Subcutaneous infliximab CT-P13 without intravenous induction in psoriatic arthritis: A case report and pharmacokinetic considerations.

INTRODUCTION: The biosimilar CT-P13, the first and only subcutaneous (SC) infliximab formulation, is recommended for patients with psoriatic arthritis (PsA) and can be administered as a maintenance treatment, to be started 4 weeks after the induction treatment with 2 intravenous (IV) infliximab infusions. OBJECTIVE: To evaluate treatment with SC infliximab without prior IV infusion induction to meet patient needs. MATERIALS AND METHODS: After approval by the ethics review board and based on the schedule approved for rheumatoid arthritis, SC induction was performed with infliximab CT-P13 120 mg weekly for 4 weeks, followed by an injection of 120 mg every 2 weeks. RESULTS: After 4 months of therapy, joint symptoms were resolved, inflammation parameters were normalized (erythrocyte sedimentation rate) reduced from 42 to 16 mm/h, and C-reactive protein from 1.74 to 0.43 mg/dL), and clinical assessment parameters were improved. After 9 months of therapy, the clinical data remained stable, with no adverse events or local side effects. CONCLUSION: SC infliximab was successfully used without previous IV infusion induction. Although, to date, the induction of PsA treatment via the SC route is not foreseen, the known pharmacokinetic properties and the outcome improvements observed in our patient show that subcutaneous treatment induction, as is already done in the treatment of rheumatoid arthritis, is also possible.

Persistence, effectiveness and safety of ustekinumab compared to TNF inhibitors in psoriatic arthritis within the Italian PsABio cohort.

OBJECTIVES: To compare real-world persistence, effectiveness and tolerability of ustekinumab versus TNF inhibitors (TNFi) in psoriatic arthritis (PsA). METHODS: One-year data from Italian subjects enrolled in the PsABio study (PsA patients receiving 1st- to 3rd-line treatment with ustekinumab or TNFi) were evaluated. Treatment persistence was analysed using Kaplan-Meier curves; hazard ratios (HR) of stopping treatment, and the corresponding 95% confidence intervals (CI), were computed through Cox regression models. Proportions of patients reaching clinical effectiveness endpoints were analysed using logistic regression, including propensity score (PS) adjustment for imbalanced baseline covariates, and non-response imputation if treatment was stopped/switched. RESULTS: Among 222 participants with follow-up data (effectiveness set), 101 received ustekinumab and 121 TNFi. In the ustekinumab group, 74.3% continued treatment up to 12±3 months compared to 63.6% in the TNFi group. Ustekinumab showed better persistence than TNFi, overall and in specific subgroups (females, monotherapy without methotrexate, BMI <25 or >30 kg/m2, patients receiving ustekinumab as 2nd-line treatment instead of a second TNFi). Overall, the PS-adjusted HR of treatment discontinuation was 0.46 (95% CI: 0.26-0.82) for ustekinumab vs. TNFi. cDAPSA LDA/remission was achieved in 43.5% of ustekinumab and 43.6% of TNFi-treated patients, while MDA was achieved in 24.2% and 28.0% of patients, respectively. After PS adjustment, odds ratios of clinical effectiveness did not differ significantly. Both treatments showed an acceptable safety profile. CONCLUSIONS: This prospective, real-life study found a better persistence of ustekinumab than TNFi in PsA patients. At 1 year, both treatments showed similar effectiveness.

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.

A real-world economic analysis of biologic therapies for psoriatic arthritis in Italy: results of the CHRONOS observational longitudinal study.

