Monica Todoerti

University of Pavia, Ticinum, Lombardy, Italy

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Publications (24)127.13 Total impact


    The Journal of Rheumatology 10/2015; 42(10):1993-1994. DOI:10.3899/jrheum.150230 · 3.19 Impact Factor
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    ABSTRACT: Background Actually, as suggested from current therapeutic guidelines, tapering of biologic agents (bDMARDs) seems a feasible option in subsets of rheumatoid arthritis (RA) patients in persistent clinical disease control [1]. However definite step-down schedules are far to be fully elucidated due to the heterogeneity of available data in controlled trials. Data on real life contests are even fewer. Objectives To analyze the feasibility of bDMARD spacing in maintaining clinical disease control in real life RA patients in persistent low disease activity (LDA) or remission. To monitor sub-clinical signs of disease activity during bDMARDs tapering. Methods RA patients in persistent clinical disease control (at least LDA according to DAS28 score for at least 6 months) underwent current bDMARD (anti-TNF/no anti-TNF agents for at least 1 year) spacing (doubling of the inter-administration time); concomitant co-medications (conventional synthetic DMARDs/csDMARDs and/or low dose oral corticosteroids/CS) were carried on at stable dosages. Clinical and ultrasonographic (US) assessments were performed bi-monthly over initial 6 months period in order to define clinical relapse (> LDA) and to monitor clinical and sub-clinical signs of inflammation (Gray scale, GS, and power Doppler, PD scores detected on hand and wrist US examination). Results about first 4 months of follow up are yet available for preliminary analysis. Results Globally, 35 patients met the criteria and agreed to the spacing. Most of them had an established disease (mean duration ± sd 11,92±7,80 years) with markers of poor prognosis (57% seropositive patients, 60% patients with erosive disease). They were generally on their first anti-TNF bDMARD therapy (30 anti-TNF, 4 tocilizumab, 1 abatacept) together with csDMARDs co-medication (29/35 patients); they were mostly CS free (28/35 cs-free patients; 7 patients on low dose oral CS). Over 4 months of observation DAS28 score did not significantly change (mean value ± sd from 1,92±0,59 to 1,89±0,63, p not significant), as happened for GS score (median [IQR] from 9 [8-12] to 11 [9-13], p not significant). Median PD score [IQR] significantly increase over time, from 0 [0-0] at baseline examination to 1,5 [0-4] (p=0,01) at 4 months. In 4 months, globally 2 patients relapsed. Conclusions Biologic DMARDs spacing might be a possible therapeutic option in real life RA patients in persistent disease control: despite the substantial increase in PD score, few patients clinically relapsed in the first months of observation. For a complete evaluation, risk-to-benefit issues should involve long-term clinical, functional and structural outcomes, along with safety and financial issues too. Predictive factors need to be fully elucidated to target patients who might benefit more from this strategy. References Disclosure of Interest None declared
    Annals of the Rheumatic Diseases 06/2015; 74(Suppl 2):1036.3-1037. DOI:10.1136/annrheumdis-2015-eular.4942 · 10.38 Impact Factor
  • S. Monti · S. Breda · F. De Nard · V. Grosso · M. Todoerti · C. Montecucco · R. Caporali ·
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    ABSTRACT: Background Treating disease to target is emerging as the recommended strategy also in the management of axial-SpA (axSpA) (1). Reaching remission, defined as inactive disease (ID), constitutes the ideal target in clinical practice. Objectives Using the new composite disease activity index “Ankylosing Spondylitis Disease Activity Score” (ASDAS) (2) we assessed the prevalence of ID in a cohort of patients with axSpA treated with anti-TNFα agents. Potential patient- and disease-related factors influencing the status of ID were analyzed. Methods The study population was selected from outpatients with axSpA treated with anti-TNFα attending our Rheumatology Department. Disease activity was evaluated in terms of BASDAI and ASDAS-CRP during the latest follow up visit. ID was defined as ASDAS-CRP<1.3 (2). Statistical analysis was performed with STATA. Results General characteristics of the 53 enrolled patients are presented in Table 1. A BASDAI <4 was recorded for 70% of the study population, while only 31% showed ID according to ASDAS-CRP (Figure 1). As expected, a strict correlation between the two disease activity indices was confirmed (Spearman's r =0.76; p<0.0001). Multivariate logistic regression demonstrated an inverse correlation of ID status with NSAIDs intake (OR 0.15; CI95% 0.45-0.54). ID achievement resulted independent from sex, disease duration, BASMI,DMARDs, type of anti-TNFα agent. Conclusions In our cohort of axSpA treated with biological agents, only one third achieved ID according to ASDAS-CRP. Even with the limitations of the small sample size, ID does not correlate with the principle patient- and disease-related features but is inversely associated with NSAIDs intake. Further studies are needed to optimize the targeted treatment of axSpA and to identify potential predictive factors of ID. References Disclosure of Interest None declared
