Effectiveness and safety of filgotinib in rheumatoid arthritis: a real-life multicentre experience.

OBJECTIVES: We investigated the effectiveness and safety of filgotinib in a real-life multicentre cohort of rheumatoid arthritis (RA) patients. METHODS: RA patients were evaluated at baseline and after 12 and 24 weeks and were stratified based on previous treatments as biologic disease-modifying anti-rheumatic drug (bDMARD)-naive and bDMARD-insufficient responders (IR). Concomitant usage of methotrexate (MTX) and oral glucocorticoids (GC) was recorded. At each timepoint we recorded disease activity, laboratory parameters and adverse events. RESULTS: 126 patients were enrolled. 15.8% were bDMARD-naive (G0), while 84% were bDMARD-IR (G1). In G0, 45% of patients were in monotherapy (G2) and 55% were taken MTX (G3). In G1, 50% of patients were in monotherapy (G4) and 50% used MTX (G5).A significant reduction in all parameters at 12 weeks was observed; in the extension to 24 weeks the significant reduction was maintained for patient global assessment (PGA), examiner global assessment (EGA), visual analogue scale (VAS) pain, VAS fatigue, disease activity score (DAS)28- C-reactive protein (CRP) and CRP values. Filgotinib in monotherapy showed better outcomes in bDMARD-naive patients, with significant differences for patient reported outcomes (PROs) and DAS28-CRP. At 12 weeks, low disease activity (LDA) and remission were achieved in a percentage of 37.2 % and 10.7 % by simplified disease activity index (SDAI), 42.6 % and 5.7 % by clinical disease activity index (CDAI), 26.8 % and 25.2 % by DAS28-CRP, respectively. A significant decrease in steroid dose was evidenced in all patients. We observed a major adverse cardiovascular event in one patient and an increase in transaminase in another. No infections from Herpes Zoster were reported. CONCLUSIONS: Our real-world data confirm the effectiveness and safety of filgotinib in the management of RA, especially in bDMARD-naive patients.

Personalization of biologic therapy in patients with rheumatoid arthritis: less frequently accounted choice-driving variables.

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.

Case-control Study on Dactylitis, Enthesitis, and Anterior Uveitis in Spondyloarthritis Associated with Inflammatory Bowel Diseases: Role of Coexistent Psoriasis.

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.

Second-line biologic therapy optimization in rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis.

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.

Rapid loss of efficacy of biosimilar infliximab in three patients with Behçet's disease after switching from infliximab originator.

Three patients affected by Behçet's disease (BD) with severe uveitis and neurological involvement in stable clinical remission and who rapidly relapsed after switching from reference infliximab (re-IFX) to biosimilar infliximab (bio-IFX) are reported. In order to observe the rules of local health authorities, two males and one female (38, 26, and 40 years old, respectively) with BD complicated by severe uveitis and neuro-Behçet and who were in prolonged remission, were switched from re-IFX to bio-IFX, with the same dosing regimen of 5 mg/kg intravenous infusions every 8 weeks. All three patients experienced disease flare-ups, with recurrence of uveoretinitis in the first patient, neuro-Behçet in the second, and uveitis and neuro-Behçet in the third after 1, 3, and 2 infusions, respectively. After appropriate washout of re-IFX, all three patients were administered subcutaneous adalimumab, with a dosing regimen of 40 mg/fortnight, and a good response was achieved. Our three patients with BD experienced a rapid disease relapse after switching from re-IFX to bio-IFX, possibly due to cross-reaction of anti-IFX antibodies. This outcome suggests the necessity to exercise caution regarding the automatic substitution of re-IFX with bio-IFX in patients achieving remission with re-IFX.

Tailored first-line biologic therapy in patients with rheumatoid arthritis, spondyloarthritis, and psoriatic arthritis.

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.

Uveitis in Spondyloarthritis: An Overview.

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.

Systemic autoimmune disease in asbestosis rapidly responding to anti-interleukin-1beta antibody canakinumab: a case report.

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.

Efficacy and safety of rituximab with and without methotrexate in the treatment of rheumatoid arthritis patients: results from the GISEA register.

