Search

Background Based on current evidence, recent guidelines of the National Institute of Health, USA indicated the use of remdesivir and dexamethasone for the treatment of COVID-19 patients with mild-moderate disease, not requiring high-flow oxygen. No therapeutic agent directed against the immunologic pathogenic mechanisms related to the cytokine release syndrome complicating the disease was indicated. Objectives The purpose of this review was to assess the clinical impact of different therapies for COVID-19; thus, helping to identify the optimal management of the disease. To explain the rationale for the different therapeutic approaches, the characteristics of SARS-CoV-2, the pathogenesis of COVID-19, and the immune response triggered by SARS-CoV-2 infection were reported. Methods The efficacy assessment of the different treatments was performed by a systematic review in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Available English language published articles including randomised controlled trials, open-label trials of antivirals and immune therapies extracted from Medline, Google Scholar, and MedRxiv databases were analysed. For inclusion, the primary end point of the trials had to be the efficacy as measured by the improvement of clinical features, or mortality, or the Intensive Care Unit Admission rate, or the discharge number. Case reports, paediatric studies, and studies without control group were excluded. The literature search was extended up to August 15, 2020. Results After the removal of duplicate articles, and the exclusion of studies not meeting the eligibility criteria, 2 trials of lopinavir/ritonavir, 1 of favipiravir, 3 of remdesivir, 1 of dexamethasone, 3 of hydroxychloroquine, 2 of colchicine, 6 of tocilizumab, 1 of sarilumab, 1 of siltuximab, 2 of anakinra, 3 of baricitinib, 1 of ruxolitinib, 1 of mavrilimumab, and 1 of itolizumab were suitable for the review. Among antivirals, only remdesivir significantly reduced the time to recovery, and mortality. Data for chloroquine and hydroxychloroquine were largely inconclusive. In a large trial, dexamethasone 6 mg/day reduced mortality by one-third. Trials of tocilizumab and sarilumab did not definitively demonstrate efficacy. Anakinra significantly reduced the mortality in 2 trials. Three retrospective trials on a cumulative number of 145 patients, reported the efficacy of baricitinib, with significant reduction of intensive care unit admission, and deaths. These results were recently confirmed by the ACTT-2 trial. Due to paucity of studies and to the small size clinical series, the results of other immune therapies were not conclusive. Conclusions Beyond the supportive therapy, up to now the best therapeutic approach for COVID-19 may be a three-step combination therapy, including remdesivir 100 mg/day (200 mg loading dose on first day) in the first stage of the disease, and combined dexamethasone 6 mg/day plus baricitinib 4 mg/day to target the immune dysregulation triggered by the SARS-CoV-2 infection. The promising results of anakinra should be confirmed by the ongoing RCTs. Electronic supplementary material The online version of this article (10.1007/s40265-020-01421-w) contains supplementary material, which is available to authorized users.

Highlights • Baricitinib, an anti-JAK1/JAK2, reduces cytokine release and SARS-Co-V2 entry. • In a retrospective multicenter study baricitinib reduces COVID-19 mortality rate. • Baricitinib reduces intensive care unit admissions of COVID-19 pneumonia. • Baricitinb reduces SARS-CoV-2 viral burden detected by nasopharyngeal swab. • Baricitinib used for 2 weeks was not associated with serious adverse events., Graphical abstract Image, graphical abstract

Janus kinases inhibitors (anti-JAKs), including tofacitinib, baricitinib, upadacitinib, and filgotinib, represent a new class of synthetic targeted drugs for the treatment of rheumatoid arthritis (RA). In this review, the risk of active tuberculosis (TB) occurrence in patients receiving anti-JAKs was assessed. The literature on this topic, updated to 29 February 2020 was reviewed. Overall, 40 reports (22 tofacitinib, 10 baricitinib, 5 upadacitinib, 3 filgotinib) were examined. A low frequency, not exceeding 0.25%, of active TB cases in patients were exposed to anti-JAKs. Only 1 of 89 recorded cases in tofactinib and baricitinib exposure occurred in countries at intermediate or high TB risk, and most of the cases probably were due to first mycobacterium tuberculosis (Mtb) exposure. Although no cases were observed in patients receiving upadacitinib and filgotinib, long-term trials and data from real-life are required to more precisely address the TB risk associated with the two drugs.Discussion on the TB risk associated with anti-JAKs, and on the need for accurate evaluation of host-related risk factors in high risk countries.Available data on anti-JAKs suggest a negligible risk of active TB occurrence in low endemic areas.

In 2015, the Italian board for the TAilored BIOlogic therapy (ITABIO) proposed evidence-based decisional statements for first-line tailored biologic therapy in patients with rheumatoid arthritis (RA). Taking into account the new licensed drugs, the aim of the present review was to update the previous statements.A narrative review of the most recent evidence on the efficacy and safety of old and newly licensed drugs for the treatment of articular and extra-articular RA was performed. In addition, host-related variables potentially driving the therapy choice, such as the infection risk, the cardiovascular risk, the risk of deep vein thrombosis, thromboembolism, pregnancy, and obesity were analyzed. Consequently, several statements for personalized therapy were formulated, thus providing a decisional algorithm useful for proper personalized therapy of RA patients in clinical practice.Several clinical variables related to specific drug and host characteristics may drive the choice toward anti-TNF and non-anti-TNF biologics, or anti-JAKs, thus allowing to personalize the therapy. Consequently, the right therapy for the right patient would ensure a successful therapeutic intervention.

The dual anticytokine and antiviral actions of baricitinib reduce SARS-CoV-2 infectivity in organoids and morbidity in people., Using AI, we identified baricitinib as having antiviral and anticytokine efficacy. We now show a 71% (95% CI 0.15 to 0.58) mortality benefit in 83 patients with moderate-severe SARS-CoV-2 pneumonia with few drug-induced adverse events, including a large elderly cohort (median age, 81 years). An additional 48 cases with mild-moderate pneumonia recovered uneventfully. Using organotypic 3D cultures of primary human liver cells, we demonstrate that interferon-α2 increases ACE2 expression and SARS-CoV-2 infectivity in parenchymal cells by greater than fivefold. RNA-seq reveals gene response signatures associated with platelet activation, fully inhibited by baricitinib. Using viral load quantifications and superresolution microscopy, we found that baricitinib exerts activity rapidly through the inhibition of host proteins (numb-associated kinases), uniquely among antivirals. This reveals mechanistic actions of a Janus kinase-1/2 inhibitor targeting viral entry, replication, and the cytokine storm and is associated with beneficial outcomes including in severely ill elderly patients, data that incentivize further randomized controlled trials.

• Baricitinib, an anti-JAK1/JAK2, reduces cytokine release and SARS-Co-V2 entry. • In a retrospective multicenter study baricitinib reduces COVID-19 mortality rate. • Baricitinib reduces intensive care unit admissions of COVID-19 pneumonia. • Baricitinb reduces SARS-CoV-2 viral burden detected by nasopharyngeal swab. • Baricitinib used for 2 weeks was not associated with serious adverse events.