    Annals of the Rheumatic Diseases 06/2015; 74(Suppl 2):1162.2-1163. DOI:10.1136/annrheumdis-2015-eular.6055 · 10.38 Impact Factor
  • S. Monti · M. Todoerti · L. Cavagna · V. Codullo · C. Montecucco · R. Caporali ·
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    ABSTRACT: Background The treatment of Behçet disease (BD) is still largely based on the evidence driven from few randomized controlled trials (RCTs), case series and off label use of biologic agents (1). Objectives To determine disease characteristics and treatment strategies, with particular focus on the indications, outcomes and safety of biologic therapy, in a cohort of patients with BD. Methods Patients with a diagnosis of BD were recorded in a database since diagnosis and followed until the latest follow up visit, analyzing disease flares and therapeutic strategies adopted. All patients provided written informed consent. Results A total of 79 patients were included. General characteristics of the study population are presented in table 1. The most frequent disease manifestations were mucosal (100%), cutaneous (67.09%) and musculoskeletal involvement (62.02%). 11 patients (13.9%) were treated with biologic agents. All patients experienced non-biologic therapy before starting a TNF-inhibitor (TNFi) agent. The preferred first-line TNFi was infliximab (n=6), followed by adalimumab (n=3) and etanercept (n=1). The most frequent indications for biologic step up therapy were untreatable mucosal ulcers and arthritis (n=6), neurological involvement (n=2), refractory uveitis (n=1) and intestinal involvement (n=1). Most patients initiated a biological treatment within the first year of follow up. TNFi were more frequently prescribed in combination with methotrexate or azathioprine. 7 patients switched to a second TNFi (adalimumab n=4, infliximab n=2, or etanercept n=1) because of inefficacy of the first biologic agent (n=6) or safety issues (recurrent infections; n=1). The main reason for switching to a different biologic agent was refractory arthritis and mucocutaneous involvement. Only 1 patient was treated with three different TNFi because of a particularly aggressive musculoskeletal involvement. Rituximab (500 mg prescribed once a week for 4 infusions to be repeated after at least 6 months) was successfully used in one patient with recurrent pancytopenia, allowing complete and long-standing remission after 8 therapeutic cycles. The off label prescription of biologic agents did not raise any safety or tolerability issues in our cohort of BD patients and allowed for a 90.91% remission rate by the time of the latest follow up visit. Conclusions A relevant proportion of patients in our BD cohort required to be treated with biological agents, mainly because of mucocutaneous, musculoskeletal or neurological disease manifestations. Off label use of biologic agents was generally effective and safe. Further studies are needed to define a dedicated and patient-tailored therapeutic approach. References Disclosure of Interest None declared
    Annals of the Rheumatic Diseases 06/2015; 74(Suppl 2):1120.3-1121. DOI:10.1136/annrheumdis-2015-eular.5127 · 10.38 Impact Factor
  • V. Grosso · F. De Nard · S. Breda · S. Monti · M. Todoerti · R. Caporali · C. Montecucco ·
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    ABSTRACT: Background Many patients with rheumatoid arthritis (RA) experience anxiety and depression, with higher presence of these disorders in those with poorer outcome [1]. Previous experiences found relationships with psychological status and disease activity in patients with active disease [2,3]. Further evidences are needed to asses the impact on residual RA activity during treatment. Objectives To register the prevalence of anxious (ANX) and depressive (DEP) disorders in RA patients treated with bDMARDs with stable disease and therapy and to evaluate their connection with disease activity. Methods We assessed the presence of ANX and