INTRODUCTION: Rituximab (RTX) is a monoclonal anti-CD20 antibody approved for the treatment of rheumatoid arthritis (RA) in association with methotrexate (MTX). OBJECTIVES: To evaluate the efficacy and safety of RTX-MTX combination therapy compared with RTX alone in the treatment of RA. METHODS: We analyzed data from a prospective cohort study, the Italian biologic register GISEA, to investigate the efficacy and safety of rituximab. Moreover, the adverse events (AE) and the causes of discontinuation therapy were analyzed. RESULTS: We identified 338 RA patients, 162 treated with RTX and 176 with RTX-MTX. After 52 and 104 weeks of therapy the disease activity score in 28 joints and the Health Assessment Questionnaire Score were available in 168 patients (78 with RTX-MTX and 60 with RTX alone), showing significant reduction without differences among the two groups. AE were reported in 142 patients (42%), for a total of 368 recorded side effects. The majority (90.5%) of AE were mild to moderate in severity. Comparable percentages of severe AE were reported in the 2 groups (9.9% for RTX alone and 9.3% for RTX+MTX). A poor disease control was observed in 14.2% and 13.5% of patients treated with RTX+MTX and RTX, respectively; while 12 patients (4.5% in RTX+MTX, and 2.5% in RTX group) suspended therapy for AE. CONCLUSIONS: RTX showed a good efficacy and safety profile in the real-life management of RA patients regardless of the association with MTX.

Duration of remission after halving of the etanercept dose in patients with ankylosing spondylitis: a randomized, prospective, long-term, follow-up study.

BACKGROUND: The aim of this study was to evaluate the proportion of patients with ankylosing spondylitis maintaining clinical remission after reduction of their subcutaneous etanercept dose to 50 mg every other week compared with that in patients receiving etanercept 50 mg weekly. METHODS: In the first phase of this randomized, prospective, follow-up study, all biologic-naïve patients identified between January 2005 and December 2009 as satisfying the modified New York clinical criteria for ankylosing spondylitis treated with etanercept 50 mg weekly were evaluated for disease remission in January 2010. In the second phase, patients meeting the criteria for remission were randomized to receive subcutaneous etanercept as either 50 mg weekly or 50 mg every other week. The randomization allocation was 1:1. Remission was defined as Bath Ankylosing Spondylitis Disease Activity Index < 4, no extra-axial manifestations of peripheral arthritis, dactylitis, tenosynovitis, or iridocyclitis, and normal acute-phase reactants. The patients were assessed at baseline, at weeks 4 and 12, and every 12 weeks thereafter. The last visit constituted the end of the follow-up. RESULTS: During the first phase, 78 patients with ankylosing spondylitis (57 males and 21 females, median age 38 years, median disease duration 12 years) were recruited. In January 2010, after a mean follow-up of 25 ± 11 months, 43 (55.1%) patients achieving clinical remission were randomized to one of the two treatment arms. Twenty-two patients received etanercept 50 mg every other week (group 1) and 21 received etanercept 50 mg weekly (group 2). At the end of follow-up, 19 of 22 (86.3%) subjects in group 1 and 19 of 21 (90.4%) in group 2 were still in remission, with no significant difference between the two groups. The mean follow-up duration in group 1 and group 2 was 22 ± 1 months and 21 ± 1.6 months, respectively. CONCLUSION: Remission of ankylosing spondylitis is possible in at least 50% of patients treated with etanercept 50 mg weekly. After halving of the etanercept dose, remission is maintained in a high percentage of patients during long-term follow-up, with important economic implications.

Frequency of iridocyclitis in patients with early psoriatic arthritis: a prospective, follow up study.

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.

Sustained maintenance of clinical remission after adalimumab dose reduction in patients with early psoriatic arthritis: a long-term follow-up study.

PURPOSE: 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.

Infliximab in psoriatic arthritis.

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.

Efficacy of infliximab in refractory Behçet's disease-associated and idiopathic posterior segment uveitis: a prospective, follow-up study of 50 patients.

PURPOSE: 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.

Frequency of anemia of inflammation in patients with ankylosing spondylitis requiring anti-TNFα drugs and therapy-induced changes.

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: a systematic review.

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.

Criteria, frequency, and duration of clinical remission in psoriatic arthritis patients with peripheral involvement requiring second-line drugs.

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 (p < 0.001). 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 (p < 0.001). 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.

Single-center series and systematic review of randomized controlled trials of malignancies in patients with rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis receiving anti-tumor necrosis factor alpha therapy: is there a need for more comprehensive screening procedures?

