receiving Non-Anti-TNF-Targeted Biologics.

Tuberculosis (TB) still represents an important issue for public health in underdeveloped countries, but the use of antitumor necrosis factor agents (anti-TNF) for the treatment of inflammatory rheumatic disorders has reopened the problem also in countries with low TB incidence, due to the increased risk of TB reactivation in subjects with latent tuberculosis infection (LTBI). Over the last 5 years, several non-anti-TNF-targeted biologics have been licensed for the treatment of rheumatoid arthritis, ankylosing spondylitis, and psoriatic arthritis. We reviewed the epidemiology of TB, the role of different cytokines and of the immune system cells involved in the immune response against TB infection, the methods to detect LTBI, and the risk of TB reactivation in patients exposed to non-anti-TNF-targeted biologics. Given the limited role exerted by the cytokines different from TNF, as expected, data from controlled trials, national registries of biologics, and postmarketing surveillance show that the risk of TB reactivation in patients receiving non-anti-TNF-targeted biologics is negligible, hence raising the question whether the screening procedures for LTBI would be necessary.

Long-term costs and outcomes in psoriatic arthritis patients not responding to conventional therapy treated with tumour necrosis factor inhibitors: the extension of the Psoriatic Arthritis Cost Evaluation (PACE) study.

OBJECTIVES: Poor information on long-term outcomes and costs on tumour necrosis factor (TNF) inhibitors in psoriatic arthritis (PsA) are available. Our aim was to evaluate long-term costs and benefits of TNF- inhibitors in PsA patients with inadequate response to conventional treatment with traditional disease-modifying anti-rheumatic drugs (tDMARDs). METHODS: Fifty-five out of 107 enrolled patients included in the study at one year, completed the 5-year follow-up period. These patients were enrolled in 8 of 9 centres included in the study at one year. Patients aged older than 18 years, with different forms of PsA and failure or intolerance to tDMARDs therapy were treated with anti-TNF agents. Information on resource use, health-related quality of life (HRQoL), disease activity, function and laboratory values were collected at baseline and through the 5 years of therapy. Costs (expressed in Euro 2011) and utility (measured by EQ-5D instrument) before TNF inhibitor therapy and after 1 and 5 years were compared. RESULTS: The majority of patients (46 out of 55; 83.6%) had a predominant or exclusive peripheral arthritis and 16.4% had predominant or exclusive axial involvement. There was a statistically significant improvement of the most important clinical variables after 1 year of follow-up. These improvements were maintained also after 5 years. The direct costs increased by approximately €800 per patient-month after 1 year, the indirect costs decreased by €100 and the overall costs increased by more than €700 per patient-month due to the cost of TNF inhibitor therapy. Costs at 5 year were similar to the costs at 1 year. The HRQoL parameters showed the same trends of the clinical variables. EQ-5D VAS, EQ-5D utility and SF-36 PCS score showed a significant improvement after 1 year, maintained at 5 years. SF-36 MCS showed an improvement only at 5 years. CONCLUSIONS: The results of our study suggest that TNF blockers have long-term efficacy. The higher cost of TNF inhibitor therapy was balanced by a significant improvement of HRQoL, stable at 5 years of follow-up. Our results need to be confirmed in larger samples of patients.

Quality of life and unmet needs in patients with inflammatory arthropathies: results from the multicentre, observational RAPSODIA study.

OBJECTIVE: The observational RAPSODIA (RA, PsA and spondylitis including AS) study was planned to assess, in patients with RA, AS and PsA, their involvement in medical decisions, quality of life and unmet needs 15 years after the introduction of biologic therapies in Italy. METHODS: Patients completed a questionnaire during their scheduled rheumatology consultation. They rated their satisfaction with disease knowledge on a 5-point scale (1 = not at all satisfied, 5 = totally satisfied). Self-efficacy, defined as judgement of one's own ability to achieve given levels of performance and exercise control over events, was measured using the pain subscale of the Arthritis Self-Efficacy Scale. Patients' global assessments of pain, fatigue and disease activity were recorded on 100 mm visual analogue scales (0 = best status, 100 = worse status). Disease activity status was assessed using standard tools. Health status was measured using the 36-item Short Form Health Survey and the Italian version of the HAQ. RESULTS: Ninety-eight per cent of patients reported that their health care practitioner used understandable terms to explain their condition. Joint issues and general symptoms (e.g. fatigue and malaise) were common. All measures of disease activity and self-efficacy scores were markedly better in patients receiving biologic vs conventional therapy. Biologic therapy recipients were more productive at work. CONCLUSION: These results confirm that some patients with rheumatic diseases are not satisfied with the level of information they receive about their treatments. Biologic therapy appears to be an important advance, with patients receiving this form of treatment having improved symptoms and productivity. However, patients still report unmet needs. Thus further research, and perhaps new and more effective therapies, along with better education and multidisciplinary collaboration, are required to improve outcomes.

Maintenance of improvement in spinal mobility, physical function and quality of life in patients with ankylosing spondylitis after 5 years in a clinical trial of adalimumab.