DEP disorders with the HADS questionnaire [4] in patients with RA treated according the EULAR 2013 recommendations with bDMARDs [5]. We registered disease activity using DAS28 score during the same day of questionnaire compiling. Patients with major changes in their DMARD therapy during the previous six months, with known diagnosis of anxiety-depressive syndrome, fibromyalgia, or treated with antidepressant drugs were excluded. The variables of interest were compared between groups with Kruskall-Wallis test. Results We assessed 200 patients, female 171 (85%), with an overall median (IQR) age and disease duration of 62,35 (54,09 – 76,03) years and 11,24 (7,29 – 19,46) years respectively. At least one ANX or DEP disorder was present in 93 (46.5%) patients. In patients with ANX, DEP and with ANX*DEP disorders values of pain VAS, DAS28, GH, PGA, number of painful joints on 28 (TND28), HAQ were higher than those in HEALTY group (p<0,01). Prednisone dosage was higher among patients with ANX or DEP disorders. Number of swollen joints on 28 (SWJ28) CRP and ESR were not different among groups. There was a moderate correlation between HADS scores and DAS28, pain VAS, PGA, GH and TND28. Conclusions There is a high prevalence of ANX and DEP disorders in patients with RA. Patients with those disorders have higher level of residual disease based on higher subjective variables, while objective variables (SWJ28 and laboratory indexes) remain unmodified. The higher steroid doses in patients with ANX or DEP are probably due to higher disease activity measured with DAS28. References Disclosure of Interest None declared
    Annals of the Rheumatic Diseases 06/2015; 74(Suppl 2):1027.2-1027. DOI:10.1136/annrheumdis-2015-eular.3290 · 10.38 Impact Factor
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    ABSTRACT: Hepatitis B virus (HBV) reactivation in rheumatoid arthritis (RA) patients undergoing biological therapy is not infrequent. This condition can occur in patients with chronic hepatitis B as well as in patients with resolved HBV infection. Current recommendations are mainly focused on prevention and management strategies of viral reactivation under tumor necrosis factor-α inhibitors or chimeric monoclonal antibody rituximab. In recent years, growing data concerning HBV reactivation in RA patients treated with newer biological drugs like tocilizumab and abatacept have cumulated. In this review, epidemiology, pathogenesis and natural history of HBV infection have been revised first, mainly focusing on the role that specific therapeutic targets of current biotechnological drugs play in HBV pathobiology; finally we have summarized current evidences from scientific literature, including either observational studies and case reports as well, concerning HBV reactivation under different classes of biological drugs in RA patients. Taking all these evidences into account, some practical guidelines for screening, vaccination, prophylaxis and treatment of HBV reactivation have been proposed.
    World Journal of Hepatology 03/2015; 7(3):344-61. DOI:10.4254/wjh.v7.i3.344
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    ABSTRACT: At present, growing scientific evidence from the medical literature and expert opinion provides strong consideration for a mandatory role of glucocorticoids (GCs) in the management of rheumatoid arthritis (RA). Earlier application strategies were based on initial high doses, with subsequent tapering schedules, resulting in dose-related side effects. Recent low-dose GC schemes are more feasible in routine care, while providing evidence of clinical, functional and structural efficacy. Thus, initial low-dose GC 'bridging' treatment on a disease-modifying antirheumatic drug background should be included in any existing recommendations for RA management, as very recently advocated by the EULAR Task Force 2013 updated guidelines. Long-term low-dose therapy appears to provide acceptable safety, leading to long-standing slowing of structural damage, seen even after GC therapy withdrawal. Gaps in knowledge about the optimal method to taper and possibly discontinue GC treatment remain, and this topic should be addressed in clinical trials and observational studies. Recent efforts in GC medication have also included the introduction of a modified-release drug formulation capable of drug delivery consistent with chronobiological pathogenetic rhythms of disease, which has been quite efficacious in controlling the signs and symptoms related to pathways of circadian cytokines. Long-term data will further clarify the add-on benefits of such modified-release formulations. © 2014 S. Karger AG, Basel.
