Age at diagnosis influences the clinical phenotype, treatment strategies and outcomes in patients with giant cell arteritis: results from the observational GCAGE study on a large cohort of 1004 patients.

BACKGROUND: Immune and vascular ageing are proposed risk factors for giant cell arteritis (GCA). Data on the impact of age at diagnosis of GCA on the clinical presentation and course of the disease are scarce. METHODS: Patients with GCA followed at referral centres within the Italian Society of Rheumatology Vasculitis Study Group were enrolled up to November 2021. Patients were grouped according to age at diagnosis: ≤64, 65-79 and ≥80 years old. RESULTS: The study included 1004 patients, mean age 72.1±8.4, female 70.82%. Median follow-up duration was 49 (IQR 23-91) months. Patients in the oldest group (≥80 years) had significantly more cranial symptoms, ischaemic complications and risk for blindness compared with the groups 65-79 and ≤64 years (blindness: 36.98% vs 18.21% vs 6.19%; p<0.0001). Large-vessel-GCA was more frequent in the youngest group (65% of patients). Relapses occurred in 47% of patients. Age did not influence the time to first relapse, nor the number of relapses. Older age was negatively associated with the number of adjunctive immunosuppressants. Patients >65 years old had 2-3 fold increased risk for aortic aneurysm/dissection up to 60 months follow-up. Serious infections, but not other treatment-related complications (hypertension, diabetes, osteoporotic fractures), were significantly associated with older age. Mortality occurred in 5.8% of the population with age >65, cranial and systemic symptoms as independent risk factors. CONCLUSIONS: The highest risk of ischaemic complications, aneurysm development, serious infections and the possible undertreatment make of GCA a very challenging disease in the oldest patients.

Interstitial lung disease in microscopic polyangiitis and granulomatosis with polyangiitis: demographic, clinical, serological and radiological features of an Italian cohort from the Italian Society for Rheumatology.

OBJECTIVES: Interstitial lung disease (ILD) has been described as a possible pulmonary involvement in antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitides (AAV), mainly granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA). Aim of this cross-sectional Italian national study was to describe demographic, clinical and serological profile of ILD related to MPA and GPA and investigate possible correlations between radiologic patterns of ILD and vasculitis features. METHODS: We enrolled 95 consecutive patients with AAV-ILD, 56 affected by MPA (58.9%) and 39 by GPA (41.1%). RESULTS: NSIP was the most frequently detected ILD pattern, observed in c-ANCA patients in 60.9% of cases, followed by UIP pattern mainly observed in p-ANCA patients (47.7%, p=0.03). ILD represented the first clinical manifestation, preceding vasculitis diagnosis in 22.1% of cases and, globally, ILD was already detectable at AAV diagnosis in 66.3% of patients. The diagnosis of ILD preceded that of AAV in 85.7% of p-ANCA positive-patients, while only one patient with c-ANCA developed ILD before AAV (p= 0.039). Multivariate analysis confirmed the correlation of UIP pattern with p-ANCA-positivity and a diagnosis of ILD before AAV, also when adjusted for age and sex. CONCLUSIONS: Our study confirms that UIP is a frequent pattern of lung disease in AAVILD patients. Our results also suggest that ILD can represent an early complication of AAV but also occur in the course of the disease, suggesting the need of a careful evaluation by both pulmonologist and rheumatologist to achieve an early diagnosis. Further prospective studies are needed to define ILD prevalence and evolution in AAV patients.

Clinical spectrum time course in non-Asian patients positive for anti-MDA5 antibodies.

OBJECTIVES: To define the clinical spectrum time-course and prognosis of non-Asian patients positive for anti-MDA5 antibodies. METHODS: We conducted a multicentre, international, retrospective cohort study. RESULTS: 149 anti-MDA5 positive patients (median onset age 53 years, median disease duration 18 months), mainly females (100, 67%), were included. Dermatomyositis (64, 43%) and amyopathic dermatomyositis (47, 31%), were the main diagnosis; 15 patients (10%) were classified as interstitial pneumonia with autoimmune features (IPAF) and 7 (5%) as rheumatoid arthritis. The main clinical findings observed were myositis (84, 56%), interstitial lung disease (ILD) (108, 78%), skin lesions (111, 74%), and arthritis (76, 51%). The onset of these manifestations was not concomitant in 74 cases (50%). Of note, 32 (21.5%) patients were admitted to the intensive care unit for rapidly progressive-ILD, which occurred in median 2 months from lung involvement detection, in the majority of cases (28, 19%) despite previous immunosuppressive treatment. One-third of patients (47, 32% each) was ANA and anti-ENA antibodies negative and a similar percentage was anti-Ro52 kDa antibodies positive. Non-specific interstitial pneumonia (65, 60%), organising pneumonia (23, 21%), and usual interstitial pneumonia-like pattern (14, 13%) were the main ILD patterns observed. Twenty-six patients died (17%), 19 (13%) had a rapidly progressive-ILD. CONCLUSIONS: The clinical spectrum of the anti-MDA5 antibodies-related disease is heterogeneous. Rapidly-progressive ILD deeply impacts the prognosis also in non-Asian patients, occurring early during the disease course. Anti-MDA5 antibody positivity should be considered even when baseline autoimmune screening is negative, anti-Ro52 kDa antibodies are positive, and radiology findings show a NSIP pattern.