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

Latent tuberculosis infection (LTBI) accounts for almost a quarter of the world population, and, in 5-10% of the subjects with impaired immune-response against M. tuberculosis growth, it may progress to active tuberculosis (TB). In this review, we focus on the need to propose a screening for LTBI including preventive therapy offer in rheumatic patients undergoing therapy with biological drugs. Areas covered: We report on evidence that biologics are associated with an increased risk of active TB reactivation. This effect seems to be mainly limited to treatment with anti-tumor necrosis factor (TNF) agents, while non-anti-TNF-targeted biologics are not likely associated to any increased risk. We introduce the concept that the patients' coexisting host-related risk factors, such as comorbidities, are crucial to identify those at higher risk to reactivate TB. We report that preventive TB therapy is well tolerated in patients treated with biological drugs. Expert commentary: Availability of non-anti-TNF targeted biologics, that are not associated with an increased risk of TB reactivation, offers a great opportunity to tailor a therapeutic intervention at low/absent TB risk. After proper LTBI screening investigations, preventive TB therapy has been demonstrated to be effective and well-tolerated to reduce the risk of TB reactivation in rheumatic patients requiring biological drugs.

Objective The Italian board for the TAilored BIOlogic therapy (ITABIO) reviewed the most consistent literature to indicate the best strategy for the second-line biologic choice in patients with rheumatoid arthritis (RA), spondyloarthritis (SpA), and psoriatic arthritis (PsA). Methods Systematic review of the literature to identify English-language articles on efficacy of second-line biologic choice in RA, PsA, and ankylosing spondylitis (AS). Data were extracted from available randomized, controlled trials, national biologic registries, national healthcare databases, post-marketing surveys, and open-label observational studies. Results Some previously stated variables, including the patients׳ preference, the indication for anti-tumor necrosis factor (TNF) monotherapy in potential childbearing women, and the intravenous route with dose titration in obese subjects resulted valid for all the three rheumatic conditions. In RA, golimumab as second-line biologic has the highest level of evidence in anti-TNF failure. The switching strategy is preferable for responder patients who experience an adverse event, whereas serious or class-specific side effects should be managed by the choice of a differently targeted drug. Secondary inadequate response to etanercept (ETN) should be treated with a biologic agent other than anti-TNF. After two or more anti-TNF failures, the swapping to a different mode of action is recommended. Among non-anti-TNF targeted biologics, to date rituximab (RTX) and tocilizumab (TCZ) have the strongest evidence of efficacy in the treatment of anti-TNF failures. In PsA and AS patients failing the first anti-TNF, the switch strategy to a second is advisable, taking in account the evidence of adalimumab efficacy in patients with uveitis. The severity of psoriasis, of articular involvement, and the predominance of enthesitis and/or dactylitis may drive the choice toward ustekinumab or secukinumab in PsA, and the latter in AS. Conclusion Taking in account the paucity of controlled trials, second-line biologic therapy may be reasonably optimized in patients with RA, SpA, and PsA.

Introduction: In recent years, biosimilars of reference adalimumab (re-ADA), etanercept (re-ETN) and infliximab (re-IFX) have been licensed. In the absence of specific controlled studies, by the extrapolation principle, biosimilars have been approved for the treatment of psoriatic arthritis (PsA).Areas covered: To assess the efficacy and safety of biosimilars in PsA, the literature, present until 30 June 2019, was reviewed. The literature search was undertaken using the PubMed database to identify English-language papers focusing on biosimilar efficacy in PsA. No specific PsA study was found, and the results were retrieved from trials on different inflammatory rheumatic diseases that were also enrolling patients with PsA. Data on re-IFX biosimilar CT-P13 and re-ETN SB4 were found, but not on re-ADA biosimilars. The results showed a trend toward a reduced efficacy of biosimilars. However, considering the small number of PsA patients, the non-statistically-powered studies, and the inappropriate outcome measures, these results could have occurred by chance.Expert opinion: The few data do not allow to draw definitive conclusions, and emerging results suggest the need of specific trials, and of rigorous registries to evaluate the efficacy and safety of biosimilars in PsA.

Two classes of biologics, anti-tumor necrosis factor (TNF) and non-anti-TNF targeted, are currently available for the treatment of rheumatic diseases.Discussion on the need for LTBI diagnosis in rheumatic patients treated csDMARDs and non-anti-TNFs through a review of the literature. The literature, updated to 15 April 2019, on tuberculosis (TB) reactivation risk in patients exposed to conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) and non-anti-TNF biologics was reviewed.An increased risk of TB reactivation in patients receiving csDMARDs (except sulphasalazine) resulted, while a review of clinical trials, and Periodic Safety Update Reports from pharmaceutical Companies evidenced a very low or absent risk for non-anti-TNF biologics. Hence, a contradiction emerges considering that latent TB infection (LTBI) screening is recommended for non-anti-TNF candidates but not for csDMARDs. Concerning the low TB incidence countries, several actions could be undertaken, including to screen all patients independently on the treatment, to omit the procedure in non-anti-TNF candidates, or to perform the LTBI investigations only in high-risk patients. According to WHO guidelines, LTBI screening in low TB risk countries seems unnecessary, except in high TB risk subjects.

Objective To propose appropriate statements that drive the choice of biologic therapies in patients with rheumatoid arthritis (RA), factoring in their impact on the following issues: anti-drug antibody (ADAb) formation, suspicion and management of infections, lupus-like syndrome (LLS), effects on bone mass and sexual sphere, and relationship between RA and periodontal disease (PD). Methods An overview of existing evidence was undertaken by an expert panel on behalf of the Italian board for the TAilored BIOlogic therapy (ITABIO). Data were extracted from controlled trials, national registries, national health care databases, post-marketing surveys, and, when required by the paucity of controlled studies, from open-label clinical series. Anti-tumor necrosis factor (anti-TNF) and non-anti-TNF-targeted biologics approved for RA were investigated. Results ADAb formation is chiefly associated with anti-TNFs, and it is reduced by combination therapy with methotrexate. To date, ADAb titration is not advisable for clinical practice, and, in case of anti-TNF secondary failure, a non-anti-TNF biologic is indicated. LLS is observed in anti-TNF receivers and, in most cases, resolves without anti-TNF withdrawal. A non-anti-TNF biologic is advisable in patients experiencing LLS. Non-anti-TNFs demonstrated a low or absent infection risk and are preferable in patients with comorbidities. Due to their positive effects on bone mass, anti-TNFs are indicated in women at osteoporosis risk, whereas non-anti-TNF have been poorly investigated. The emerging evidence of the relationship between RA and PD and the effects on anti-TNF efficacy should lead clinicians to consider the periodontal status in RA patients. Anti-TNFs may exert a positive effect on fertility and sexuality, and clinicians should explore these aspects in RA patients. Conclusion The optimization of biologic therapies by taking into proper account the above issues would improve patient outcomes.