BACKGROUND: Psoriatic arthritis (PsA) is a chronic, immune-mediated, spondyloarthropathy characterised by musculoskeletal signs and symptoms with associated joint pain and tenderness. The average worldwide PsA prevalence is 133/100,000, while in the Italian population is 90-420/100,000. Traditionally, nonsteroidal anti-inflammatory drugs, glucocorticoid, and disease-modifying antirheumatic drugs have been used in the treatment of PsA. However, for those patients who are not adequately controlled with conventional therapies, the new biologics compounds represent a valid option. Biologic therapies have been shown to be more effective but also more expensive than conventional systemic treatments. Based on the CHRONOS study, the economic analyses presented in this paper aim to assess the annualised direct costs and the cost-per-responder of biologics in a real-world context assuming the Italian National Health System perspective. METHODS: The economic assessments were carried out on the overall cohort of patients, and on the tumour necrosis factor alpha inhibitors (TNFi) and the secukinumab subgroup, the most prescribed biologic therapies within the CHRONOS study. RESULTS: The annual economic impact of PsA in the overall group was €12,622, €11,725 in the secukinumab subgroup, and €12,791 in the TNFi subgroup. Biologics absorbed the main expenditure costs in the treatment of PsA accounting for about the 93% of total costs. At 6 months, secukinumab performed better in all the considered outcomes: cost-per-responder according to EULAR DAS28 and ACR50 response criteria were €12,661- €28,975, respectively, while they were €13,356 - €33,368 in the overall cohort and €13,138 - €35,166 in the TNFi subgroup. At 12 months secukinumab remained the subgroup with the lowest cost-per-responder ratio in EULAR DAS28 and ACR50 response criteria, while TNFi subgroup was the lowest one considered the ACR20. CONCLUSION: Despite some potential methodological limitations, our cost-per-response analysis provides physicians and payers additional insights which can complement the traditional risk-benefit profile assessment and drive treatment decisions.

Impact of one-year treatment with biotechnological drugs on work ability in patients with rheumatoid arthritis in Italy: a prospective real-life study.

OBJECTIVES: We aimed to evaluate the impact of biologic therapy on work productivity outcomes in an Italian real-life cohort of biologic-naïve patients with active rheumatoid arthritis (RA). METHODS: This observational prospective multicentre study enrolled RA patients in working age with an active disease who started their first biologic agent. Every patient completed the RA-specific Work Productivity Survey (WPS-RA) at each clinical evaluation (baseline, 6 and 12 months). The primary outcome of the study was the productivity gain at 12 months from the beginning of the biologic treatment, compared to baseline, assessed in terms of absenteeism and presenteeism reduction, both for employed and unemployed subjects. Linear regression analyses were performed to assess the impact of patient- and disease-related variables on productivity gain. RESULTS: Overall, 100 patients were enrolled and 85 completed the study. All indexes of disease activity and functional ability were significantly improved from baseline already at 6 months. At 12 months, the 55 employed subjects showed a significant reduction in the mean number of days of work missed (absenteeism) and of reduced productivity (presenteeism). A significant reduction in the mean number of days of household work missed was observed for all patients. At multivariate analysis, functional disability had a significant negative impact on all parameters of household work productivity, while the achievement of a low disease activity or remission was inversely correlated with presenteeism. CONCLUSIONS: One year of treatment with a biological drug significantly impacts on the disease activity and work ability of RA patients and allows economic gains due to productivity improvement.

Prevalence of hepatitis B virus infection and risk of reactivation in rheumatic population undergoing biological therapy.

