Objectives: There is evidence that fat tissue may influence the response to therapy in patients with arthritis. The aim of this study was to assess whether the body mass index (BMI) affects rates of clinical remission in patients with psoriatic arthritis (PsA) treated with anti-tumour necrosis factor (TNF)-α biological drugs. Method: We retrospectively studied 135 patients with active peripheral PsA (45 obese, 47 overweight, and 43 normal-weight). Baseline BMI was correlated with the clinical response to adalimumab, etanercept, or infliximab. After 36 months (median, range 6-79) of treatment, disease remission rates were assessed using the Disease Activity Score in 28 joints (DAS28) or the Simplified Disease Activity Index (SDAI). Possible predictors of clinical outcomes were assessed by multivariate analysis. Results: At baseline, BMI was significantly correlated only with the Health Assessment Questionnaire (HAQ) score (r = 0.21, p = 0.02) and not with disease activity. BMI did not predict disease remission or changes in HAQ score following anti-TNF-α therapy. Obese patients showed a significantly higher HAQ score and took significantly lower doses of prednisone than normal-weight or overweight patients, but their disease remission rates on the DAS28 (37%) or the SDAI (21%) were not significantly different from those of the other two groups (44% and 21%, respectively), regardless of the TNF-α inhibitor prescribed. Conclusions: In our retrospective analysis, disease activity and clinical response to anti-TNF-α therapy in PsA do not seem to be affected by BMI. Further prospective studies are needed to confirm these preliminary results. © 2013 Informa Healthcare on license from Scandinavian Rheumatology Research Foundation.

OBJECTIVES: The purpose of the present study was to describe our experience with the recombinant Fab' antibody fragment against TNF-α Certolizumab Pegol (CZP) in patients with Behçet's disease (BD) refractory to standardized therapies and previous biologic agents. METHODS: Retrieved data including demographic characteristics, clinical manifestations, and previous treatments were collected in three different specialized Rheumatologic Units in Italy. In order to evaluate disease activity, the BD current activity form (BDCAF) has been used before starting CZP therapy and at each visit during treatment. RESULTS: Thirteen BD patients (mean age 42.6 ± 8.8 years) with a disease duration of 8.80 ± 6.9 years, underwent CZP treatment for 6.92 ± 3.52 months. Six patients (46.15%) experienced a worsening of symptoms after 4.16 ± 1.21 months, whereas a satisfactory response was achieved in seven patients (53.84%) who were still on CZP therapy at the last follow-up visit (after 9.28 ± 3.03 months of treatment). The mean decrease of BDCAF between the first and last visit was 0.308 ± 1.84 without reaching significant difference (mean 8.3 ± 1.3 and 8 ± 2.08, respectively; p= .51). During the whole study period, CZP was well tolerated in all patients except one who developed a generalized cutaneous reaction after the third administration. CONCLUSIONS: These results suggest that despite an improvement of clinical manifestations has been observed in more than half of the patients, it is not possible to draw firm conclusions about the effectiveness of CZP in BD and further studies with larger cohorts of patients are warranted. Whether the increase of CZP dosage may ensure a better clinical response remains an unsolved issue that needs to be considered.

Background: Shock wave treatment is used for several orthopedic diseases and there are different devices available. Until now, there have been no experimental studies on the effects of these different generators. Methods: We carried out an experimental study to compare the effects of three focused generators (electro-magnetic, piezoelectric and electro-hydraulic) as well as a radial generator on healthy and osteoarthritis chondrocytes. Results: By the analysis of our results, we may exclude significant differences between the different generators, even though there is a greater action specificity for electro-magnetic and piezoelectric generators. Conclusions: The smaller size of the focus of the latter two generators guarantees a greater concentration of energy in the target. The biological effect of the increase of IL-10 and reduction of both N-Cadherin and B-Catenin in chondrocytes in healthy subjects and those affected by osteoarthritis confirms the therapeutic potential of ESWT in cartilage diseases, such as osteoarthritis. In clinical practice it is important to introduce the parameter of total energy. This allows us to standardize the treatment and to manage the variability related to the different types of device and size of the focus. Level of evidence: IIb. © 2017, CIC Edizioni Internazionali s.r.l. All rights reserved.

Adalimumab (ADA) has been shown to be an effective treatment for Behçet's disease (BD)-related uveitis. We aimed at evaluating the cumulative retention rate of ADA during a 48-month follow-up period in patients with BD-related uveitis, the impact of a concomitant use of disease modifying anti-rheumatic drugs (DMARDs) on ADA retention rate, and differences according to the various lines of biologic therapy (ie, first- vs second-line or more). Predictive factors of response to ADA were also investigated.