Objective.To evaluate the frequency of dactylitis, enthesitis, and anterior uveitis (AU) in spondyloarthritis (SpA) associated with inflammatory bowel disease (IBD-SpA) compared with other SpA, and to assess the role of associated psoriasis in the occurrence of dactylitis and enthesitis.Methods.In a 12-month case-control study, the frequency of dactylitis and enthesitis in 29 patients with ulcerative colitis (UC) and 59 with Crohn disease (CD) who satisfied the Spondyloarthritis international Society criteria for axial or peripheral SpA was compared with 176 controls, including 97 (55.1%) with psoriatic arthritis (PsA), 47 (26.7%) with ankylosing spondylitis (AS), and 32 (18.2%) with nonradiographic axial SpA (nr-axSpA). The occurrence of these features in IBD-SpA with and without psoriasis was also evaluated.Results.Axial, peripheral, or mixed involvement was observed in 46 (52%), 29 (33%), and 13 (15%) patients, respectively; and 14/88 (16%) had psoriasis. Dactylitis was recorded in 4/88 patients (4.5%) with IBD-SpA and in 30 controls (17.4%; p = 0.008), enthesitis in 16 cases (18.1%) and in 78/176 controls (44.3%; p < 0.001), and AU in 3 patients (3.4%) with IBD-SpA and in 26 controls (14.7%; p = 0.01). No significant differences were found between patients with UC-SpA and those with CD-SpA. Dactylitis and enthesitis were significantly more common in patients with IBD-SpA who also had psoriasis compared to those without skin disease (p = 0.009 and 0.003, respectively).Conclusion.Dactylitis, enthesitis, and AU are significantly less frequent in IBD-SpA compared with other types of SpA. Given the frequent association of psoriasis and IBD, overlooking coexistent skin disease may lead to overestimating the frequency of these features.

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

Introduction: Post-operative liver failure (PLF) occurs in approximately 10% of patients undergoing major hepatectomy. Partial portal vein arterialization (PPVA) enhances the regenerative capacity of the resected liver. The aim of this study was to investigate the impact of age on survival after PPVA for the treatment of post-operative liver failure in a rat model. Materials and Methods: 24 rats underwent extended liver resection, that leaded to PLF. 12 rats were divided in 2 groups treated with PPVA: group 1a-young rats (n=6, age 2 months) and group 2a-old rats (n=6, age 30 months). Two control groups of rats of the same age were not treated with PPVA: group 1b-young and group 2b-old. Results: on postoperative day 7, no significant differences were observed among all groups in terms of ALT levels, prothrombin activity and serum creatinine. As for the liver regeneration markers, the level of mitotic index was greater in the groups treated with PPVA compared to the control groups (without significant differences between young and old groups). The 75% (9/12) of the rats treated with PPVA survived up to 7 days, with no significant differences between young (5/6) and elderly rats 66.7% (4/6). Conclusion: PPVA treatment had the same beneficial effect both in young and old rats.

This review evaluates the risk of tuberculosis (TB), adherence with recommendations for TB prevention, and host-related risk in patients with rheumatoid arthritis (RA), psoriatic arthritis, and ankylosing spondylitis receiving infliximab (IFX), adalimumab (ADA), and etanercept (ETN) through an analysis of phase III randomized controlled trials (RCT), postmarketing surveillance, and national registries. Ten (0.21%) TB cases occurred among 4590 patients in 16 RCT of IFX, 9 (0.12%) among 7009 patients in 21 RCT of ADA, and 4 (0.05%) among 7741 patients in 26 RCT of ETN. Overall, 19/23 (83%) TB cases occurred in patients with RA. Data from national registries and postmarketing surveillance showed an increased risk of TB in patients receiving any of the 3 anti-tumor necrosis factor (TNF) drugs, with a 3-4 times higher risk associated with IFX and ADA than with ETN. Deviations from recommended TB prevention procedures were observed in up to 80% of patients, and most registries did not include data on host-related risk factors for TB. TB occurrence was reduced in recent RCT but not in real-life practice. TB risk was lower for ETN than for monoclonal antibody anti-TNF agents. More complete data collection, including host-related TB risk factors, is advisable to avoid biased results.

This review aimed to evaluate the risk of active tuberculosis (TB) occurrence in patients with rheumatic disorders receiving non-anti-tumor necrosis factor (TNF) targeted biologics anakinra (ANK), tocilizumab (TCZ), rituximab (RTX), abatacept (ABA), and recently approved anti-TNF golimumab (GOL), and certolizumab pegol (CTP). In recent findings, no cases of active TB were recorded in patients with rheumatoid arthritis (RA) and other rheumatic conditions treated with anti-CD20+ RTX and anti-CD28 ABA. No patient receiving anti-interleukin 1 (IL-1) ANK developed active TB, and an increased risk was excluded in a Canadian database. In contrast, 8 active TB cases were observed in 21 trials of patients with RA receiving anti-IL-6 TCZ, while no increased TB risk resulted from Japanese postmarketing surveillance. Among GOL-treated and CTP-treated patients, 8 and 10 active TB cases occurred, respectively, while no data are available from registries. However, all but 1 TB case recorded in patients treated with TCZ, GOL, and CTP occurred in TB-endemic countries. No TB risk resulted for ANK, RTX, and ABA, suggesting pretreatment screening procedures for latent TB infection detection are unnecessary. Because all TB cases occurred in countries at high risk for TB, where TB exposure could have occurred during treatment, no definitive conclusions can be drawn for TCZ, GOL, and CTP.

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

Objective A multidisciplinary expert panel, the Italian board for the TAilored BIOlogic therapy (ITABIO), was constituted to formulate evidence-based decisional statements for the first-line tailored biologic therapy in patient with rheumatoid arthritis (RA), spondyloarthritis (SpA), and psoriatic arthritis (PsA). Methods Systematic review of the literature to identify English-language articles on the variables influencing the first-line biologic choice, including the efficacy and safety of the drug, the route of administration, the availability of response predictor biomarkers, the need of monotherapy, the patient socio-economic status, lifestyle, cultural level, personality, fertility and childbearing potential in women, the presence of comorbidities, the host-related risk factors for infection and latent tuberculosis infection (LTBI) reactivation, the cardiovascular (CV) risk, and costs. Results Some variables, including the patients’ preference, the indication for anti-TNF monotherapy in potential childbearing women, and the intravenous route with dose titration in obese subjects resulted valid for all the three rheumatic conditions. Further, evidence of a better cost-effectiveness profile for etanercept (ETN) and biosimilar infliximab (IFX) in RA was found. Any biologic may be employed in absence of choice driving factors in RA. Otherwise, a high infection risk or LTBI positivity drive the choice toward abatacept (ABA), tocilizumab (TCZ), or ETN. TCZ should be the first choice if monotherapy is required. High rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPA) titers should drive the choice toward TCZ or ABA, while in patients at high CVD risk anti-TNF choice, with preference for ETN, seems appropriate. Presence of anterior uveitis or inflammatory bowel disease drives the choice to monoclonal antibody anti-TNFs (MoAb anti-TNFs). In PsA, ustekinumab (UTK), and to a lesser extent ETN, represents the first choice in patients at high infection and TB risk. Anti-TNFs or UTK choice is guided by skin or articular disease severity, enthesitis, and dactylitis, whereas ETN should be preferred if metabolic syndrome or high CV risk complicate PsA. Conclusion Taking in account of multiple choice driving variables, first-line biologic therapy may be optimized in patients with RA, SpA, and PsA.