    NeuroImmunoModulation 09/2014; 22(1-2):104-111. DOI:10.1159/000362730 · 1.88 Impact Factor
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    ABSTRACT: Background Rituximab (RTX), a chimeric monoclonal antibody targeting CD20 B cell antigens, is a safe and effective treatment for rheumatoid arthritis (RA) [1]. It has been approved for RA patients who have inadequately responded to one or more anti-TNF agent and has recently been demonstrated to be significantly more effective after a first anti-TNF than switching to a second [2]. Long-term extensions of randomised controlled trials have demonstrated that prolonged RTX exposure of up to 9.5 years does not affect its safety, but there are no data concerning real-life clinical experience. Objectives The aim of this multicentre clinical study was to evaluate the retention of RTX treatment in patients with RA. Methods The clinical records of 472 RA patients treated with RTX from August 2006 to December 2013 in ten Italian rheumatology centres were reviewed, and treatment survival and the impact of selected variables were evaluated using Kaplan-Meier and Cox survival analyses. Results Four hundred and seventy-two patients with a diagnosis of RA based on the 1987 ACR classification criteria (81.6% female; mean age 56.2±12.8 years; mean disease duration 10.5±8 years; 76.3% RF positive; 75% anti-CCP positive) were treated with RTX for a mean of 40.1±26.37 months (range 0-122). Seventy-six percent were co-treated with MTX, and 24% had previously received two or more anti-TNF agents. Their median DAS28 score at baseline was 5.07±1.3. For patients completing at least 12, 24, 36, 48 and 60 months of follow-up, the retention rates were respectively 87.9%, 78.8%, 72.5%, 67.6% and 63.8% (Fig. I) Treatment discontinuations because of adverse events and inefficacy had a similar temporal trend. Multivariate analysis (Cox regression) showed that none of the considered predictive variables was significantly associated with treatment survival: gender p=0.399; age p=0.486; disease duration p=0.999, baseline DAS28 p=0.412; number of previous anti-TNFα failures p=0.975; the presence of RF p=0.513; MTX treatment p=0.340. Conclusions Our findings show that 63.8% of RA patients continued treatment with RTX for 60 months. References Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.3994
    Annals of the Rheumatic Diseases 06/2014; 73(Suppl 2):491-491. DOI:10.1136/annrheumdis-2014-eular.3994 · 10.38 Impact Factor
  • F. De Nard · M. Todoerti · V. Grosso · S. Rossi · R. Caporali · C. Montecucco ·
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    ABSTRACT: Background HBV infection represents a major issue in RA patients undergoing biological disease-modifying anti-rheumatic drugs (bDMARDs) treatment (1). While several studies deal with the risk of hepatitis reactivation under anti-TNF agents, there is limited experience with newer drugs as tocilizumab (TCZ) and abatacept (ABA) (2). Objectives To assess the risk of hepatitis B reactivation in real-life RA patients undergoing treatment with ABA and TCZ. Methods RA patients with a history of HBV infection (“HBV chronic inactive carriers” with HBsAg+ and undetectable or <2,000 IU/mL viral load + normal liver function tests and “occult carriers” with only HBcAb+) and treated with ABA or TCZ have been retrospectively analyzed for the risk of “viral re-activation” (increase in HBV DNA>1 log10 IU/mL or detection of previously undetected HBV DNA) and/or “viral hepatitis B” (increase in aminotransferases, increase in serum HBV-DNA, presence of necroinflammation and/or fibrosis in liver biopsy) by regularly detecting HBsAg, HBV viral load, aminotransferases throughout follow-up visits (at 6,12 and 18 months). Results Out of 125 RA patients consecutively treated with ABA or TCZ at a single center, 17 (13,6%) were HbcAb-pos: 16 occult carriers (8 treated with ABA+8 with TCZ), and 1 chronic inactive carrier treated with ABA. Patients were followed for a median (IQR) of 1.2 (0.7-1.5) years. They were previously treated with a median (IQR) number of 1 (1-2) synthetic DMARDs (sDMARDs) and 0 (0-1) bDMARDs. The mean age (sd) was 54.7 (16.3) years, the median disease duration was 5.8 (1.8-7.5) years. Most patients in both groups were treated with concomitant methotrexate (8/9 in the ABA, 5/8 in the TCZ group) and low dose corticosteroids. In the ABA group, 1 patient with comorbid HCV chronic infection (HCV-RNA+) started lamivudine for aminotransferases elevation (less than 2-fold ULN) occurring 2 months after ABA initiation, with a gradual amelioration of lab levels along with undetectable viral load