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.

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.

Autoantibodies and Rheumatologic Manifestations in Hepatitis C Virus Infection.

HCV is a virus that can cause chronic infection which can result in a systemic disease that may include many rheumatologic manifestations such as arthritis, myalgia, sicca syndrome, cryoglobulinemia vasculitis as well as other non-rheumatological disorders (renal failure, onco-haematological malignancies). In this population, the high frequency of rheumatoid factor (45-70%), antinuclear (10-40%) and anticardiolipin (15-20%) antibodies is a B-cell mediated finding sustained by the infection. However, the possibility that a primitive rheumatic pathology may coexist with the HCV infection is not to be excluded thus complicating a differential diagnosis between primitive and HCV-related disorders.

Cardiovascular Organ Damage in Clinical Subtypes of Systemic Sclerosis: Arterial Stiffness and Echocardiography Might Not Be the Ideal Tools for Patient Risk Stratification.

BACKGROUND: Vascular damage is recognized as a diagnostic landmark in systemic sclerosis (SSc), both in its limited and diffuse subtypes. Early detection at a subclinical stage with transthoracic echocardiography (TTE) and carotid femoral pulse wave velocity (cfPWV) may be helpful in therapeutic planning and management. Aim of the Study. The aim of the study was to evaluate presence of subclinical cardiovascular damage in patients with limited and diffuse SSc in comparison with a cohort of healthy individuals. METHODS: Consecutive patients with limited and diffuse SSc underwent complete TTE and cfPWV and a complete review of clinical data. As controls, 23 healthy subjects with similar hemodynamic profiles were selected. RESULTS: 41 patients (35 female, aged 56.9 years), 21 with diffuse and 20 with limited SSc, were recruited. Past medical history, cardiovascular risk factors, gender distribution, and disease duration were similar in the two groups as well as TTE parameters and hemodynamic indexes-cfPWV (6.5 [6-6.8] vs. 7.0 [6.2-8.5], p=0.24) and augmentation index (145.6 ± 14.2 vs. 149 ± 20.6, p=0.52). Patients with limited SSc were 10 years older than patients with diffuse SSc. In the multiple regression analysis, only age (p=0.0154) and disease duration (p=0.0467) resulted as the significant determinant of cfPWV. When compared to healthy controls, no significant difference emerged in TTE or hemodynamic indexes. CONCLUSION: In SSc, cfPWV increases with age, with no additional impact of pathology or subtype. Vascular damage in the SSc population is not accurately reflected in increased arterial stiffness, as evaluated with cfPWV, or classically defined echocardiographic findings of organ damage (i.e., left ventricular concentric remodelling and increased filling pressures).

Rheumatic manifestations in inflammatory bowel disease.

Rheumatic manifestations are the most frequent extra-intestinal manifestations (EIMs) in inflammatory bowel disease (IBD) patients, and they are responsible for a relevant reduction of quality of life. IBD is associated with a variety of musculoskeletal manifestations such as arthritis and non-inflammatory pain as well as with metabolic diseases, such as osteoporosis. Different imaging techniques (primarily ultrasound, magnetic resonance imaging and X-rays) can help the clinician to correctly identify the nature of manifestations and to treat the patient accordingly. Nowadays, in the setting of IBD-related arthritides, different drugs are available and can be effective on both articular and intestinal involvement. Therefore, a multi-disciplinary approach provides an early diagnosis and a better clinical outcome that can only be given from the recognition and consideration of the different EIMs. As for rheumatic manifestations, namely IBD-related arthritis, an early intervention allows to control disease activity and to prevent structural damage.

Golimumab effectiveness in biologic inadequate responding patients with rheumatoid arthritis, psoriatic arthritis and spondyloarthritis in real-life from the Italian registry GISEA.