Objective The occurrence of iridocyclitis (IC) in early psoriatic arthritis (PsA) has been rarely assessed. The primary end-point of this study was to evaluate the frequency of IC at onset in patients with early PsA. Methods We evaluated the frequency of IC in a clinical series of consecutive, new outpatients with early PsA observed between January 2000 and December 2009. All patients met the Classification Criteria for Psoriatic Arthritis (CASPAR) criteria for PsA and had a disease duration ≤12 months. The following clinical patterns were considered: peripheral PsA (oligoarthritis ≤4 and polyarthritis ≥5 involved joints), axial PsA and mixed. IC diagnosis was made by the ophthalmologist. Follow-up visits were scheduled at baseline and every 4 months with interval shortening in the case of urgent clinical problems. Results Two hundred and forty-two patients, 137 (57%) women and 105 (43%) men (mean age 50.33 ± 11.7 years; mean symptom duration 9.38 ± 3.1 months) were studied. One hundred and thirty-two (51%) patients had peripheral PsA, 41 (17%) axial and 69 (28%) mixed. Twenty-six episodes of IC were recorded at diagnosis in 22 (9%) patients, 17 (77.3%) female and five (22.7%) male; 11 (50%) patients had peripheral PsA, two (9.1%) axial, and nine (40.9%) mixed; 5/22 (22.7%) patients were B27-positive. IC recurred in 2/22 (9%) patients over the follow-up period. Mean follow-up duration was 51 ± 23.2 months. Dactylitis was significantly more frequent in patients with IC compared to those without this feature (P = 0.032). Conclusion IC occurred in 9% of 242 patients with early PsA with no association with the clinical pattern and B27 positivity. This frequency is higher than previously reported.

Fabrizio Cantini1, Laura Niccoli1, Carlotta Nannini1, Olga Kaloudi1, Emanuele Cassarà1, Massimo Susini2, Ivo Lenzetti21Second Division of Internal Medicine, Rheumatology Unit, 2Division of Ophthalmology, Prato Hospital, Prato, ItalyPurpose: To evaluate the long-term efficacy of infliximab in patients with refractory Behçet’s disease (BD)-associated and idiopathic posterior uveitis (PU).Methods: Single center, prospective, 6-year duration, follow-up study on 50 consecutive patients (20 [40%] males and 30 [60%] females with a mean age of 37.5 ± 12.3 years) with refractory BD-associated PU (36 patients) and idiopathic PU (14 patients) who had failed at least one immunosuppressive drug. At baseline, patients received prednisone 1 mg/kg/day with rapid tapering and infliximab infusions (5 mg/kg) at weeks 0, 2, 6, and every 8 weeks thereafter. Nonresponders after the third infusion withdrew from the study. Primary outcome measures were visual acuity (VA) value improvement compared to baseline. Secondary outcome measures were proportion of patients with VA improvement from baseline; proportion of patients achieving disease remission; number of PU flare-ups; and incidence of adverse events.Results: At the final follow-up, mean right and left eye VA respectively increased from 0.57 ± 0.31 at baseline to 0.68 ± 0.33 (P = 0.048) and from 0.67 ± 0.28 to 0.76 ± 0.27 (P = 0.047). None of the patients had VA worsening and new onset ocular complications. A complete response of PU was recorded in 34/50 (68%) patients and partial response in 11/50 (22%). Five patients were nonresponders and withdrew from the study after the third infusion. A significant reduction of ocular attacks and of the proportion of patients with cystoid macular edema was observed. No differences in infliximab efficacy was recorded between patients with BD-associated and idiopathic PU. No serious adverse events occurred. The mean follow-up duration was 36.8 months.Conclusion: Long-term infliximab therapy was equally effective and safe with a significant VA gain in refractory BD-associated and idiopathic PU.Keywords: Behçet’s disease, idiopathic posterior uveitis, infliximab, posterior uveitis, visual acuity

Objective: Primary: to evaluate the frequency of anemia of inflammation (AOI) in a clinical series of patients with ankylosing spondylitis (AS) requiring anti-TNF (tumor necrosis factor) agents. Secondary: to examine anti-TNF therapy-induced changes in AOI. Method: Prospective, follow-up, 6-month study of all consecutive, new patients with AS requiring anti-TNFα drugs observed between January 2004 and December 2008. AOI was defined according to WHO criteria. Primary outcome measure: the proportion of patients showing AOI at baseline. Secondary outcome measures: the proportion of patients achieving resolution of AOI at the 6-month visit; the proportion of patients achieving any improvement in haemoglobin (Hb); the proportion of patients with any improvement in blood results. Results: One hundred and six patients (42 women and 64 men; mean age: 46 years) with AS were evaluated. Sixteen of these (15%) presented with AOI at baseline. After 6 months therapy 13 patients (81%) resolved AOI while two presented an Hb level reduction. After 6 months therapy we did not find a significant statistical improvement in red blood cell numbers (P = 0.85) and transferrin (P = 0.08) levels. Hb, mean corpuscular volume (MCV), iron, ferritin, C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) improved reaching statistical significance (P = 0.0002, 0.0001, 0.001, 0.014; 0.007, 0.004, respectively). Conclusion: We found 15% frequency of AOI among a selected series of patients with AS. After 6 months of anti-TNFα therapy AOI resolved in the majority of patients with significant improvement of Hb, MCV, CRP and ESR levels.

Psoriatic arthritis is an inflammatory rheumatic disorder of unknown etiology occurring in patients with psoriasis. The Classification Criteria for Psoriatic Arthritis study group has recently developed a validated set of classification criteria for psoriatic arthritis with a sensitivity of 91.4% and a specificity of 98.7%. Three main clinical patterns have been identified: oligoarticular (≤ 4 involved joints) or polyarticular (≥ 5 involved joints) peripheral disease and axial disease with or without associated peripheral arthritis. In this context distal interphalangeal arthritis and arthritis mutilans may occur. According to other reports, also in our centre, asymmetric oligoarthritis is the most frequent pattern at onset. Axial disease has been estimated between 5% and 36% of patients. It is characterized by an irregular involvement of the axial skeleton with a predilection for the cervical spine. Recurrent episodes of enthesitis and dactylitis represent a hallmark of psoriatic arthritis. In around 20% of cases distal extremity swelling with pitting edema of the hands or feet is observed. Unilateral acute iridocyclitis, usually recurrent in alternate fashion, is the most frequent extra-articular manifestation, and accelerated atherosclerosis is the prominent comorbidity. The clinical course of peripheral and axial psoriatic arthritis is usually less severe than rheumatoid arthritis and ankylosing spondylitis, respectively. Local corticosteroid injections and non-steroidal anti-inflammatory drugs are recommended in milder forms. Sulphasalazine and methotrexate are effective in peripheral psoriatic arthritis. Recent studies have provided evidence on the efficacy of anti-tumor necrosis factor-α drugs to control symptoms and to slow or arrest radiological disease progression.

Objective: To evaluate the inflammatory involvement of cervical interspinous bursae in patients with polymyalgia rheumatica (PMR) using magnetic resonance imaging (MRI). Methods: Twelve consecutive, untreated new patients with PMR were investigated. Five patients with fibromyalgia, 2 patients with cervical osteoarthritis and 6 patients with spondyloarthritis with neck pain served as controls. MRI of the cervical spine was performed in all 12 PMR case-patients and in 13 control-patients. Two of the 4 PMR patients with pelvic girdle pain also had MRI of the lumbar spine. Results: MRI evidence of interspinous cervical bursitis was found in all patients with PMR, and in 3 patients with fibromyalgia, in 2 with psoriatic spondylitis and 1 with cervical osteoarthritis. A moderate to marked (grade >2 on a semiquantitative 0-3 scale) cervical bursitis occurred significantly more frequently in patients with PMR than in control-patients (83.3% compared with 30.7%, p=0.015). In all patients and controls with cervical bursitis the involvement was found at the C5-C7 cervical interspaces. MRI of the lumbar spine showed lumbar interspinous bursitis at the L3-L5 lumbar interspaces in the 2 patients with PMR and pelvic girdle pain examined. Conclusions: Cervical interspinous bursitis is a likely basis for discomfort in the neck of patients with PMR. The prominent inflammatory involvement of cervical bursae supports the hypothesis that PMR is a disorder of prominent involvement of extra-articular synovial structures.