throughout the follow-up. 2 patients (1 occult carrier and 1 chronic inactive carrier) underwent lamivudine before ABA with no adverse events related to HBV, whilst among the other 6 patients not receiving antiviral prophylaxis only 1 experienced positivization of viral load under the cut-off limit for viral reactivation (85 UI/mL) without aminotransferases elevation at 12 months. In the TCZ group, no patient received antiviral prophylaxis without hepatitis B reactivation. Conclusions Despite limited to few patients and short follow-up, use of ABA and TCZ in RA patients with past history of HBV infection (chronic inactive/occult carrier) seems safe. However, periodic monitoring of liver function tests and viral load is mandatory. Viral prophylaxis might be considered mainly in patients undergoing ABA, according to scientific literature too. Further data are needed to fully clarify long-term safety issues. References Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.5021
    Annals of the Rheumatic Diseases 06/2014; 73(Suppl 2):499-499. DOI:10.1136/annrheumdis-2014-eular.5021 · 10.38 Impact Factor

  • Annals of the Rheumatic Diseases 06/2014; 73(Suppl 2):400-401. DOI:10.1136/annrheumdis-2014-eular.4432 · 10.38 Impact Factor
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    ABSTRACT: In the last 10 years, the growing approval and marketing of biological agents has significantly ameliorated the outcomes of rheumatoid arthritis and spondyloarthritis patients suffering from active and refractory disease despite conventional treatments. As patent protection of many biopharmaceuticals will expire in the next years, biosimilars could be proximally introduced. Such agents could be marked only when they will be proven, through in vitro and in vivo studies, to be similar enough to the original comparator in term of quality, efficacy and safety. As biosimilars are less expensive than corresponding originators, a wider use of these drugs may substantially cut off the expenditure of biopharmaceuticals. Nevertheless, ongoing debate exists in scientific community: the intrinsic complex and large structure of biologic molecules besides the natural variability in the manufacturing processes might lead to a slightly different product respect to the original one, so that relevant implications for efficacy and safety concerns might arise, especially in the long-term period. Immunogenicity and extended indications of biosimilars represent further matter of discussion, too. Thus, before their approval and marketing, specific guidelines and steps imposed by national and/or international regulatory agencies should be followed along with the respect of scientific societies position in each specific contest.
    06/2014; 6(1). DOI:10.4081/rr.2014.5518
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    ABSTRACT: Background Rituximab (RTX), an anti-CD20 monoclonal antibody, is an effective treatment for Rheumatoid arthritis (RA), targeting B cells. However, the safety of this drug in hepatitis B surface antigen (HBsAg) negative/anti-hepatitis B core antigen (anti-HBc) positive carriers is still unknown. The purpose of our study is to evaluate the risk of HBsAg seroreversion in this kind of patients. Objectives The purpose of our study is to evaluate the risk of HBsAg seroreversion in this kind of patients. Methods We retrospectively reviewed 310 RA patients treated in 5 italian outpatient rheumatologic Clinics with RTX from August 2006 to December 2011. 35 (11,2%) were HBsAg negative/anti-HBc positive patients and they did not undergo antiviral prophylaxis. Complete serological panel for HBV status before starting RTX infusions and adequate post-treatment follow-up were available. All patients (75% female, median age 60 years, median disease duration 8 yrs, 100% serum HBV DNA negative by sensitive PCR assay, 87% anti-HBs positive) has been treated with one or more disease-modifying anti-rheumatic drugs (83% MTX, 26% CYS, 80% PDN, 8% LEF, 6% AZA) and were eligible for RTX therapy according to international guidelines. The median period of RTX administration was 3 cycles (range: 1-8) and the therapy was ongoing at the end of observational period in 76% of cases. All patients were laboratory and clinically evaluated every three months. Serum HBsAg and serum HBV DNA were assessed in all patients every 6 months or in case of alanine aminotransferase (ALT) elevation and at the end of the follow-up period. Results The median follow-up time was 45 months (range: 12-80). In this period 27% of patients had anti-HBs titer decrease (2 patient with a complete lost of anti-HBs levels). Only one patient (3%) had an increase of serum HBV DNA (from undetectable to 24 and 44 IU/mL, 1 week apart) without either HBsAg seroreversion or ALT increase. This virological breakthrough occurred 5 months after the first cycle of RTX and required Lamivudine treatment which successfully suppressed viral replication in 4 weeks. One patient (3%) had an ALT flare, not related to HBV reactivation. Conclusions The retrospective review of our multicentre experience suggest that an adequate monitoring of HBsAg and HBV DNA levels in RA patients HBsAg negative/anti-HBc positive, as recommended by international guidelines, allows us to avoid the antiviral prophylaxis during RTX treatment. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.2656
    Digestive and Liver Disease 02/2014; 46(1):e23. DOI:10.1016/j.dld.2014.01.053 · 2.96 Impact Factor
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    ABSTRACT: Background Pharmaco-epidemiological studies on TNF-inhibitors (TNF-I) in rheumatoid arthritis (RA) and spondyloarthritis (SpA) are providing useful data about effectiveness and safety in clinical practice. Objectives To compare drug survival in RA and SpA according to TNF-I drug using data from a multicentre Italian cohort study. Methods The patients were selected from the Monitornet database, a prospective cohort study to monitor the long-term safety of biologic therapy involving 27 rheumatology centres across Italy, supported by the Italian regulatory agency AIFA. For the purpose of these analyses we included RA or SpA patients, who started a first course infliximab (INF), etanercept (ETA) or adalimumab (ADA). Drug survival was primarily defined from start until first discontinuation (overall drug survival) and secondarily due to ineffectiveness or adverse events (AEs). A first set of analyses assessed the relationship between diagnosis and drug survival using RA as reference category, adjusting for age, gender and comorbidities. A second set of analyses stratified by diagnosis explored the relationship between TNF-I and drug survival using INF as reference category, adjusting for age, gender, comorbidities, disease duration, previous DMARDs, calendar, baseline CRP, disease activity (DAS28 or BASDAI) and severity (HAQ score or BASFI). Drug survival was analyzed using Cox proportional hazards models. Results are presented as hazard ratios (HR) and 95% confidence intervals (CI). Results 1992 RA patients (79.8% women, mean age 55.5 yrs (SD 12.3), mean disease duration 9.6 yrs (SD 8.0), mean baseline DA28 4.4 (SD 1.9), baseline HAQ 1.4 (SD 0.7), median number of previous DMARDs 2 (IQR 1-3) and 993 SpA patients (55.2% men, mean age 49.6 yrs (SD 12.5), mean disease duration 6.9 yrs (7.5), mean baseline BASDAI 4.7 (SD 2.4), mean baseline BASFI 4.6 (SD 2.5) were included in the analyses. 44.2% RA patients started ETA, 21.4% INF, 34.4% ADA, while 45.8% SpA patients ETA, 22.3% INF, 31.9% ADA. Using RA as reference, SpA patients showed a lower drug discontinuation (HR 0.92 [95%CI 0.87, 0.99]), due to a lower withdrawal for inefficacy (HR 0.90 [95%CI 0.82, 0.99]). Both in RA and in SpA, compared to INF, ETA showed a slightly better survival on treatment, also due to lower discontinuation for inefficacy (see table). Conclusions These data support a better survival on treatment for SpA over RA and for ETA as compared with INF, mainly due to lower discontinuation for ineffectiveness rather than for AEs. Disclosure of Interest None Declared
    Annals of the Rheumatic Diseases 01/2014; 71(Suppl 3):370-370. DOI:10.1136/annrheumdis-2012-eular.2629 · 10.38 Impact Factor

  • Clinical and experimental rheumatology 01/2014; 32(5):788. · 2.72 Impact Factor
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    ABSTRACT: The objective of this review is to update the recommendations of the 2010 Italian Consensus on the use of methotrexate (MTX) in rheumatoid arthritis (RA) and other rheumatic diseases. The literature published between 2008 and 2012 was systematically reviewed and updated recommendations on MTX use in rheumatic diseases, particularly RA, were formulated. These recommendations were approved by a panel of expert Italian Rheumatologists. A total of 10,238 references were identified, among which 70 studies were selected for critical evaluation. Sufficient evidence had accumulated to warrant changes to several of the recommendations in the new version. A new recommendation for patients with RA who are in MTX-induced clinical remission was also proposed and approved by the panel. Updated recommendations for the use of MTX in patients with RA or other rheumatologic disease are proposed.