Risk of Tuberculosis Reactivation in Patients with Rheumatoid Arthritis, Ankylosing Spondylitis, and Psoriatic Arthritis Receiving Non-Anti-TNF-Targeted Biologics.

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.

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.

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.

2012 Provisional classification criteria for polymyalgia rheumatica: a European League Against Rheumatism/American College of Rheumatology collaborative initiative.

The objective of this study was to develop European League Against Rheumatism/American College of Rheumatology classification criteria for polymyalgia rheumatica (PMR). Candidate criteria were evaluated in a 6-month prospective cohort study of 125 patients with new-onset PMR and 169 non-PMR comparison subjects with conditions mimicking PMR. A scoring algorithm was developed based on morning stiffness >45 minutes (2 points), hip pain/limited range of motion (1 point), absence of rheumatoid factor and/or anti-citrullinated protein antibody (2 points), and absence of peripheral joint pain (1 point). A score ≥4 had 68% sensitivity and 78% specificity for discriminating all comparison subjects from PMR. The specificity was higher (88%) for discriminating shoulder conditions from PMR and lower (65%) for discriminating RA from PMR. Adding ultrasound, a score ≥5 had increased sensitivity to 66% and specificity to 81%. According to these provisional classification criteria, patients ≥50 years old presenting with bilateral shoulder pain, not better explained by an alternative pathology, can be classified as having PMR in the presence of morning stiffness >45 minutes, elevated C-reactive protein and/or erythrocyte sedimentation rate, and new hip pain. These criteria are not meant for diagnostic purposes.

In inflammatory myopathies, dropped head/bent spine syndrome is associated with scleromyositis: an international case-control study.

BACKGROUND: Some myopathies can lead to dropped head or bent spine syndrome (DH/BS). The significance of this symptom has not been studied in inflammatory myopathies (IM). OBJECTIVES: To assess the significance of DH/BS in patients with IM. METHODS: Practitioners from five IM networks were invited to report patients with IM suffering from DH/BS (without other known cause than IM). IM patients without DH/BS, randomly selected in each participating centre, were included as controls at a ratio of 2 to 1. RESULTS: 49 DH/BS-IM patients (DH: 57.1%, BS: 42.9%) were compared with 98 control-IM patients. DH/BS-IM patients were older (65 years vs 53 years, p<0.0001) and the diagnosis of IM was delayed (6 months vs 3 months, p=0.009). Weakness prevailing in the upper limbs (42.9% vs 15.3%), dysphagia (57.1% vs 25.5%), muscle atrophy (65.3% vs 34.7%), weight loss (61.2% vs 23.5%) and loss of the ability to walk (24.5% vs 5.1%) were hallmarks of DH/BS-IM (p≤0.0005), for which the patients more frequently received intravenous immunoglobulins (65.3% vs 34.7%, p=0.0004). Moreover, DH/BS-IM patients frequently featured signs and/or complications of systemic sclerosis (SSc), fulfilling the American College of Rheumatology/European Alliance of Associations for Rheumatology criteria for this disease in 40.8% of the cases (vs 5.1%, p<0.0001). Distribution of the myopathy, its severity and its association with SSc were independently associated with DH/BS (p<0.05). Mortality was higher in the DH/BS-IM patients and loss of walking ability was independently associated with survival (p<0.05). CONCLUSION: In IM patients, DH/BS is a marker of severity and is associated with SSc (scleromyositis).

2012 provisional classification criteria for polymyalgia rheumatica: a European League Against Rheumatism/American College of Rheumatology collaborative initiative.