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

Objective: To evaluate the correlation between antinucleosome antibodies and disease activity in patients with systemic lupus erythematosus (SLE).Methods: We evaluated antinucleosome antibodies (by ELISA) in 48 SLE patients. They were divided in 2 groups: positive (Group A, nr=18) and negative (Group B, nr=30). The groups were evaluated for antinucleosome antibodies and for clinical, humoral parameters (hemoglobin, blood cell count, urinanalysis, ESR, ANA, anti‐dsDNA, anticardiolipin antibodies, LAC), and ECLAM.Results: C3,C4, and hemoglobin were lower in Group A than (vs) group B (C3: 0.61±0.16 g/L vs 0.88±0.08 g/L, p

Objective To establish by means of fast spin echo (FSE)–T2-weighted sequences with fat saturation if enthesitis of the flexor digitorum superficialis and profundus tendons is the primary lesion in spondylarthritis (SpA) finger dactylitis. Methods Eleven dactylitic fingers and their corresponding normal, contralateral fingers, belonging to 6 patients who met the Amor criteria for SpA, were studied by FSE–T2-weighted sequences with fat saturation. Results All dactylitic fingers showed moderate or severe fluid collection in the flexor tendon synovial sheaths. Involvement of the joint cavity was simultaneously present in at least one joint in 3 (27.3%) of the 11 fingers. A mild to moderate peritendinous soft tissue edema was observed in 5 (45.5%) of the 11 affected fingers. In no dactylitic finger was bone edema observed near the insertions of the flexor digitorum superficialis or profundus tendons or in other sites of the phalanges. No lesions were observed in the 11 contralateral, clinically normal fingers. Conclusion In SpA dactylitis there is no evidence of enthesitis of the flexor digitorum tendons and joint capsules.

To investigate the inflammatory involvement of shoulder articular and extraarticular structures in polymyalgia rheumatica (PMR) patients with a normal erythrocyte sedimentation rate (ESR) at diagnosis.This was a case-control study. All consecutive, untreated new outpatients diagnosed as having PMR with a normal ESR (40 mm/hour) during a 6-month period were included in the study (case patients). Controls were 12 consecutive, untreated PMR outpatients with an ESR of40 mm/hour who were observed after the case patients. Before starting corticosteroid therapy, all case patients and controls underwent bilateral shoulder ultrasonography (US) and magnetic resonance imaging (MRI). US and MRI scans were evaluated independently by two radiologists who were blinded to the reciprocal results.Six case patients (4 men and 2 women) and 12 controls (4 men and 8 women) were studied. Both US and MRI demonstrated bilateral subacromial/subdeltoid bursitis in all 6 case patients and in 11 of the 12 (92%) controls (P not significant [NS]). One control had unilateral bursitis. Glenohumeral joint synovitis was found in 4 of 6 case patients (67%) by MRI and in 3 of 6 case patients (50%) by US (P NS), as well as in 8 of 12 controls (67%) by MRI and in 7 of 12 controls (58%) by US (P NS). Both MRI and US detected biceps tenosynovitis in 5 of 6 case patients (83%) and in 8 of 12 controls (67%) (P NS). The severity of bursitis did not differ significantly between the groups. US was as effective as MRI in detecting inflammatory changes of the shoulder.MRI and US studies showed that PMR patients with normal or high ESRs have similar inflammatory shoulder lesions. Moreover, bilateral subacromial/subdeltoid bursitis represents the imaging hallmark in PMR patients with a high or normal ESR. MRI or US of the shoulder may facilitate the proper diagnosis in patients with the typical proximal symptoms of PMR who also have normal ESRs.

Objective To determine the frequency and the characteristics of distal musculoskeletal manifestations in polymyalgia rheumatica (PMR). Methods Prospective followup study of 177 consecutive patients meeting clinical criteria for PMR, diagnosed over a 5-year period in 2 rheumatology secondary referral centers in Italy. Results Seventy-nine of the 177 patients (45%) had distal musculoskeletal manifestations. Peripheral arthritis occurred in 45 patients (25%), carpal tunnel syndrome in 24 (14%), distal extremity swelling with pitting edema in 21 (12%), and distal tenosynovitis in 5 (3%). These manifestations were usually associated with PMR proximal symptoms (69%); however, 31% of the episodes represented isolated relapse/recurrence at distal sites. Distal symptoms responded promptly to corticosteroids. No evidence of joint deformities, erosions, or development of rheumatoid arthritis was observed during the followup. The group of patients with peripheral arthritis included a higher proportion of females, had a longer duration of therapy, and had more relapses/recurrences. Patients who had distal extremity swelling with pitting edema had a higher age at disease onset, a shorter duration of therapy, and lower initial and cumulative prednisone doses. Conclusion Inflammatory involvement of distal articular and/or tenosynovial structures occurs in approximately half of the cases of PMR. Peripheral arthritis is associated with more severe disease, while distal extremity swelling with pitting edema appears to identify a more benign disease subset.

Objective: To evaluate the efficacy and toxicity of cyclosporin A (CsA) in the treatment of patients with psoriatic arthritis (PsA). Methods: We reviewed the literature dealing with CsA treatment of PsA. Results: In the 1980s, some studies evaluating CsA in severe cases of psoriasisdocumented an improvement in the associated arthritis. Subsequently, open prospective studies included patients with active peripheral arthritis. Using initial CsA doses of 3 to 6 mg/kg/day, improvement in the clinical parameters was noted. A controlled trial showed that CsA and methotrexate (MTX) are equally effective treatment for PsA. CsA and MTX combination was effective in PsA patients resistant to previous second-line therapy. No studies have evaluated the efficacy of CsA on axial disease and on the progression of radiological damage. The most important side effect was nephrotoxicity. However, of 170 CsA-treated patients in 16 studies, only 10 (6%) discontinued the drug because of renal side effects. Conclusions: CsA seems to be an effective and safe therapy for PsA. However, controlled studies on large number of patients are necessary.

The cases of 2 women with pyoderma gangrenosum (PG) and undifferentiated seronegative spondylarthropathy (SpA) are described. These 2 cases, together with the recently reported case of PG and B27-positive psoriatic spondylarthropathy, suggest that PG may also occur in association with forms of seronegative SpA that are different from primary ankylosing spondylitis (AS) and AS associated with inflammatory bowel disease.