OBJECTIVE: Chronic pain and progressive loss of physical function with AS may adversely affect health-related quality of life (HRQoL). The objective of this study was to assess the 5-year data regarding spinal mobility, physical function and HRQoL in patients with AS who participated in the Adalimumab Trial Evaluating Long-term Efficacy and Safety for AS (ATLAS) study. METHODS: Patients received blinded adalimumab 40 mg or placebo every other week for 24 weeks, then open-label adalimumab for up to 5 years. Spinal mobility was evaluated using linear BASMI (BASMIlin). BASDAI, total back pain, CRP, BASFI, Short Form-36 and AS quality of life (ASQoL) were also assessed. Correlations between BASMIlin and clinical, functional and ASQoL outcomes after 12 weeks and after 5years of adalimumab exposure were evaluated using Spearman's rank correlation. Associations were further analysed using multivariate regression. RESULTS: Three hundred and eleven patients received ≥1 dose of adalimumab; 125 of the 208 patients originally randomized to adalimumab received treatment for 5 years. Improvements in BASMIlin were sustained through 5 years, with a mean change of -0.6 from baseline in the population who completed 5 years of treatment with adalimumab. Improvements in disease activity, physical function and ASQoL were also sustained through 5 years. BASMIlin was significantly correlated with all evaluated clinical outcomes (P < 0.001). The highest correlation was with BASFI at 12 weeks (r = 0.52) and at 5 years (r = 0.65). Multivariate regression analysis confirmed this association (P < 0.001). CONCLUSION: Treatment with adalimumab for up to 5 years demonstrated sustained benefits in spinal mobility, disease activity, physical function and HRQoL in patients with active AS. Spinal mobility was significantly associated with short- and long-term physical function in these patients. TRIAL REGISTRATION: Clinicaltrials.gov; https://clinicaltrials.gov/NCT00085644.

Systemic autoimmune disease in asbestosis rapidly responding to anti-interleukin-1beta antibody canakinumab: a case report.

BACKGROUND: Asbestosis is characterized by lung and pleural fibrosis and by immune system dysregulation, with autoantibody production and systemic immune-mediated disease. No specific therapies are available for asbestosis. Recently, the pivotal pathogenic role exerted by interleukin-1beta has been recently reported. CASE PRESENTATION: We treated with anti-interleukin 1 beta targeted antibody canakinumab a 67 year old man with asbestosis and long lasting systemic autoimmune features. A dramatic improvement in clinical manifestations was observed at 1 week after the first injection, with complete clinical remission at 4 months. CONCLUSION: This case suggests new perspectives for the treatment of asbestosis and its systemic features.

Uveitis in Spondyloarthritis: An Overview.

Autoimmune anterior uveitis (AU) accounts for at least half of the cases of noninfectious uveitis, and similarly to spondyloarthritis (SpA), its occurrence is related to HLA-B27 positivity. AU is significantly more frequently found in HLA-B27-positive subjects with SpA and is characterized by unilateral eye involvement, marked tendency to recur with involvement of both eyes in alternate fashion, and has good prognosis in the majority of cases. The estimated frequency of SpA in patients with AU is around 50%, whereas AU in SpA has been reported in at least 30% of cases. Across the SpA disease spectrum, AU has a frequency peak of 33.4% in patients with ankylosing spondylitis, while the estimated prevalence in psoriatic arthritis (PsA) and inflammatory bowel disease-associated SpA is 2%-25%, and 25%, respectively. In early PsA, the frequency of AU has been found in 9% of patients. The wide range of prevalence reported in PsA may be explained by the variable sets of classification criteria used for patient selection and the different length of followup. AU may precede the clinical features of SpA, may be present at diagnosis, or may complicate the SpA clinical course. However, the occurrence of AU in SpA as well as AU flares has been reduced through treatment of SpA with anti-tumor necrosis factor-α agents.

The adherence to ASAS classification criteria and to ASAS recommendations for the use of anti-TNH-alpha agents in axial spondyloarthritis.

OBJECTIVES: To determine the adherence of practicing rheumatologists, before and after an educational project, to Assessment of SpondyloArthritis international Society (ASAS) classification criteria and to ASAS recommendations for the use of anti-tumor necrosis factor (TNF)-alpha agents in patients with axial spondyloarthritis (SpA). METHODS: The project involved 53 rheumatologists attending 2 educational meetings on an update of SpA. Each meeting included interactive sessions on 1) clinical cases, 2) clinimetric evaluation, including ASAS core set for daily practice and 3) imaging. Diagnostic and therapeutic approach of each participant was tested using short clinical cases, obtained from real-life rheumatology settings, at the beginning and at the end of this educational project. Each case for diagnostic (n=10) or therapeutic purpose (n=10) had 10 possible choices. Each participant gave a score from 0 (total disagreement) to 10 (total agreement) for each choice. RESULTS: At baseline, the rheumatologists had an excellent agreement with ASAS classification criteria for axial SpA and anti-TNF-alpha treatment according to ASAS recommendations with a further significant improvement after the educational programme. In axial SpA cases with acute anterior uveitis (AU) or Crohn's disease, anti-TNF-alpha treatment was indicated mainly as monoclonal anti-TNF antibody. In presence of elevated levels of CRP, anti-TNF option has been considered useful. CONCLUSIONS: Practicing rheumatologists had a satisfying adherence to ASAS classification criteria and to ASAS recommendations for the use of anti-TNF-alpha agents for patients with axial SpA. Extra-articular manifestations and other variables might play a role in the decision-process of the management of axial SpA.