Dermatomyositis (DM) and polymyositis (PM) commonly cause weakness of the thigh muscles. However, it is debated whether DM and PM affect similar thigh muscles. Muscle oedema on fat-suppressed MRI sequences is thought to represent active inflammation. In this study, we aimed to assess which thigh muscle groups are preferentially inflamed in DM and PM, respectively, using short-tau inversion-recovery MRI sequences.

This study aims to evaluate the drug survival and effectiveness of ustekinumab in psoriatic arthritis (PsA) patients naïve to biologics or inadequate responders to tumor necrosis factor (TNF-IR) inhibitors in real life. PsA patients starting ustekinumab were enrolled from 2014 to 2016. Joint involvement, peripheral or axial, Psoriatic Area Severity Index, Disease Activity Psoriatic Arthritis (DAPSA), Lee Enthesitis Index, Health Assessment Questionnaire, body mass index, comorbidities, co-therapies, mechanism of action, and causes of discontinuation of prior TNFi were collected at baseline, and 6 and 12 months. Twelve-month drug survival was evaluated by Kaplan-Meier curves. Hazard ratios (HRs) of drug discontinuation adjusted for baseline factors were estimated by multiple Cox regression analysis. Percentages of DAPSA-based remission, as crude value and adjusted for drug retention (LUNDEX index), were compared by χ2 test. Mean differences of DAPSA from baseline to 6 and 12 months were compared between naïve and TNF-IR patients by ANOVA. Of 160 PsA patients starting ustekinumab, 54 were naïve and 106 were TNF-IR. Twelve-month drug survival was significantly higher in naïve (87%) than in TNF-IR (68%, p = 0.01). Baseline co-therapy with methotrexate did not increase the persistence on ustekinumab. Naïve patients had the lowest risk of ustekinumab discontinuation (HR 0.27, p = 0.01), and the highest DAPSA-based remission (34%, LUNDEX 26%). Mean differences from baseline of DAPSA was significantly greater in naïve than in TNF-IR patients at 12 months (- 14.4 ± 10 vs. - 4.1 ± 17, p = 0.01). Our data showed that ustekinumab has a good effectiveness in real life and the best outcomes are achieved in biologic-naïve PsA patients.

The primary aim of the study was to evaluate the efficacy of tumor necrosis factor (TNF)-α blockers adalimumab (ADA) and infliximab (IFX) in refractory sight-threatening retinal vasculitis (RV) during a 12-month follow-up period. Secondary aims were to evaluate (i) any impact of concomitant conventional disease-modifying anti-rheumatic drugs (cDMARDs) and different lines of biologic therapy; (ii) any difference in terms of efficacy between ADA and IFX; (iii) consequences of biotherapies on the best-corrected visual acuity (BCVA); (iv) corticosteroid-sparing effect; and (vi) ocular complications during anti-TNF-α treatment. Demographic, clinical, and therapeutic data were retrospectively collected from the medical records and statistically analyzed. Forty-eight patients (82 eyes) were recruited, 22 (45.8%) of which received IFX and 26 (54.2%) ADA. The percentages of patients achieving RV remission within 3 and 12 months were 54 and 86%, respectively. A significant decrease in RV detection was identified from baseline to 3-month (p < 0.0001) and 12-month (p < 0.0001) assessments and between 3-month and 12-month visits (p = 0.004). No differences were identified in terms of RV resolution between (i) patients undergoing monotherapy and those co-administered with cDMARDs at 3-month (p = 0.560) and 12-month (p = 0.611) follow-up; (ii) biologic-naïve patients and those already exposed to other biologics at 3-month (p = 0.497) and 12-month (p > 0.99) visits; and (iii) patients treated with ADA and those treated with IFX (p = 0.357). During the study period, a statistically significant corticosteroid-sparing effect was observed (p = 0.0002), while BCVA values did not significantly change (p = 0.950). Anti-TNF-α monoclonal antibodies have proved excellent results in patients with recalcitrant sight-threatening RV.

Iloprost plays an important role in the treatment of Raynaud's phenomenon (RP), but has transient vasodilatory effects owing to its very short half-time. We aimed to evaluate short- and medium-term haemodynamic effects of iloprost by measuring dorsal finger microvessel blood flow using laser Doppler flowmetry (LDF), in patients with RP associated with systemic sclerosis (SSc).