To evaluate the effects of the short-term, high-dose sodium heparin therapy on biochemical markers of bone metabolism, we studied 20 patients (11 males and 9 females) with pulmonary embolism, treated with sodium heparin (daily dose range: 40,000-45,000 I.U. by continuous i.v. infusion). Heparin therapy lasted 5-7 days, after which patients received warfarin over 12 months. Eleven patients (6 males and 5 females) with ischaemic stroke, treated with i.v. glycerol and pentoxifilline, were used as controls. Before and after therapy serum and urinary markers of bone metabolism were evaluated; in 12 heparin-treated pts., the parameters were also evaluated 4 months after discontinuation of warfarin therapy. After heparin therapy a significant reduction vs. basal value was observed in levels of serum osteocalcin (ng/ml;mean + SEM): 3.320.19 vs. 2.05 + 0.21; p0.001. In the 12 patients evaluated 4 months after discontinuation of warfarin therapy, serum osteocalcin levels returned to basal value: 3.41 + 0.12 ng/ml (p:n.s.). No significant changes of the examined parameters were observed in controls. In conclusion, our data seem to indicate an effect of i.v. short-term heparin therapy on bone metabolism. This effect seems to be characterized by an inhibition of osteoblast function as suggested by the reduction of serum osteocalcin levels.

Background Musculoskeletal involvement, preferentially affecting hands and feet, represents a frequent feature and may lead to disability in patients with systemic sclerosis (SSc). The most common manifestations are arthralgia, stiffness, synovitis, and tenosynovitis. In a large multicentre study, synovitis, tendon friction rubs, and joint contractures were found in 16%, 11%, and 31% of 7286 SSc patients assessed by clinical examination 1 . However, several ultrasound (US) studies revealed a higher frequency of hand joint involvement 2 . Objectives To investigate the frequency and severity of hand joint involvement in a cohort of SSc patients evaluated by US, and to compare the results of US synovitis detection with those of physical examination. Methods Over a 6-month period, all consecutive (new and old diagnosis) SSc patients (ACR/EULAR 2013 criteria) currently followed in our center underwent clinical and US hand examination. One rheumatologist expert in musculoskeletal US performed all examinations by using Esaote Technos MPX, MyLab 40, employing high frequency (12–18 MHz) transducers. Power Doppler (PD) parameters were adjusted (range of pulse repetition frequency 400–800 Hz; frequency 7–11.1 MHz). Patients were scheduled to be examined at the same hour of the day in the same room with an ambient temperature of 21°C. Hand and wrist joints were evaluated for synovitis, tenosynovitis, calcinosis, acro-osteolysis and distal vascularization. An independent rheumatologist made the clinical examination and US examiner was blind to clinical findings. US assessment of synovitis was scored according to the OMERACT–EULAR PD composite semiquantitative scale (0–3). Results 89 patients, 79F/10M, mean age 61.11±15.1, median disease duration 160 months (min: 2,max: 492), 83 (93%) with limited SSc and 6 (7%) with diffuse SSc were recruited. Synovitis was detected in 15 (16.8%) and in 35 (40.2%) of the cases by clinical examination and US, respectively (p=0.019). PD revealed grade 1 synovitis in 19/35 (54.3%) patients, grade 2 in 14 (40%) and grade 3 in 2 (5.7%). Tenosynovitis, calcinosis and acro-osteolysis were found at US 19 (21.3%), 14 (15.7%), acro-osteolysis in 11 (12.3%) and 8 (9%), respectively. Distal vascularization was detected in 60 patients (67%). Conclusions Confirming previous studies, our results show that hand synovitis in SSc may be underestimated by clinical examination only, while US examination provides an accurate assessment of the frequency and the degree of severity of synovial inflammation. However, synovitis in our cohort of SSc patients resulted mild in the majority of the cases. References Avouac J, et al. J Rheumatol. 2010;37:1488–501.2.Cuomo G, et al. Rheumatology (Oxford) 2009;48:1414–1417. Acknowledgement None Disclosure of Interest None declared

Background Dactylitis, is observed in approximate 30% of patients spodnyloarthritis (SpA),with the highest frequency in psoriatic arthritis (PsA).SpA features complicate inflammatory bowel diseases (IBD) in at least one third of the cases.The frequency of dactylitis in IBD-SpA has been assessed in a few open studies with conflicting results1,2. Objectives Primary end point: To compare the frequency of dactylitis in a clinical series of patients with IBD-associated SpA (IBD-SpA) compared with other types of SpA. Secondary end point: to evaluate the frequency of articular and extra-articular manifestations of IBD-associated SpA compared to controls. Methods 24-month case-control study. Case patients: all consecutive patients meeting the ASAS criteria for both axial and peripheral SpA,and with a diagnosis of Crohn9s disease (CD) or ulcerative colitis (UC) certified by the gastroenterologist. Controls: the 2 consecutive patients with other SpA (ASAS criteria) observed after the case patient during the same time interval. Dactylitis diagnosis was accepted if observed at visit or if certified in the past by a rheumatologist working in our center.Patients were followed by the same rheumatologist,and follow-up visits were scheduled at baseline and every 4 months.All clinical and laboratory data were recorded in a computed patients9chart. The date of the last visit constituted the end of the follow-up. Results Case patients:88 IBD-SpA patients, 29 UC and 59 CD, 42 F/46M, mean age 47.66±15.09 ys, 10 (11.3%) B27+.Mean IBD duration was 60.05±54.66 months. Controls: 176 SpA patients, 98 PsA, 46 AS, and 32 non-radiographic axial SpA (nrx-AxSpA); 89F/87M, mean age 46.35±24.88 ys. 70 (40.7%) B27+, mean disease duration of 43.21±28.34 months. In IBD-SpA axial involvement was observed in 46 (52%) patients, peripheral in 29 (33%) and mixed in 13 (15%). Peripheral SpA was oligoarticular (≤4 joints involvement) in 26/29 (90%) patients and polyarticular in 3 (10%). Psoriasis (Pso) was associated in 14/88 (16%) of the cases. Dactylitis was recorded in 4 (4.5%) of IBD-SpA patients and in 30 (17.4%) of controls with a significant statistical difference (p=0.018). Dactylitis was recorded in only 2/74 (2.7%) IBD-SpA patients without Pso (p vs controls=0.010).Also enthesitis prevalence was significantly lower in IBD-SpA occurring in 16/88 (18.1%) patients and in 78/176 (44.3%) controls (p=0.004). Enthesitis frequency was significantly higher in 14 IBD-SpA patients associating Pso (28.5%) compared with the remaining 74 cases (16.2%) (p=0.012). Dactylitis occurred in 2/29 (6.9%) and in 2/59 (3.38%) patients with UC and CD, respectively. Anterior uveitis was recorded in 3 (3.4%) IBD-SpA patients and in 26 (14.7%) controls (p=0.02). Conclusions Dactylitis and enthesitis were significantly lower in IBD-SpA patients compared to other SpA. As reported3, Pso was frequent in our cohort of IBD-SpA,and its coexistency significantly increased the frequency of enthesitis and to a lesser extent of dactylitis.Anterior uveitis was significantly less frequent in IBD-SpA compared to controls. References Salvarani C, et al. Scand J Rheumatol 2001; Alamino RP, et al. J Rheumatol.2011; Li W-Q, et al. Ann Rheum Dis 2013. Disclosure of Interest None declared