OBJECTIVE: To evaluate the clinical effectiveness of golimumab in biologic inadequate responder (IR) patients with Rheumatoid arthritis (RA), Spondyloarthritis (SpA), and Psoriatic arthritis (PsA). METHODS: We analyzed 1424 patients on golimumab from the GISEA registry. Drug survival was estimated by Kaplan-Meier analysis in biologic-naïve, 1-biologic IR, ≥2-biologics IR patients. Hazard ratios (HRs) of discontinuing golimumab at 2 years were assessed by multivariate Cox regression. Patients achieving CDAI based low disease activity (LDA) or BASDAI<4 were calculated at 6 and 12 months. RESULTS: In RA (n.370), the 2-years survival on golimumab was 61.4% in 1-biologic IR, 51.9% in≥2-biologics IR, and 73.1% in biologic-naive patients (P=0.002 vs≥2-biologics IR). In SpA (n.502), the survival was similar among 1-biologic IR (80%), ≥2-biologics IR (76.5%), and biologic-naive (74.6%) patients (P>0.05). In PsA (n.552) the survival was 72% in 1-biologic IR, 72.5% in≥2-biologics IR, and 71.8% in naïve-biologic (P>0.05). Predictors of golimumab discontinuation were monotherapy (HR 1.65) for RA, female gender for SpA (HR 2.48) and PsA (HR 1.57). In RA, patients on CDAI-LDA were lower in 1-biologic IR (40%) or≥2 biologics IR (40%) than in biologic-naïve (60%) group at 6 months (P=0.02), but no difference was observed at 12 months. In PsA and SpA, the percentage of patients on CDAI-LDA or BASDAI<4 at 6 months was almost identical across the subgroups. CONCLUSIONS: Golimumab had similar effectiveness in biologic-failure and biologic-naïve SpA and PsA, but seems to be less effective in multi-failure RA patients, especially as monotherapy. The best outcomes were seen in male patients.

Double Glomerulonephritis in a Patient with Ankylosing Spondylitis Treated with Biologic Agent: Extrarticolar Involvement or Anti-Tumor Necrosis Factor Alpha Injury? A Case-Based Review.

With the widespreading use of biologic drugs, reports of renal injury are increasing, most of which belong to the spectrum of secondary autoimmune syndromes. We present the case of a young man affected by Ankylosing Spondylitis, treated with tumor necrosis factor alpha inhibitors (Anti-TNF) that develop a peculiar renal damage: a coexistence of 2 glomerulonephritis due to different noxae, an IgA nephropaty with a Membranous nephropathy. The first one probably related to the rheumatologic disease, the second one related to Anti-TNF. Despite the underlying mechanisms, the renal involvement both related to Ankylosing Spondylitis and secondary to biologic treatment are currently rare and not predictable. Regular control of renal function and urinalysis during treatment with anti-TNF is mandatory. A concomitant treatment with Disease Modifying Anti Rheumatic Drugs or eventually a low dose of steroids may prevent the formation of anti-drug antibodies and could limit the renal damage related to this phenomenon.

Efficacy and safety of a single switch from etanercept originator to etanercept biosimilar in a cohort of inflammatory arthritis.

AntiTNF-α biosimilars are broadly available for the treatment of inflammatory arthritis. There are a lot of data concerning the maintenance of clinical efficacy after switching from originators to biosimilars; therefore, such a transition is increasingly encouraged both in the US and Europe. However, there are reports about flares and adverse events (AE) as a non-medical switch remains controversial due to ethical and clinical implications (efficacy, safety, tolerability). The aim of our work was to evaluate the disease activity trend after switching from etanercept originator (oETA-Enbrel) to its biosimilar (bETA-SP4/Benepali) in a cohort of patients in Turin, Piedmont, Italy. In this area, the switch to biosimilars is stalwartly encouraged. We switched 87 patients who were in a clinical state of stability from oETA to bETA: 48 patients were affected by Rheumatoid Arthritis (RA),26 by Psoriatic Arthritis (PsA) and 13 by Ankylosing Spondylitis (AS).We evaluated VAS-pain, Global-Health, CRP, number of swollen and tender joints, Disease Activity Score on 28 joints (DAS28) for RA, Disease Activity in Psoriatic Arthritis (DAPSA) for PsA, Health Assessment Questionnaire (HAQ) and Health Assessment Questionnaire for the spondyloarthropathies (HAQ-S),Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) for AS patients. 11/85 patients (12.6%) stopped treatment after switching to biosimilar etanercept. No difference was found between oETA and bETA in terms of efficacy. However, some arthritis flare and AE were reported. Our data regarding maintenance of efficacy and percentage of discontinuation were in line with the existing literature.