OBJECTIVES: Hepatitis B (HBV) is a common comorbidity among rheumatic patients. The prevalence of HBV infection and the rate of reactivation remain unclear. The literature data suggested a higher risk in chronic than in past infection. Currently, the literature data are mostly focused on anti-TNF and rituximab. This retrospective observational study aimed to analyse the prevalence of HBV infection and the risk of viral reactivation in a population of rheumatic patients undergoing anti-TNF and non-anti-TNF agents. METHODS: We analysed 1216 rheumatic patients, treated with both csDMARDs and bDMARDs between 2006 and 2017. Serologic markers for HBV (HBsAg, anti-HBs, anti-HBc) were performed prior and during biologic treatment. Patients with chronic or resolved infection were monitored every 3 months. RESULTS: The prevalence of HBV in our cohort was 15.7% (chronic infection: 0.4%, resolved infection: 12.6%, anti-HBc positivity alone: 2.6%). 12 (6.2%) out of 191 HBV infected patients experienced a reactivation. All of them showed markers of past infection. One patient experienced HBV reactivation despite lamivudine. Only one patient experienced acute hepatitis, probably due to the interruption of immunosuppressors in anticipation of surgery, not preceded by any HBV prophylactic treatment. CONCLUSIONS: HBV reactivation is a rare event in patients treated with a bDMARD and it can also occur while taking lamivudine, not only in chronic carriers (as per the literature data) but also in inactive ones. Regular screening followed by prompt treatment can prevent symptoms or complications. Due to the risk of hepatitis following the immune reconstitution, an antiviral therapy should be considered in the case of sudden discontinuation of csDMARDs or bDMARD.

Efficacy and retention rate of adalimumab in rheumatoid arthritis and psoriatic arthritis patients after first-line etanercept failure: the FEARLESS cohort.

Few studies have compared the efficacy of switching from etanercept to adalimumab in the real-life setting in rheumatoid arthritis (RA) and psoriatic arthritis (PsA). This study evaluated the 2-year retention rate and 12-month efficacy of adalimumab in RA and PsA patients, previously treated with etanercept. RA and PsA patients from 11 Italian Rheumatology Units received adalimumab after first-line etanercept failure. Two-year adalimumab retention rate was calculated by the Kaplan-Meier method and Cox proportional hazard models were developed to examine predictors of drug persistence. Univariate and multivariate logistic regression analyses were developed to examine potential predictors of 12-month DAS-28 remission. The study population included 117 RA (disease duration of 10.1 ± 7.7 years and baseline DAS28-ESR of 4.97 ± 1.3) and 102 PsA (disease duration of 7.1 ± 5.1 years and baseline DAPSA of 24.6 ± 11.8). The 2-year retention rate was 48.2% in RA and 56.5% in PsA patients. Concomitant methotrexate treatment was not associated with increased drug survival in both groups. Similarly, cause of etanercept discontinuation or treatment duration was not associated with retention rate. 12-month remission and low disease activity were achieved, respectively, in 27.3% and 23.9% of RA patients and 27.4% and 23.5% PsA of patients. In multivariate models, etanercept discontinuation due to inefficacy (OR 0.27, 95% CI 1.03-0.73; p = 0.009) and baseline DAS-28 (OR 0.45, 95% CI 0.29-0.69; p < 0.001) remained significant negative predictors of remission in RA patients. No variable was associated with remission in PsA patients. Adalimumab after etanercept failure was highly effective and safe in both RA and PsA patients.

Pain appraisal and quality of life in 108 outpatients with rheumatoid arthritis.

Individual differences in emotional functioning, pain appraisal processing, and perceived social support may play a relevant role in the subjective experience of pain. Due to the paucity of data regarding individuals with Rheumatoid Arthritis (RA), the present study aimed to examine pain intensity, emotional functioning (psychological distress and alexithymia), pain appraisal (pain beliefs, pain catastrophizing, and pain-related coping strategies) and social support, and their relationships with the health-related quality of life (HRQoL) in patients with RA. Data were collected from 108 female patients diagnosed with RA. Clinically relevant levels of depressive and anxiety symptoms assessed by the HADS subscales were present in 34% and 41% of the patients, respectively, and about 24% of them exhibited the presence of alexithymia. The results of hierarchical multiple regression analyses showed that pain intensity, alexithymia, the maladaptive beliefs regarding the stability of pain and the coping strategy of guarding explained 54% of the variance in the physical component of HRQoL (p < 0.001). Depression subscale of the HADS, alexithymia, the coping strategy of resting, and the rumination factor of pain catastrophizing significantly explained 40% of the variance in the mental component of HRQoL (p < 0.001). The present findings provide evidence regarding the importance of emotional functioning and pain appraisal in the negative impact of RA on patients' quality of life. These findings provide additional evidence for the biopsychosocial model of chronic pain, further supporting the complex interaction between emotional, cognitive, and behavioral processes in patients with chronic pain.