This study aimed to evaluate the role of interleukin (IL)-1 inhibitors anakinra (ANA) and canakinumab (CAN) in the treatment of Behçet's disease (BD)-related uveitis. Multicenter retrospective observational study includes 19 consecutive BD patients (31 affected eyes) received treatment with anti-IL-1 agents. Data were analyzed at baseline and at 3 and 12 months. The primary endpoint is the reduction of ocular inflammatory flares (OIF). The secondary endpoints are improvement of best corrected visual acuity (BCVA); reduction of macular thickness defined by optical coherence tomography (OCT) and of vasculitis identified with fluorescein angiography (FA); evaluation of statistically significant differences between patients treated with IL-1 inhibitors as monotherapy, subjects also administered with disease modifying anti-rheumatic drugs (DMARDs) and/or corticosteroids as well as between patients administered with IL-1 inhibitors as first line biologic treatment and those previously treated with TNF-α inhibitors. At 12 months, OIF significantly decreased from 200 episodes/100 patients/year to 48.87 episodes/100 patients/year (p < 0.0001). The frequency of retinal vasculitis identified by FA significantly decreased between baseline and 3- and 12-month follow-up visits (p < 0.0001 and p = 0.001, respectively). OIF rate was significantly higher in patients co-administered with DMARDs (81.8 episodes/100 patients/year) than in patients undergoing IL-1 inhibitors as monotherapy (0.0 episodes/100 patients/year) (p = 0.03). No differences were identified on the basis of corticosteroid use and between patients administered with IL-1 inhibitors as first line biologic approach or second line. Steroid dosage was significantly decreased at 12-month visit compared to baseline (p = 0.02). Treatment with IL-1 inhibitors is effective in the management of BD-related uveitis and provides a long-term control of ocular inflammation in refractory and long-lasting cases.

Abnormalities of central pain processing play an important role in the pathophysiology of fibromyalgia (FM). The aims of the present study were to: 1) evaluate habituation of laser-evoked potentials (LEP) to repeated painful stimulation of 1 tender and 2 nontender points; and 2) determine correlations between LEP abnormalities and major clinical features of FM. Fourteen consecutive FM outpatients and 13 normal controls were included. LEP were recorded from scalp designations Fz, Cz, Pz, T3, and T4. The dorsum of the right hand, the right supra-orbital zone, and the right knee (a tender point in all patients) were subjected to repeated CO2 laser stimuli. For each stimulation site, recordings were obtained for 3 consecutive series of 20 stimuli. The 3 main findings in FM patients were: 1) an increased amplitude of vertex LEP and subjective laser pain; 2) decreased habituation of vertex LEP and subjective laser pain; and 3) a correlation between reduced N2 wave habituation and the severity of self-reported depressive symptoms. As with other chronic pain syndromes, the pathophysiology of FM may involve a generalized increase in the perception of painful stimuli and reduced habituation of the sensory cortex. Perspective: Reduced habituation of cortical responses to laser stimuli in FM patients suggests alterations in the pattern of cortical excitability. This is facilitated by depressive symptoms and abnormalities in central neurotransmission. These findings provide further support for the use of medications with effects on the central nervous system in the management of FM.

Objective: To evaluate the risk of serious infections (SIs) in RA patients receiving anti-TNF therapy on the basis of the data included in the GISEA register. Methods: The study involved 2769 adult patients with long-standing RA (mean age 53.2 +/- 13.4 years; mean disease duration 9.0 +/- 8.3 years) enrolled in the GISEA register, who had been treated for at least 6 months with TNF inhibitors or had discontinued therapy due to SI: 837 (30%) treated with infliximab (IFN), 802 (29%) with adalimumab (ADA), and 1130 (41%) with etanercept (ETN). Results: 176 patients had experienced at least one of the 226 Sis during the 9 years of treatment with an anti-TNF agent, an overall incidence of 31.8/1000 patient-years (95% CI 25.2-38.3): 23.7/1000 patient-years (95% CI 13.1-34.2) on ADA; 12.8/1000 patient-years (95% CI 6.3-19.4) on ETN and 65.1/1000 patient-years (95% CI 48.4-81.8) on IFN. The risk was higher in the first than in the second year of treatment, but this difference was not statistically significant (p = 0.08) (38.9% of the SIs were recorded in the first 12 months of treatment). The risk of SI was significantly different among the three treatment groups (p<0.0001). Multivariate models confirmed that the use of steroids (p<0.046), concomitant DMARD treatment during anti-TNF therapy (p=0.004), advanced age at the start of anti-TNF treatment (p<0.0001), and the use of IFN or ADA rather than ETN (respectively p<0.0001 and p = 0.023) were strong and statistically significant predictors of infection. Conclusions: Anti-TNF therapy is associated with a small but significant risk of SI that is associated with the concomitant use of steroids, advanced age at the start of anti-TNF treatment, and the type of anti-TNF agent. (C) 2012 Elsevier B.V. All rights reserved.