Rheumatologic manifestations of hepatitis C in the era of direct-acting antiviral agents.

Beyond the classic hepatic complications, hepatitis C (HCV) infection is considered as a systemic disease, since extrahepatic manifestations become clinically evident in 40% to 70% of the patients and it can frequently include rheumatic ones. Furthermore, HCV can promote the production of several autoantibodies, thus complicating the differential diagnosis between primitive and HCV-related rheumatic disorders. The recent development of direct-acting antivirals (DAA) against HCV has revolutionized the field, reducing the damage stemming from systemic inflammatory phenomena and persistent immune activation associated with continuous HCV replication. Our review focuses on the main rheumatologic manifestations associated with chronic HCV infection as well as the impact of DAA interferon-free treatments on such extrahepatic clinical involvement.

The clinical presentation in adulthood of juvenile idiopathic arthritis.

Juvenile idiopathic arthritis (JIA) is a chronic systemic inflammatory disease, which affects children and adolescents, characterized by significant differences when compared to inflammatory rheumatisms in adulthood. Today, in a panorama enriched in the last decades with great improvements in the diagnostic and therapeutic field, a far from negligible portion and an increasing number of patients with JIA require the continuation of treatments in adulthood. This specific population of patients, given the high incidence of extra-articular manifestations, residual irreversible disabilities, comorbidities related to an inflammatory process and extended immunosuppressive treatments during the age of development, requires precise attentions in the follow-up and a multidisciplinary approach characterized by different clinical, psychological and social aspects.

Ultrasound-guided intra-articular injection: efficacy of hyaluronic acid compared to glucocorticoid in the treatment of knee osteoarthritis.

BACKGROUND: Osteoarthritis (OA) is a degenerative joint disease which causes pain and functional impairment in adults over 50 years old with consequent important disability. Unfortunately, there is no definitive cure for OA, thus the approach is characterized by multiple treatments that can manage its symptoms. Even though data from randomized controlled trials and meta-analyses indicate that intra-articular hyaluronic acid (IAHA) offers the best benefit/risk balance among the various pharmacologic treatments to improve OA-related knee pain, there is a lack of agreement among national and international guidelines about such uses of IAHA for the medical management of symptomatic knee OA. To minimize confounding factors and biases, the aim of our study was to evaluate the efficacy of the different weight and concentration of IAHA treatment in patients suffering from knee OA comparing to glucocorticoids (GC) joint injections. Furthermore, to make the procedure more accurate and assessment more objective, we use ultrasonography (US) with power Doppler (PWD) to help us differentiate between active and inactive inflammation within joints and periarticular soft tissues. METHODS: We performed a retrospective evaluation of a cohort of patients with knee OA, diagnosed according to the ACR criteria, treated by US-guided joint injection of HA and GC. The patients were catalogued according to the type of treatment they underwent: group A, patients treated with HA (1.5%) >1500 kDa (three US-guided knee injections one week apart); group B, patients treated with HA (2%) 800-1200 kDa (three US-guided knee injections one week apart); group C, patients treated with glucocorticoids (three US-guided knee injections of triamcinolone acetate 40 mg one week apart). All patients were monitored for 6 months, evaluating: subjective pain using a 10-cm Visual Analogue Scale; pain, stiffness, and functionality using the Western Ontario and McMaster Universities Arthritis Index (WOMAC); the concomitant intake of anti-inflammatory and/or analgesic drugs through a questionnaire; and US results by grey scale and PWD. RESULTS: A total of 171 patients affected by knee OA were evaluated (women 72.3%) with a mean age of 69.3±4.1 years. All the subjects analyzed showed a pain reduction at 6 months after treatment (group A: -39.5; group B: -36.9; group C: -30.8). The difference between the three groups was statistically significant (Kruskall-Wallis P=0.001) and in particular between group A and group C (P=0.000) and between group B and group C (P=0.005), but not between A and B (P=0.258). WOMAC was statistically significantly improved from baseline in all groups examined (group A: -11.9; group B: -14.9; group C: -11.2). The PWD score showed a statistically significant improvement in group B (-0.64) even after 6 months (P=0.004). All patients in the different groups showed a statistically significant reduction of concomitant therapy compared to baseline with respect to paracetamol and non-steroidal anti-inflammatory drugs (NSAIDs)/COX2 therapy, while only group B showed a statistically significant reduction for opioids. CONCLUSIONS: This study demonstrated the efficacy of OA treatment with medium molecular weight HA in favor of the higher concentration of HA that may affect the reduction of pro-inflammatory mediators. Furthermore, US monitoring allowed to evaluate aspects related to synovial involvement, which cannot be appreciated with standard imaging.