The objective of this study was to develop EULAR/ACR classification criteria for polymyalgia rheumatica (PMR). Candidate criteria were evaluated in a 6-month prospective cohort study of 125 patients with new onset PMR and 169 non-PMR comparison subjects with conditions mimicking PMR. A scoring algorithm was developed based on morning stiffness >45 minutes (2 points), hip pain/limited range of motion (1 point), absence of RF and/or ACPA (2 points), and absence of peripheral joint pain (1 point). A score ≥4 had 68% sensitivity and 78% specificity for discriminating all comparison subjects from PMR. The specificity was higher (88%) for discriminating shoulder conditions from PMR and lower (65%) for discriminating RA from PMR. Adding ultrasound, a score ≥5 had increased sensitivity to 66% and specificity to 81%. According to these provisional classification criteria, patients ≥50 years old presenting with bilateral shoulder pain, not better explained by an alternative pathology, can be classified as having PMR in the presence of morning stiffness>45 minutes, elevated CRP and/or ESR and new hip pain. These criteria are not meant for diagnostic purposes.

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.

Incidence and mortality of interstitial lung disease in rheumatoid arthritis: a population-based study.

OBJECTIVE: Interstitial lung disease (ILD) has been recognized as an important comorbidity in rheumatoid arthritis (RA). We undertook the current study to assess incidence, predictors, and mortality of RA-associated ILD. METHODS: We examined a population-based incidence cohort of patients with RA and a matched cohort of individuals without RA. All subjects were followed up longitudinally. The lifetime risk of ILD was estimated. Cox proportional hazards models were used to compare the incidence of ILD between cohorts, to investigate predictors, and to explore the impact of ILD on survival. RESULTS: Patients with RA (n = 582) and subjects without RA (n = 603) were followed up for a mean of 16.4 and 19.3 years, respectively. The lifetime risk of developing ILD was 7.7% for RA patients and 0.9% for non-RA subjects. This difference translated into a hazard ratio (HR) of 8.96 (95% confidence interval [95% CI] 4.02-19.94). The risk of developing ILD was higher in RA patients who were older at the time of disease onset, in male patients, and in individuals with more severe RA. The risk of death for RA patients with ILD was 3 times higher than in RA patients without ILD (HR 2.86 [95% CI 1.98-4.12]). Median survival after ILD diagnosis was only 2.6 years. ILD contributed approximately 13% to the excess mortality of RA patients when compared with the general population. CONCLUSION: Our results emphasize the increased risk of ILD in patients with RA. The devastating impact of ILD on survival provides evidence that development of better strategies for the treatment of ILD could significantly lower the excess mortality among individuals with RA.

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.

Association of Smoking and Obesity on the Risk of Developing Primary Sjögren Syndrome: A Population-based Cohort Study.

OBJECTIVE: To explore the role of smoking and obesity in primary Sjögren syndrome (pSS). METHODS: Olmsted County (Minnesota, USA) residents (n = 106) diagnosed with pSS from 2000 to 2015 were compared to 3 controls without pSS and matched for age and sex who were randomly selected from Olmsted County residents. RESULTS: Current smokers were less likely to be pSS cases (OR 0.34, 95% CI 0.14-0.85), while there was no association between former smoking and case/control status (OR 1.27, 95% CI 0.80-2.03) compared to never smokers. Smoking status was not associated with antinuclear antibody, anti-SSA, anti-SSB, or rheumatoid factor positivity (p > 0.05). OR for obesity was 0.79 (95% CI 0.48-1.30). CONCLUSION: In this population-based study, current smoking was inversely associated with case/control status, while body mass index lacked any association.

Effectiveness of Adalimumab for the Treatment of Psoriatic Arthritis: An Italian Real-Life Retrospective Study.

Background: Few studies have evaluated the effectiveness of adalimumab in the real-life setting in psoriatic arthritis (PsA). Objective: To evaluate the 2-year retention rate of adalimumab in PsA patients. Potential baseline parameters influencing persistence on treatment were also evaluated. Methods: PsA patients from 16 Italian Rheumatology Units treated with adalimumab as first- or second-line biological therapy were retrospectively evaluated. Adalimumab retention rate was evaluated at 12 and 24 months. Logistic regression was used to evaluate the association between predictor variables and adalimumab retention rate. Results: From 424 patients (53.5% male, aged 48.3 ± 12.8 years) who started treatment with adalimumab, 367 (86.6%) maintained treatment for 12 months and 313 (73.8%) for 2 years. At 24-months, Disease Activity in PsA (DAPSA) remission (defined as ≤4) and Low Disease Activity (LDA) (≤14) were achieved in 22.8% and 44.4% of patients, respectively. Adalimumab treatment significantly decreased the number of tender (7.0 ± 5.7 at baseline vs. 2.3 ± 3.5 at 24 months, p < 0.001) and swollen joints (2.7 ± 2.8 at baseline vs. 0.4 ± 0.9 at 24 months, p < 0.001), DAPSA (25.5 ± 10.9 at baseline vs. 11.0 ± 8.4 at 24 months, p < 0.001), PASI (5.3 ± 5.7 at baseline vs. 2.7 ± 2.8 at 24 months, p < 0.001) and CRP (3.8 ± 6.3 at baseline vs. 1.2 ± 1.7 at 24 months, p < 0.001). Among a range of laboratory and clinical variables, only female gender was associated with improved adalimumab persistence at 24 months (OR: 1.98, 95% CI: 1.2-3.2, p = 0.005). Conclusions: Independent of a range of predictor variables, adalimumab was shown to be effective, while maintaining a high retention rate after 2 years in PsA patients.