Objective To compare two staining methods to assess sperm morphology: Diff-Quik (DQ), which is the fastest of the recommended techniques, and Testsimplets (TS), a technique that uses prestained slides and is quite popular in in vitro fertilization (IVF) centers. Design Prospective study. Setting Patients at the Sterility Center of the Obstetrics and Gynecology Unit of the Hospital of S.S. Cosma and Damiano (Azienda USL 3 of Pistoia, Italy). Patient(s) 104 randomly enrolled male patients evaluated by the seminology laboratory. Intervention(s) None. Main Outcome Measure(s) Statistical comparison of sperm morphology results obtained after staining of semen samples both with DQ and TS. Result(s) Our data show that TS gives a statistically significantly lower number of normal forms than DQ (median: 6% [range: 0–29%] vs. 12% [range: 0–40%], respectively) as well as an overestimation of sperm head defects (median: 92.0% [range: 67%–100%] vs. 82.3% [range: 55%–100%], respectively). Conclusion(s) The two staining methods should not be considered equivalent. Specifically, the lower reference limit established by the World Health Organization is not appropriate when sperm morphology is assessed by TS. The routine application of TS in the evaluation of sperm morphology is therefore not recommended because it leads to an overestimation of patients with sperm morphology values below the lower reference limit (4%), thus potentially influencing clinical decisions.

Fabrizio Cantini, Laura Niccoli, Emanuele Cassarà, Olga Kaloudi, Carlotta NanniniDivision of Rheumatology, Misericordia e Dolce Hospital of Prato, Prato,ItalyPurpose: The primary purpose of this study was to evaluate the proportion of psoriatic arthritis (PsA) patients maintaining clinical remission after adalimumab (ADA) dose reduction compared with patients with rheumatoid arthritis. Secondary purposes include evaluating the proportion of PsA patients who achieve remission, the duration of remission after ADA dose reduction, time to relapse, psoriasis course, and the frequency of adverse events at the end of follow-up.Methods: This was a single-center, prospective, follow-up, case-control study of 76 consecutive patients (35 females, 41 males; mean age 46 ± 10.2 years) who met the classification criteria for psoriatic arthritis and required anti-tumor necrosis factor therapy according to Group for Research and Assessment of Psoriasis and Psoriatic Arthritis recommendations. The 76 patients were compared with 55 patients (40 females, 15 males; mean age 50 ± 11.6 years) who satisfied the American College of Rheumatology criteria for rheumatoid arthritis and received the same treatment. Case patients and controls were recruited from January 2008 to December 2010. At baseline, PsA patients and controls received 40 mg of ADA every other week, usually with methotrexate (10 to 20 mg/weekly). In the presence of clinical remission, ADA dose was reduced to 40 mg every 4 weeks in both groups.Results: Fifty-three of the 76 (69.7%) PsA patients and 17 of the 55 (30.9%) rheumatoid arthritis (P < 0.019) controls achieved remission after a mean time of 5.1 ± 1.2 and 6.3 ± 1.6 months, respectively (P = nonsignificant). After halving the dose of ADA, 47 of the 53 (88.6%) PsA patients and three of the 17 (17.6%) controls maintained remission (P = 0.016) over a mean follow-up period of 28.9 ± 8.4 and 24.2 ± 6.4 months, respectively. No significant changes in Psoriatic Arthritis Severity Index scores were observed. The mean time to relapse was 8.3 ± 3.4 months in six case patients and 7.2 ± 4.2 in 14 controls (P = not significant). No serious adverse events occurred in either group.Conclusion: Clinical remission is possible in a high percentage of patients with early PsA receiving ADA. Such remission is maintained in a high proportion of subjects after ADA dose halving, with relevant advantages in terms of patient compliance, drug-exposure risk, and economic burden.Keywords: psoriatic arthritis, anti-TNF, adalimumab, remission, dose reduction

Tumor necrosis factor-α (TNF-α) plays a central role in the pathogenesis of psoriasis and psoriatic arthritis (PsA). Recently, 2 expert committees provided evidence-based recommendations for the treatment of PsA. Anti-TNF-α drugs are indicated in all forms of PsA resistant to traditional therapeutic approaches. Anti-TNF-α infliximab (IFX) is an immunoglobulin G-1 antibody that binds to soluble and cell membrane-bound TNF-α with its inactivation. Confirming previous open-label studies, 2 randomized, placebo-controlled clinical trials, IMPACT and IMPACT2, have provided evidence of the efficacy and safety of IFX in the treatment of PsA as evaluated by American College of Rheumatology (ACR)20, ACR50, and ACR70 response rates. At Week 16, a significant proportion of 51 IFX-treated patients achieved ACR20, ACR50, and ACR70 responses compared to the 51 patients of the placebo arm in the IMPACT trial. In the IMPACT2 study, 58% of the IFX-treated patients and 11% of placebo patients achieved an ACR20 response (p < 0.001), and 41% and 27% of patients in the IFX group were ACR50 and ACR70 responders, compared with 4% and 2% of placebo patients, respectively. Of note, a significant inhibition of radiographic disease progression was observed in the IFX-treated group. In both trials, psoriasis improvement was recorded in more than 80% of patients receiving IFX, with a significant difference compared to placebo group. IFX was well tolerated, with no difference compared to placebo in terms of adverse events. The extension phase of these studies showed the sustained efficacy and safety of the drug.

Primary: to evaluate the frequency of anemia of inflammation (AOI) in a clinical series of patients with ankylosing spondylitis (AS) requiring anti-TNF (tumor necrosis factor) agents. Secondary: to examine anti-TNF therapy-induced changes in AOI.Prospective, follow-up, 6-month study of all consecutive, new patients with AS requiring anti-TNFα drugs observed between January 2004 and December 2008. AOI was defined according to WHO criteria.the proportion of patients showing AOI at baseline.the proportion of patients achieving resolution of AOI at the 6-month visit; the proportion of patients achieving any improvement in haemoglobin (Hb); the proportion of patients with any improvement in blood results.One hundred and six patients (42 women and 64 men; mean age: 46 years) with AS were evaluated. Sixteen of these (15%) presented with AOI at baseline. After 6 months therapy 13 patients (81%) resolved AOI while two presented an Hb level reduction. After 6 months therapy we did not find a significant statistical improvement in red blood cell numbers (P = 0.85) and transferrin (P = 0.08) levels. Hb, mean corpuscular volume (MCV), iron, ferritin, C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) improved reaching statistical significance (P = 0.0002, 0.0001, 0.001, 0.014; 0.007, 0.004, respectively).We found 15% frequency of AOI among a selected series of patients with AS. After 6 months of anti-TNFα therapy AOI resolved in the majority of patients with significant improvement of Hb, MCV, CRP and ESR levels.