OBJECTIVE: To systematically review the occurrence of malignancies among patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), and ankylosing spondylitis (AS) treated with anti-tumor necrosis factor alpha (anti-TNFalpha) therapy in randomized controlled trials (RCTs), and to report a retrospective personal case series evaluating the frequency of malignancies in patients with RA, PsA, and AS requiring anti-TNF therapy selected with more comprehensive cancer screening procedures compared with patients screened according to previously published procedures. METHODS: The primary outcome was the report of frequency of malignancies in RCTs and the latency between the therapy introduction and the occurrence of the neoplasm. A total of 363 consecutive RA, PsA, and AS patients requiring anti-TNF therapy from 2002 to 2006 observed at the Rheumatology Unit in Prato, Italy, underwent extensive cancer screening procedures. An historical controlled group of 73 patients treated between January 1999 and December 2001 underwent the screening procedures accepted for the RCT procedures. RESULTS: Thirty-six RCTs were included for analysis. Malignancies occurred in 60 (0.75%) of 8,015 patients randomized to the active treatment arm and in 21 (0.52%) of 3,991 patients in the placebo arms (P = 0.15). In the personal retrospective case series, 1 study patient (0.27%) and 3 controls (4.1%) developed cancer over the followup period (P = 0.017). Mean +/- SD followup duration was 40.9 +/- 16.7 months in study patients and 50.6 +/- 18.1 months in controls. CONCLUSION: The results of RCTs and our data showing 26% of malignancies occurring within 12 weeks from enrollment suggest the need for a revision of current cancer screening procedures in RCTs and in clinical practice.

Clinical and ultrasonographic monitoring of response to adalimumab treatment in rheumatoid arthritis.

OBJECTIVE: To evaluate by clinical, laboratory, and sonographic assessment the effects of adalimumab therapy in patients with rheumatoid arthritis (RA) over 24 months of treatment. METHODS: Twenty-five patients with RA were commenced on adalimumab therapy. Before the beginning of the therapy (Time 0) and after 3 (T1), 12 (T2), and 24 (T3) months we evaluated erythrocyte sedimentation rate, C-reactive protein, physician and patient visual analog scale for disease activity, number of tender and swollen joints, Health Assessment Questionnaire, and Disease Activity Score in 28 joints. In addition, musculoskeletal ultrasound (US) was performed bilaterally in the 2nd and 5th metacarpophalangeal, 3rd interphalangeal, wrist, and knee joints and in the tendon sheaths and bursae of those areas. A semiquantitative score (0 3) was used to indicate the presence of a localized inflammatory process and/or structural damage. The summed total was used as an indicator of global change in each joint (single joint score). The sum of the single joint scores was used as an indicator of overall polyarticular involvement in each patient (total score). RESULTS: Patients who did not submit to the planned examinations strictly on time were excluded from the study. Then 25 patients were examined at T0 and T1, 20 at T2, and 9 at T3. All clinical and laboratory measures as well as the US scores were significantly reduced during the followup. CONCLUSION: A positive response to treatment with adalimumab was demonstrated by clinical, laboratory, and US evaluation by both short- and longterm followup.

Isolated knee monoarthritis heralding resectable non-small-cell lung cancer. A paraneoplastic syndrome not previously described.

OBJECTIVE: To describe isolated knee monoarthritis as a paraneoplastic syndrome heralding non-small cell lung cancer (NSCLC), and to discuss its clinical characteristics. METHODS: Clinical records of all consecutive, new outpatients with isolated knee monoarthritis observed from January 2000 to December 2005 were reviewed. A systematic review of Medline and Cochrane Library databases was performed to identify English-language articles related to rheumatological paraneoplastic syndromes associated with NSCLC. RESULTS: Over 6 years, 6654 new outpatients with different rheumatic disorders were observed. Of these, 296 (4.4%) presented with isolated monoarthritis of the knee. In five out of 296 patients (1.7%) this feature represented the initial manifestation of NSCLC. All five patients were middle-aged men, with a long history of heavy cigarette smoking, who had a non-erosive, 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 five patients are in good condition after a median follow up of 41 months. The literature review revealed that paraneoplastic knee monoarthritis has not previously been reported. CONCLUSION: Knee monoarthritis may in some cases represent a paraneoplastic syndrome heralding NSCLC at an early stage.