Diagnosis and treatment of giant cell arteritis.

Giant cell arteritis (GCA) is a chronic granulomatous vasculitis of unknown aetiology occurring in the elderly. It affects the cranial branches of the arteries originating from the aortic arch and is usually associated with markedly elevated acute-phase reactants. In 10-15% of cases the extra-cranial branches of the aortic arch are involved. GCA is closely related to polymyalgia rheumatica (PMR), although the relationship between the two disorders is still unclear. New-onset headache, scalp tenderness, jaw claudication, temporal artery abnormalities on physical examination, visual symptoms and associated PMR represent the most typical and frequent features of the disease. Systemic manifestations, including fever, anorexia and weight loss, are observed in 50% of cases. Less frequent manifestations are related to the central or peripheral nervous systems, the respiratory tract and extra-cranial large-vessel involvement. As GCA is characterized by a wide spectrum of clinical manifestations, it is important to recognize the different onset patterns of the disease and related diagnostic steps. The diagnosis is relatively straightforward in the presence of typical cranial manifestations, but it may be challenging in the case of a normal erythrocyte sedimentation rate, occult GCA or in patients with isolated extra-cranial features. Temporal artery biopsy still represents the gold standard for diagnosis, while the role of ultrasonography, high-resolution magnetic resonance imaging and positron emission tomography should be better addressed. Corticosteroids remain the therapy of choice. Data supporting the usefulness of antiplatelet agents and anticoagulants combined with corticosteroids to prevent ischaemic complications as well as the corticosteroid-sparing effect of methotrexate and anti-tumour necrosis factor-alpha drugs are limited and non-conclusive.

Preventive therapy for tuberculosis in rheumatological patients undergoing therapy with biological drugs.

INTRODUCTION: 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.

Hospitalisation rates among patients with primary Sjögren's syndrome: a population-based study, 1995-2016.

OBJECTIVE: To determine rates and primary discharge diagnoses of hospitalisation in a cohort of patients with incident primary Sjögren's syndrome (pSS) compared with the general population. METHODS: This was a retrospective population-based cohort study focused on Olmsted County, Minnesota. The pSS cohort consisted of patients with incident pSS in the 1976-2015 period and was compared with a cohort of individuals without pSS matched 3:1 for age, sex and calendar year, randomly selected from the same population. Hospitalisations in 1995-2016 were examined. Discharge diagnoses were categorised using the Clinical Classifications Software for International Classification of Diseases, 9th revision, Clinical Modification. RESULTS: A total of 385 hospitalisations occurred in the 160 patients with pSS during 1592 person-years of follow-up. Among 466 comparators, there were 899 hospitalisations during 4660 person-years of follow-up, resulting in a significantly higher rate of hospitalisations in patients with pSS (rate ratio (RR): 1.25, 95% CI: 1.11 to 1.41). Rates of hospitalisation were increased among patients with pSS for endocrine, nutritional and metabolic diseases and immunity disorders (RR 1.82, 95% CI 1.08 to 2.98), diseases of the musculoskeletal system and connective tissue (RR 1.49, 95% CI 1.05 to 2.05) and for injuries and poisoning (RR 1.46, 95% CI 1.01 to 2.06). While not significantly increased overall, hospitalisations for diseases of the circulatory system were significantly increased in patients with pSS aged ≥75 years (RR 1.54, 95% CI 1.11 to 2.11). CONCLUSIONS: Patients with pSS experienced higher rates of hospitalisation than the general population. Hospitalisations for endocrine/metabolic disorders, diseases of the circulatory system, diseases of the musculoskeletal system and connective tissue disorders, and injuries were more common among patients with pSS than comparators.

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.

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.