****************************************************************************.

Objective The aim of the study was to retrospectively evaluate the long-term safety profile of anti-tumour necrosis factor (TNF)-α agents on the liver of patients with spondyloarthritis (SpA) and a previously resolved hepatitis B virus (HBV) infection. Methods Medical records from 992 consecutive outpatients receiving anti-TNF-α therapy between 2007 and 2015 were retrospectively reviewed. HBV infection was assessed evaluating HBV surface antigen (HBsAg), antibodies to HBsAg (anti-HBs), antibodies to hepatitis B core (anti-HBc), and HBV-DNA levels. In patients with a previously resolved HBV infection, serum levels of aminotransferase (AST/ALT) were also assessed every three months, while HBsAg and HBV-DNA every six months. Results We identified 131 consecutive patients (70 males, 61 females) with SpA and resolved HBV infection. At baseline none of the patients were positive for HBV-DNA, and AST/ALT levels were within the normal range with no subsequent increase during the observational treatment period. None received antiviral therapy prior to or during anti-TNF drug administration. At the end of the follow-up period (75.50±33.37 months) no viral reactivation was observed in anti-HBc positive patients, regardless of anti-HBs positivity. During the whole follow-up, HBV-DNA was undetectable in all patients, HBsAg remained negative, and it was not necessary to discontinue biologic therapy because of liver damage. Conclusion Our results confirm that pre-emptive antiviral prophylaxis may not be necessary routine, but strict monitoring for AST/ALT levels, as well as for changes in HBV serology and HBV-DNA remain necessary and seem a realistic and cost-effective approach to identify early viral reactivation. © Clinical and Experimental Rheumatology 2017.

tObjectives: The aim of this study was to assess whether body mass index (BMI) affects clinical outcomesin rheumatoid arthritis (RA) patients starting a second line biological drug after failure of a first TNF-blocker.Methods: From a longitudinal cohort, we analyzed 292 RA patients (66 obese, 109 overweight, and117 normal-weight) treated with a first ever anti-TNF- drug. Patients discontinuing the therapy werefollowed-up if began a second biological drug. Drug survival, by Kaplan-Meier life analysis, and 12 monthsdisease remission based on the 28-joint Disease Activity Score (DAS28) were assessed for either courseof biologics. The baseline predictors of clinical outcomes were assessed by Cox regression analysis.Results: Survival of the first anti-TNF- drug was lower in obese (39.4%) than in normal-weight (49.1%)patients, but the difference was not statistically significant. Obese patients had the highest hazard todiscontinue the first anti-TNF- drug (HR 1.64, 1.02–2.62 95% IC, P = 0.04), and the lowest percent-age of DAS28-based disease remission at 12 months (P = 0.04). In 97 (37 normal-weight, 36 overweight,24 obese) patients who started a second non-anti-TNF- biological drug, persistence on therapy wassignificantly lower in obese (43.5%) than in normal-weight (80%, P = 0.04) group, and again obesity sig-nificantly predicted drug discontinuation (HR 2.9, 1.08–8.45 95% IC, P = 0.04). Significantly, less obesepatients attained a disease remission (12%, P = 0.004) at 12 months.Conclusion: Our study provides evidence that obese RA patients poorly respond to second line non-anti-TNF- drugs after failure of a first TNF- inhibitor.

The recent availability of biosimilars as a result of the expiry of the patents of first-generation biotechnological drugs may theoretically reduce the direct costs of such treatments, making their use accessible to a larger number of patients. However, the currently available clinical data refer to a relatively small number of patients, and do not provide sufficient information concerning long-term efficacy and safety or the frequency of rare adverse events. Given the importance of the introduction of biosimilar drugs and the limitations of our current knowledge of their efficacy and safety profiles, we believe it is mandatory to draw up a position paper for Italian Rheumatologists. Moreover, in order to guarantee their safety, it is mandatory to indicate behavioural rules for the involved specialists and competent authorities, and perform ad hoc clinical trials and appropriate drug surveillance.

Clinical research is needed to identify patients with axial spondyloarthritis (axSpA) who are more likely to be responsive to interleukin (IL)-17 inhibition.