Serological and clinical profile of systemic sclerosis: analysis in a cohort of patients from a single center in Northern Italy.

BACKGROUND: The purpose of this study was to identify the frequency of autoantibodies among patients affected by systemic sclerosis (SSc) in our Rheumatology Center and analyze the correlation between serological and clinical presentations. METHODS: An automated fluoro-enzyme-immunoassay is used for the qualitative detection of sixteen antibodies: anti-dsDNA, antiRo52, antiRo60, antiSS-B, antiTopoisomerasi-I, antiCENP-B, anti-fibrillarin, antiMi-2, anti-Sm, antiU1sn-RNP, antiRNP70, antiPm/Scl100, antiPCNA, antiJo-1, antiRibosomal-P, antiRNA-Polymerase-III. These parameters were further correlated with clinical presentation of the disease. RESULTS: One-hundred and six patients who fulfilled the ACR classification criteria of SSc have been screened. Similarly to the findings of other studies, a strong association between anti-Centromere antibodies and clinical indicators of better prognosis has been showed; conversely, the anti-Scl70 antibodies are associated with diffuse SSc and higher severity. Some antibodies (antiR052, antiU1RNP) are correlated with a diagnosis of autoimmune overlap. A protective effect of AntiCentromere regarding pulmonary fibrosis and skin ulcers has been shown (P<0.05). The presence of AntiScl70 correlated with cardiac involvement (arrhythmias, pericarditis and myocarditis) and the Anti-U1RNP correlated with the presence of skin ulcers. CONCLUSIONS: The diagnostic importance of SSc antibodies against a variety of nuclear and cytoplasmic antigens has become increasingly recognized, as confirmed by the inclusion into 2013American College of Rheumatology (ACR)/the European League Against Rheumatism clinical classification criteria for SSc. A number of studies reported variable geographic rates of antibody prevalence in SSc, which may be related to either genetic or environmental factors. However, the association of specific antibodies with clinical manifestations continues to be claimed. New testing methods which include a wider spectrum of detectable antibodies may support the daily rheumatological and dermatological clinical practice in defining clinical subsets of disease and provide prognostic information.

Abatacept and granulocyte-colony stimulating factor in a patient with rheumatoid arthritis and neutropenia.

Neutropenia in patients with inflammatory diseases increases the risk of infection due to the disease itself and the related immunosuppressive treatments. We report the case of a 54-year-old female with rheumatoid arthritis and following development of chronic neutropenia. All investigations excluded pathogenic relations with drugs and/or other clinical situations; the gravity of neutropenia required a treatment with G-CSF and the increased articular inflammatory activity justified a biologic-therapy, abatacept (CTLA4 inhibitors). The juxtaposition of immunostimulants and immunosuppressors led to great effectiveness for both hematological and rheumatic issues. To date, while some biologic drugs (TNF, IL6R and CD20 inhibitors) have reported relations with neutropenia, no such relevance subsists for Abatacept. Our case reports the experience of the safe effective use of abatacept and G-CSF for 8 years.