Psoriatic arthritis is an inflammatory rheumatic disorder of unknown etiology occurring in patients with psoriasis. The Classification Criteria for Psoriatic Arthritis study group has recently developed a validated set of classification criteria for psoriatic arthritis with a sensitivity of 91.4% and a specificity of 98.7%. Three main clinical patterns have been identified: oligoarticular (≤ 4 involved joints) or polyarticular (≥ 5 involved joints) peripheral disease and axial disease with or without associated peripheral arthritis. In this context distal interphalangeal arthritis and arthritis mutilans may occur. According to other reports, also in our centre, asymmetric oligoarthritis is the most frequent pattern at onset. Axial disease has been estimated between 5% and 36% of patients. It is characterized by an irregular involvement of the axial skeleton with a predilection for the cervical spine. Recurrent episodes of enthesitis and dactylitis represent a hallmark of psoriatic arthritis. In around 20% of cases distal extremity swelling with pitting edema of the hands or feet is observed. Unilateral acute iridocyclitis, usually recurrent in alternate fashion, is the most frequent extra-articular manifestation, and accelerated atherosclerosis is the prominent comorbidity. The clinical course of peripheral and axial psoriatic arthritis is usually less severe than rheumatoid arthritis and ankylosing spondylitis, respectively. Local corticosteroid injections and non-steroidal anti-inflammatory drugs are recommended in milder forms. Sulphasalazine and methotrexate are effective in peripheral psoriatic arthritis. Recent studies have provided evidence on the efficacy of anti-tumor necrosis factor-α drugs to control symptoms and to slow or arrest radiological disease progression.

This article outlines our case-control, prospective, 6-year followup study to evaluate the frequency of clinical remission and duration of remission episodes in patients with peripheral psoriatic arthritis (PsA). All case patients were consecutive new outpatients with peripheral PsA requiring second-line drugs. Controls were consecutive new outpatients with rheumatoid arthritis (RA). Modified American College of Rheumatology criteria for RA were used to assess the remission in patients with PsA. One or more episodes of remission occurred in 57/236 (24.1%) PsA patients and in 20/268 (7.5%) controls (p0.001). No significant difference was recorded for duration of remissions between the group receiving traditional disease modifying antirheumatic drug (DMARD) and the anti-tumor necrosis factor (TNF) group: 11 +/- 7.2 and 13.3 +/- 8.1 months, respectively (p = NS). The duration of remission after interruption of therapy was 12 +/- 2.4 months for the PsA group and 3 +/- 1.5 months for patients with RA (p0.001). No predictor of remission at diagnosis could be determined by multivariate analysis. Based on our findings, remission is possible in up to 24% of patients with peripheral PsA. It is significantly more frequent, but not longer, in patients receiving anti-TNF drugs compared to those treated with traditional DMARD.

To evaluate the frequency and duration of clinical remission in patients with PsA.All consecutive new outpatients with peripheral PsA requiring second-line drugs and RA observed between January 2000 and December 2005 were included in a prospective, case-control study. Primary end point was to assess the frequency of remission in peripheral PsA compared with RA. Secondary end points were to compare the duration of clinical remission during treatment and after therapy interruption, ACR 20, 50, 70 response rates and to detect any remission predictor at diagnosis. Treatment regimen was standardized in both groups. From January 2003 to December 2005, therapy was suspended in PsA patients and controls if achieving remission.One or more episodes of remission occurred in 57/236 (24.1%) PsA patients and in 20/268 (7.5%) controls (P0.001). The mean duration of remission was of 13 +/- 9.4 months in PsA patients and 4 +/- 3.7 in controls (P0.001). Remission episodes were more frequent in PsA patients treated with anti-TNF compared with those receiving traditional DMARDs (P0.001), with no differences regarding the duration. After therapy interruption, the remission duration was 12 +/- 2.4 months in PsA and 3 +/- 1.5 in RA (P0.001). No remission predictor at diagnosis resulted by multivariate analysis.Remission is possible in up to 24% of patients with peripheral PsA. It is significantly more frequent, but not longer, in patients receiving anti-TNF drugs compared with those treated with traditional DMARDs. Patients remain in remission for a long period after therapy interruption, thus suggesting an intermittent therapeutic strategy.

Objective: To describe isolated knee monoarthritis as a paraneoplastic syndrome heralding non-small cell lung cancer (NSCLC), and to discuss its clinical characteristics. Methods: We reviewed the clinical records of all consecutive, new outpatients with isolated knee monoarthritis observed from January 2000 to December 2005. A systematic review of Medline and Cochrane Library databases was performed to identify English-language articles related to rheumatologic paraneoplastic syndromes associated with NSCLC. Results: Over 6 years, we observed 6654 new outpatients with different rheumatic disorders. Of these, 296 (4.4%) presented with isolated monoarthritis of the knee. In 5 out of 296 (1.7%) patients this feature represented the initial manifestation of NSCLC. All 5 patients were middle aged males, with a long history of heavy cigarette smoking, who had a nonerosive, isolated knee monoarthritis, with mild articular fluid collection of non inflammatory type. NSCLC was resectable in all patients, and knee monoarthritis remitted with no relapse confirming its paraneoplastic nature. All 5 patients are in good condition after a median follow up of 41 months. The literature review revealed that paraneoplastic knee monoarthritis has not been previously reported. Conclusion: Knee monoarthritis may represent in some cases a paraneoplastic syndrome heralding NSCLC in an early stage.

We aimed to establish by using fast spin echo (FSE)-T2-weighted sequences with fat saturation if flexor tendon enthesitis is the primary lesion in spondyloarthritis (SpA) toe dactylitis. Consecutive patients showing toe dactylitis and meeting Amor criteria for the classification of SpA were enrolled. Dactylitic toes and their corresponding normal contralateral digits were studied by FSE-T2-weighted sequences with fat saturation. Twelve dactylitic toes belonging to ten SpA patients were studied. All dactylitic toes showed mild-to-moderate fluid collection in the synovial sheaths of flexor digitorum brevis and longus. Involvement of joint cavity was simultaneously seen in at least one joint of eight (66.6%) out of the 12 toes. A mild-to-severe peritendinous soft tissue edema was observed in all but one of the affected toes. In no dactylitic toe was bone edema observed either near the insertions of the flexor digitorum brevis and longus tendons or in other sites of the phalanges. No lesions were observed in the 12 contralateral clinically normal toes. In SpA toe dactylitis there is no evidence of enthesitis of the flexor digitorum brevis and longus tendons and joint capsules.

Objectives. To evaluate the long-term efficacy and safety of infliximab in patients with Behcet's disease (BD) and refractory bilateral posterior uveitis, and to assess the proportion of relapse-free subjects through months 12 and 24. Methods. Open-label, multicentre, 24-month, prospective, follow up study on 12 consecutive patients with BD and refractory posterior uveitis who had failed at least one immunosuppressive drug. At baseline patients received prednisolone 1 mg/Kg/day with rapid tapering and nine infliximab infusions (5 mg/kg) over a 12-month period. Non-responders after the third infusion withdrew from the study. Patients were evaluated for ocular inflammation degree, visual acuity (VA), number of ocular attacks and incidence of adverse events (AEs). Results. At 12-month visit, 9/12 (75%) patients achieved a complete remission with no relapse during the treatment period. All had a dramatic improvement of ocular inflammation after the first infusion, six were in complete remission after three infusions, and three after four. All these patients suspended corticosteroids at week 22. At 24-month visit, seven out of nine (78%) were still in remission. Mean VA improved from 0.2 � 0.6 to 0.5 � 0.2 (P < 0.001), and ocular attacks dropped from 40 in the year before therapy to 5 after infliximab cessation (P < 0.001). One patient had a partial remission with two relapses during treatment, and 2/12 (17%) patients showed no improvement. Infliximab was well tolerated with no serious AEs. Conclusions. Infliximab is rapidly effective and safe in a high proportion BD patients with refractory posterior uveitis, and may be helpful to prevent recurrences.