European and Asian studies report conflicting data on the risk of hepatitis B virus (HBV) reactivation in rheumatologic patients with a previously resolved HBV (prHBV) infection undergoing long-term biologic therapies. In this patient category, the safety of different immunosuppressive biologic therapies, including rituximab, was assessed. A total of 1218 Caucasian rheumatologic patients, admitted consecutively as outpatients between 2001 and 2012 and taking biologic therapies, underwent evaluation of anti-HCV and HBV markers as well as liver amino transferases every 3 months. Starting from January 2009, HBV DNA monitoring was performed in patients with a prHBV infection who had started immunosuppressive biologic therapy both before and after 2009. Patients were considered to have elevated aminotransferase levels if values were >1x upper normal limit at least once during follow-up. We found 179 patients with a prHBV infection (14 treated with rituximab, 146 with anti-tumor necrosis factor-alpha, and 19 with other biologic therapies) and 959 patients without a prHBV infection or other liver disease (controls). The mean age in the former group was significantly higher than the controls. Patients with a prHBV infection never showed detectable HBV DNA serum levels or antibody to hepatitis B surface antigen/hepatitis B surface antigen seroreversion. However, when the prevalence of elevated amino transferases in patients with prHBV infection was compared to controls, it was significantly higher in the former group only for aminotransferase levels >1x upper normal limit but not when aminotransferase levels >2x upper normal limit were considered. Conclusion: Among patients with a prHBV infection and rheumatologic indications for long-term biologic therapies, HBV reactivation was not seen; this suggests that universal prophylaxis is not justified and is not cost-effective in this clinical setting. (Hepatology 2015;62:40-46)

The prevalence of sarcopenia in rheumatic diseases has been evaluated in single diseases using various diagnostic approaches, generating conflicting data on the pathogenetic mechanism(s). Herein, we evaluated both muscle mass index (MMI) and muscle strength to assess sarcopenia and presarcopenia in patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), and ankylosing spondylitis (AS). Moreover, we evaluated the possible impact of disease/patient-related characteristics, therapeutic regimens, and nutritional aspects on sarcopenia. The present study included 168 patients of both genders, aged 40⁻75 years. All patients underwent a nutritional evaluation, physical activity level assessment, rheumatologic evaluation, and an MMI and muscle strength assessment. The prevalence of sarcopenia was about 20% in all the three rheumatologic diseases, whereas presarcopenia was significantly different in RA, PsA and AS (p = 0.006). At multivariate analysis, only age ≥60 years and the presence of a disability were associated with a significantly increased risk of sarcopenia (p = 0.006 and p = 0.01, respectively), while a higher C-reactive protein did not reach statistical significance. Sarcopenia is similar in RA, PsA and AS, whereas presarcopenia significantly differs in these three diseases. Disease activity/inflammation and nutritional aspects do not influence sarcopenia, while age ≥60 years and the presence of a disability significantly increase the risk of sarcopenia.

Serum amyloid-A (SAA) is an acute phase protein, synthesized by the liver and previously investigated as a marker of disease activity in many rheumatologic disorders. Its significance in Beh double dagger et's disease (BD), a chronic inflammatory disorder at the crossroad between autoimmune and autoinflammatory syndromes, is still unraveled. Our aim was to assess the role of SAA levels as a potential marker of disease activity in patients with BD. According to our findings, the occurrence of oral aphthosis, neurological impairment, and ocular disease is significantly associated with SAA serum levels higher than 30, 50, and 150 mg/L, respectively. We also suggest that increased SAA levels might identify a thrombotic risk in BD with previous or concurrent vascular involvement.

OBJECTIVE: T cell costimulation is a key point in the regulation of immune tolerance, immune response, and autoimmunity. T cell activation does not take place upon the simple engagement of T cell receptor; a second signal is needed to fully stimulate T cells. There are a variety of molecules that can act as costimulators, and among those CD28/CD80 signaling plays a crucial role in modulating T cell response. Cytotoxic T lymphocyte antigen-4, CD152 (CTLA4) is a physiologic antagonist of CD28, and abatacept, a synthetic analog of CTLA4, has recently been approved to treat rheumatoid arthritis. An abnormal T cell activation is also believed to sustain psoriatic disease both at skin and joint sites. We aimed to evaluate the rationale of blocking CD28/CD80 signaling and the possible use of abatacept for treating psoriatic arthritis (PsA). METHODS: We reviewed the role of CD28/CD80 signaling in promoting T cell inflammation in psoriasis and the effects of CTLA4 modulation in experimental models of psoriasis and in humans. RESULTS: CD28/CD80 seems to be crucial in stimulating T cell activation and inflammation in psoriasis, and its inhibition by CTLA4 analogs or by anti-CD28 blocking antibodies is effective against psoriasis. Few data are available on abatacept, which seems to be valuable for the treatment of PsA but less useful in the therapy of skin psoriasis. CONCLUSION: Although the CD28 molecule is crucial in activating T cells and inflammation in psoriasis, data on the efficacy of abatacept in the treatment of PsA are still not conclusive