Risk factors of suspected spondyloarthritis among inflammatory bowel disease patients.

Background: Occurring in approximately 20-30% of patients, spondyloarthritis is the most common extraintestinal manifestation in inflammatory bowel disease (IBD).Aims: To look for risk factors of spondyloarthritis among inflammatory bowel disease patients.Methods: We modified the STRIPP questionnaire created for psoriatic patients and we created a rapid questionnaire for rheumatologic investigation in IBD patients (STRII). We submitted the questionnaire to all consecutive patients with a known spondyloarthritis in our centre and to patients with a negative rheumatological diagnosis to find the cut-off value. Finally, we prospectively submitted the STRII questionnaire to all consecutive IBD patients in our centre.Results: A cut-off ≥3 correlated with spondyloarthritis with an AUC = 0.91. The STRII questionnaire was submitted to 1147 IBD patients. Two hundred and forty-four out of 1147 (21.3%) collected a STRII score of ≥3. Female sex (p < .0001) and Crohn's disease (p = .023) were risk factors. Patients with a history of at least 1 immunosuppressant or biologic drug (p = .002 and p < .0001, respectively) had a higher rate of positivity to STRII questionnaire.Conclusion: Among IBD patients, females, Crohn's disease, those with a history of at least 1 immunosuppressive or biological therapy are at increased risk of spondyloarthritis.

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.

Coping strategies and perceived social support in fibromyalgia syndrome: Relationship with alexithymia.

Fibromyalgia (FM) is a chronic pain syndrome characterized by high levels of psychological distress and alexithymia, a personality disposition affecting emotional self-awareness. The main aim of the present study was to investigate for the first time the relationship between alexithymia and coping strategies on the one hand, and alexithymia and perceived social support on the other, in a sample of FM patients. To reach this aim, 153 FM patients completed a battery of tests assessing coping strategies, perceived social support, alexithymia, psychological distress and pain intensity. Four regression analyses were performed to assess whether alexithymia was still a significant predictor of coping strategies and perceived social support, after controlling for psychological distress. High levels of both psychological distress and alexithymia were found in our sample of FM patients. Regarding coping strategies, FM patients reported higher scores on problem-focused coping, with respect to the other two coping strategies. The regression analyses showed that the externally-oriented thinking factor of alexithymia significantly explained both problem- and emotion-focused coping, while the difficulty-describing feelings factor of alexithymia proved to be a significant predictor of perceived social support. Only the variance of dysfunctional coping ceased to be uniquely explained by alexithymia (difficulty identifying feelings factor), after controlling for psychological distress, particularly anxiety. These results highlight a negative relationship between alexithymia and both the use of effective coping strategies and the levels of perceived social support in FM patients. An adequate assessment of both alexithymia and psychological distress should therefore be included in clinical practice with these patients.

Quantitative chest computed tomography is associated with two prediction models of mortality in interstitial lung disease related to systemic sclerosis.

Objective: In this multicentre study, we aimed to evaluate the capacity of a computer-assisted automated QCT method to identify patients with SSc-associated interstitial lung disease (SSc-ILD) with high mortality risk according to validated composite clinical indexes (ILD-Gender, Age, Physiology index and du Bois index). Methods: Chest CT, anamnestic data and pulmonary function tests of 146 patients with SSc were retrospectively collected, and the ILD-Gender, Age, Physiology score and DuBois index were calculated. Each chest CT underwent an operator-independent quantitative assessment performed with a free medical image viewer (Horos). The correlation between clinical prediction models and QCT parameters was tested. A value of P < 0.05 was considered statistically significant. Results: Most QCT parameters had a statistically different distribution in patients with diverging mortality risk according to both clinical prediction models (P < 0.01). The cut-offs of QCT parameters were calculated by receiver operating characteristic curve analysis, and most of them could discriminate patients with different mortality risk according to clinical prediction models. Conclusion: QCT assessment of SSc-ILD can discriminate between well-defined different mortality risk categories, supporting its prognostic value. These findings, together with the operator independence, strengthen the validity and clinical usefulness of QCT for assessment of SSc-ILD.