    Reumatismo 12/2013; 65(5):207-18. DOI:10.4081/reumatismo.2013.207
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    ABSTRACT: In rheumatoid arthritis (RA), low-dose glucocorticoid (GC) therapy has a well-established effect on disease activity. Particularly in early RA, robust evidence demonstrates that GC treatment in association with standard disease-modifying anti-rheumatic drugs (DMARDs) is effective in inducing high remission rates, earlier and more persistently. Despite international recommendations that discourage long-term concomitant GC use, the majority of the clinical trials and observational registries on biologic agents include a high proportion (up to 80%) of patients in treatment with GC. From an analysis of the literature, a substantial lack of reliable information about the efficacy of GC in association with biologic agents emerges; in particular, the role of GC co-therapy in sustaining remission after biological therapy discontinuation remains to be clarified. Given the increasing prevalence of patients in sustained remission, a rational discontinuation strategy should include low-dose GCs in the experimental design to elucidate their role in inducing and maintaining biologic-free remission, for efficacy, safety and pharmacoeconomic considerations.
    Clinical and experimental rheumatology 10/2013; 31(4 Suppl 78):S9-13. · 2.72 Impact Factor
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    ABSTRACT: To compare drug survival of different anti-TNF drugs (infliximab, INF, etanercept, ETA, and adalimumab, ADA) in rheumatoid arthritis (RA) and spondyloarthritis (SpA) by analysing data collected from an Italian multicenter observational cohort study. All patients with RA or SpA registered in the MonitorNet database who started their first course of anti-TNF therapy were included. Overall drug survival was measured, along with specific reasons of discontinuation (inefficacy or adverse events). A first set of analyses using RA as reference category assessed the relationship between diagnosis and drug survival. A second set of analyses stratified by diagnosis (RA and SpA) used INF as reference drug. Adjustment for confounders was performed. The results are presented as adjusted hazard ratios (adjHR) and 95% confidence intervals (95%CI). 2640 RA patients and 1220 SpA patients with a median follow-up of 17 months (IQR 7.2-33.4) were included in the analyses. Patients with a diagnosis of SpA showed a lower risk of drug discontinuation with an adjHR (95%CI) of 0.81 (0.73, 0.90). In SpA, the subset of patients with ankylosing spondylitis (AS) showed the best survival on treatment. In RA, both ETA and ADA showed a significantly lower probability of withdrawal when compared to INF [adjHR (95%CI) 0.46 (0.38, 0.56) and 0.68 (0.57, 0.81), respectively]. Similar results were found in SpA. Drug survival for SpA is longer than that in RA mainly due to the AS subgroup. In both RA and SpA, ETA and ADA showed a better retention on treatment when compared to INF.
    Clinical and experimental rheumatology 08/2013; 31(6). · 2.72 Impact Factor
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    ABSTRACT: Interest in the numerous benefits of corticosteroid medication in the management of rheumatoid arthritis (RA) goes back to the mid-1950s, and has recently been renewed. The established evidence of their rapid symptomatic effects, along with the growing recognition of their long-lasting disease-modifying properties and preliminary data about their sub-clinical action, led us to reconsider the potential of corticosteroids in the treatment of RA, given their acceptable safety profile, especially when used at low dosages. Over time, several corticosteroid-based therapeutic approaches have been explored in order to optimize their clinical benefits, while limiting the adverse effects. Clinical data reported with initial high-dosage corticosteroid schedules with subsequent step-down schemes suggest clinical efficacy, but are not applicable to patient management in a real-life setting. Encouraging results on the clinical and sub-clinical effects of low dosages have led to a shift in usual daily practice. We present past and recent efforts to clarify the role of corticosteroids in the treatment of RA, focusing on the best approach in terms of dose and timing of corticosteroid administration. Additional information about different routes of administration, step-down schedules and adverse effects are also considered.