Two-year retention rate of golimumab in rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis: data from the LORHEN registry.

OBJECTIVES: We aimed to provide data on golimumab real-life use in rheumatoid arthritis (RA), psoriatic arthritis (PsA) and ankylosing spondylitis (AS) from a multicentre observational registry of Northern Italy. METHODS: We extracted data of patients who started treatment with golimumab from October 2010, and who had at least one follow-up visit. Data were analysed until a maximum follow-up of 24 months. The two-year retention rate in the three diseases was assessed with Kaplan-Meier estimators. To compare crude survival between diagnoses and lines of treatment we used the log-rank test, while Cox proportional hazard models were used to adjust for confounders. RESULTS: Overall, 410 subjects were included: 180 patients with RA, 110 with PsA and 120 with AS. The two-year retention rate of patients with RA was 47.3%, 48% for PsA, and 62.8% for AS. Crude survival on treatment of patients with AS was significantly higher than that of RA patients (p=0.032), while no significant difference was found between AS and PsA and between RA and PsA. In patients with RA, subjects treated with concomitant sDMARDs showed a lower discontinuation rate than those receiving golimumab alone. The comparison between first and second line of treatment groups did not show any significant difference in mean survival time in patients with RA, PsA and AS. CONCLUSIONS: This is the first report of real-life data on two-year survival on treatment with golimumab in RA, PsA and AS. Golimumab showed a similar retention rate when given as first or second line of treatment.

Psychosomatic syndromes in fibromyalgia.

OBJECTIVES: The aim of this study was to compare the prevalence of psychosomatic symptoms in patients with fibromyalgia (FM) or rheumatoid arthritis (RA). METHODS: Seventy-six consecutive women with FM and 80 with RA without concomitant FM were assessed using the Diagnostic Criteria for Psychosomatic Research (DCPR) interview to evaluate the presence of psychosomatic syndromes. Beck Depression Inventory - II (BDI-II) and Form Y of the State-Trait Anxiety Inventory (STAI-Y) were administered in order to assess the symptoms of anxiety and depression. RESULTS: Significantly higher levels of anxiety and depression were found in the FM patients (p<0.001), and each FM patient (as against 79% of the RA patients) presented at least one DCPR syndrome. Comparisons of psychological distress between the FM patients with and without each of the psychosomatic syndromes revealed high levels of anxiety and depression in the patients with the psychosomatic condition. CONCLUSIONS: The findings of this study highlight the greater presence of psychological distress and psychosomatic syndromes in patients with FM than in RA patients. The FM patients with psychosomatic symptoms also showed high levels of psychological distress. A better understanding of the psychosomatic manifestations of FM syndrome could allow clinicians to structure tailored interventions that take more account of the emotional distress associated with the physical complaints.

A randomised controlled trial comparing duloxetine and acetyl L-carnitine in fibromyalgic patients: preliminary data.

OBJECTIVES: Fibromyalgia syndrome (FMS) is a chronic disorder characterised by widespread musculoskeletal pain, troubled sleep, disturbed mood, and fatigue. Recently published reviews have demonstrated that it is influenced by various psychological aspects, and antidepressants are now considered the treatment of choice for most patients. The aim of this randomised controlled trial was to compare the effects of duloxetine and acetyl L-carnitine on pain, depression, anxiety and well-being in FMS patients. METHODS: Sixty-five female outpatients with FMS diagnosed by a rheumatologist were recruited between January 2011 and May 2012, and randomised to receive duloxetine 60 mg/day or acetyl L-carnitine 1500 mg/day (500 mg t.i.d.). Drug efficacy and side effects were assessed by the same psychiatrist at baseline, and four and 12 weeks later. RESULTS: Both drugs led to a general clinical improvement, with positive effects on pain and depressive symptoms; but neither induced a significant improvement in anxiety. Both drugs had a positive effect on the physical component of the quality of life, but only duloxetine improved the psychological component. CONCLUSIONS: Although they need to be confirmed by further studies, these preliminary findings confirm the efficacy of duloxetine, and suggest that acetyl L-carnitine is also efficacious in improving depressive symptoms, pain, and the quality of life of FMS patients.