    Drugs 01/2013; 73(1). DOI:10.1007/s40265-013-0008-4 · 4.34 Impact Factor
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    ABSTRACT: In early rheumatoid arthritis (RA), low-dose oral prednisone (PDN) co-medication yields better clinical results than monotherapy with disease-modifying anti-rheumatic drugs (DMARDs). In addition, ultrasonography (US) evaluation reveals rapid and significant effects of glucocorticosteroids on subclinical synovitis. No data currently exist that examine the clinical and US results offered by glucocorticoid co-medication over DMARD monotherapy in early RA patients. Two hundred and twenty patients with early RA (< 1 year from clinical onset) were treated according to a low disease activity (LDA) targeted step-up protocol including methotrexate (MTX) and, in the active treatment arm, low-dose (6.25 mg/day) oral PDN over 12 months. Clinical disease activity measures were collected at baseline, 2, 4, 6, 9 and 12 months, and US examination of hands was performed at baseline, 6 and 12 months. Grey-scale and power Doppler (PD) synovitis were scored (0 to 3) for each joint. At 12 months, clinical remission according to the disease activity score among 28 joints was defined as the clinical outcome, and a total joint PD score of 0 (PD negativity) as the imaging outcome. Each group included 110 patients with comparable demographic, clinical, laboratory and US characteristics. At 12 months, the LDA rate was similar in the two groups, whilst the clinical remission rate (risk ratio = 1.61 (95% confidence interval = 1.08, 2.04)) and PD negativity rate (risk ratio = 1.31 (95% confidence interval = 1.04, 1.64)) were significantly higher in the MTX+PDN group. In early RA, despite a similar response rate in terms of LDA, low-dose oral PDN co-medication led to a higher proportion of clinical remission and PD negativity compared with MTX monotherapy, thus ensuring a better disease activity control. Current Controlled Trials ISRCTN2486111.
    Arthritis research & therapy 05/2012; 14(3):R112. DOI:10.1186/ar3838 · 3.75 Impact Factor
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    ABSTRACT: Biological markers specifically reflecting pathological processes may add value in the assessment of inter-individual variations in the course of rheumatoid arthritis (RA). The current study was undertaken to investigate whether baseline serum levels of the chemokine CXCL13 might predict clinical and ultrasonographic (US) outcomes in patients with recent-onset RA. The study included 161 early RA patients (disease duration < 12 months) treated according to a disease activity score (DAS) driven step-up protocol aiming at DAS < 2.4. Clinical disease activity measures were collected at baseline, 2, 4, 6, 9 and 12 months, and US examination of the hands was performed at baseline, 6 and 12 months. Grey-Scale (GS) and Power Doppler (PD) synovitis were scored (0 to 3), with overall scores as the sum of each joint score. CXCL13 levels were measured at baseline by enzyme-linked immunosorbent assay and evaluated in relation to the achievement of low disease activity (LDA, DAS < 2.4) and US residual inflammation (PD ≤ 1) at 12 months. Baseline levels of CXCL13 were significantly higher in RA compared to healthy controls (n = 19) (P = 0.03) and correlated with measures of synovitis, such as the swollen joint count (R 0.28, P < 0.001), the US-GS (R 0.27, P = 0.003) and US-PD (R 0.26, P = 0.005) score. Although CXCL13 did not predict the likelihood of achieving clinical LDA at 12 months within a structured treat-to-target protocol, elevated levels of CXCL13 were associated with more frequent increases of methotrexate dosage (P < 0.001). Using adjusted analyses, the highest levels of CXCL13 (> 100 pg/ml) were the only independent predictor of residual imaging inflammation (P = 0.005), irrespective of initial US-PD scores, disease activity status, acute phase reactants and autoantibodies. Among the patients in clinical LDA at 12 months, US-PD scores ≤ 1 were less frequently achieved in the high baseline CXCL13 (> 100 pg/ml) group, with an adjusted OR = 0.06 (95% CI 0.01 to 0.55, P = 0.01). CXCL13 emerges as a new biological marker in early RA, accurate in assessing the severity of synovitis and the persistence of US-PD activity over time in response to conventional treatments.
    Arthritis research & therapy 02/2012; 14(1):R34. DOI:10.1186/ar3742 · 3.75 Impact Factor

Publication Stats

226 Citations
127.13 Total Impact Points


  • 2009-2015
    • University of Pavia
      • Department of Diagnostic, Paediatric, Clinical and Surgical Science
      Ticinum, Lombardy, Italy
  • 2012-2014
    • Policlinico San Matteo Pavia Fondazione IRCCS
      • s.c. Cardiologia
      Ticinum, Lombardy, Italy