Operator-independent quantitative chest computed tomography versus standard assessment of interstitial lung disease related to systemic sclerosis: A multi-centric study.

PURPOSE: Interstitial lung disease (ILD) related to systemic sclerosis (SSc) is assessed with pulmonary functional tests (PFTs) and semi-quantitative scores based on extent of ILD detectable on chest computed tomography (CT). CT quantitative indexes (QCTIs) are promising tools to assess extent of ILD. This study's aim is to evaluate the validity of QCTI compared with that of chest CT standard evaluation and PFTs. Moreover, QCTI differences between patients' subgroups according to prognostic stratifications were investigated. METHODS: ILD-SSc of patients from six rheumatological clinics was routinely assessed with chest CT and PFTs. Patients were clustered according to prognosis based on functional and/or radiological examinations. Finally, chest CTs were processed with OsiriX in order to obtain QCTI. RESULTS: Two hundred fifty-seven SSc patients were enrolled. QCTI correlation between extent of ILD and PFTs range from - 0.60 to 0.58 and from - 0.54 to 0.52, respectively. The majority of QCTI have a different distribution in patients' subgroups based on prognosis. Most of QCTI discriminate patients with an ILD severity leading to a poor prognosis. CONCLUSIONS: QCTI assessment of ILD-SSc is comparable to the evaluation based on chest CT and/or PFTs. QCTI values corresponding to severe ILD were identified. QCTIs are excellent candidates for a new and more reliable SSc-ILD assessment.

Efficacy and Safety of Upadacitinib in Rheumatoid Arthritis: Real-Life Experience from a Prospective Longitudinal Multicentric Study.

BACKGROUND: We provide the first prospective longitudinal multicenter experience on Upadacitinib efficacy and safety profile in Rheumatoid Arthritis (RA) in a real-life context, focusing on clinimetric and ultrasonographic (US) data. METHODS: RA patients referred to three Italian tertiary Centers who started Upadacitinib were enrolled as per ACR/EULAR classification criteria and prospectively reviewed. The primary aim of this study was to assess changes in clinimetric and ultrasonographic scores through time (at baseline, after 1 month, 3 months, and 6 months from the beginning of the therapy). Secondary aims were to: (i) estimate the impact of biologic lines of treatment and concomitant therapies on response to therapy; (ii) explore changes in laboratory parameters; and (iii) find potential predictive factors associated with response to therapy. RESULTS: Seventy-one patients (49 Females and 22 Males) were included. Clinimetric scores, including the Disease Activity Score (DAS28-CRP) and Simplified Clinical Disease Activity Index (SDAI), and US findings (synovial hypertrophy and power Doppler) significantly improved (p = 0.029, p = 0.001, p = 0.001, p = 0.001, respectively). Regression analysis revealed a significant association between the concomitant csDMARDs therapy at baseline and the lack of improvement in synovial hypertrophy [OR -4.824, p = 0.010] as well as with DAS28-CRP [OR -0.690, p = 0.045], whereas the presence of increased ESR or CRP at baseline was able to predict a significant improvement in SDAI [OR 8.481, p = 0.003]. No adverse events, such as deep venous thrombosis, pulmonary embolism, or herpes zoster virus infection, were reported during this study observation. CONCLUSION: Our real-life experience confirms the efficacy of Upadacitinib in terms of clinical and ultrasonographic improvement, as well as displaying a good safety profile.

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.