Effectiveness of ixekizumab over 24 months in different clinical scenarios in psoriatic arthritis: results from the Gruppo Italiano Studio Early Arthritis multicentric prospective registry.

OBJECTIVES: We aimed to evaluate ixekizumab (IXE) effectiveness, drug survival and clinical response predictors in moderate-severe psoriatic arthritis (PsA) patients in different clinical scenarios. METHODS: This was a multicentre real-life observational study based on Gruppo Italiano Studio Early Arthritis (GISEA) registry of IXE treatment in PsA patients (January 2019-June 2023). Data were collected at baseline and every six months. RESULTS: 223 PsA outpatients were included. Statistically significant improvement was observed after 6 (T6), 12 (T12) and 24 (T24) months of therapy for tender and swollen joint count (TJC and SJC), Visual Analogue Scale (VAS)-pain and Disease Activity in PSoriatic Arthritis (DAPSA) score. DAPSA remission was reached at T12 in 22% and at T24 in 18.5% of patients. At baseline, higher fibromyalgia and combination therapy with conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) in females with respect to males and higher Psoriasis Area Severity Index (PASI) in males than in females were observed. Therapeutic effectiveness showed in males higher DAPSA and VAS-pain reduction, higher percentage of males in DAPSA remission/low disease activity (LDA) at T6, and higher ∆PASI at T6 and T12 than in female patients. At multivariate analysis, male sex was predictive for treatment response at T6 [p=0.02, odds ratio (OR) 2.49 (95% confidence interval 1.11-5.54)], while it lost significance at T12. CONCLUSIONS: IXE effectiveness was highlighted after 6 months at both joint and skin levels and lasted up to 24 months in different clinical scenarios, making IXE effective in the complexity of managing PsA in a real-life setting.

Retention rate of biologic and targeted synthetic anti-rheumatic drugs in elderly rheumatoid arthritis patients: data from GISEA registry.

Objectives: An increased number of elderly individuals affected by rheumatoid arthritis (RA) has been reported, including both patients with RA onset in advanced age and patients aged with the disease. In this registry-based study, we aimed to analyze the retention rate and cause of discontinuation of biologic (b) and targeted synthetic (ts)-disease-modifying anti-rheumatic drugs (DMARDs) in RA patients over 65 year old. Methods: RA patients enrolled in the Italian GISEA registry and starting a b- or a ts-DMARD over 65 years of age were included. Demographic, clinical, serologic, and therapeutic features were collected. Results: A total of 1,221 elderly RA patients were analyzed (mean age 71.6 ± 5.2 years). RA was diagnosed before 65 years in 72.5% of cases, a 60.6% of patients experienced a previous b- or ts-DMARD. In patients older than 65 initiating a new b- or ts-DMARDS, tumor necrosis factor alpha inhibitors (TNFi) were prescribed in 29.6% of patients, abatacept in 24.8%, anti-interleukin 6 receptor antagonists (anti-IL6R) in 16.3%, Janus kinases inhibitors (JAKi) in 24.9%, and rituximab in 4.4%. The main causes of discontinuation were primary or secondary inadequate responses (66.1%). The median retention rate for all treatments was 181.3 weeks. A statistically higher retention rate was observed for abatacept when compared to TNFi (p = 0.02), JAKi (p < 0.001), and anti-IL6R (p < 0.001), and for TNFi vs. JAKi (p = 0.013). Conclusion: We described, in a real-life setting, elderly RA patients treated with a biologic or a ts-DMARD in Italy. Loss of efficacy was the main cause of discontinuation, and the DMARD safety profile suggests that age does not contraindicate their use. Our study reinforced that the control of disease activity is mandatory.

CXCL-13 serum levels in patients with rheumatoid arthritis treated with abatacept.

OBJECTIVES: C-X-C motif chemokine 13 (CXCL-13), which is expressed by synovial follicular dendritic cells and activated mature antigen-experienced T-helper cells, has been described as a surrogate marker of lymphoid phenotype of synovitis in rheumatoid arthritis (RA). A preferential response to anti-interleukin-6 receptor (IL-6R) as compared to anti-tumour necrosis factor alpha (TNFα) monotherapy has been described in patients with increased levels of CXCL-13. We hypothesised that serum levels of CXCL-13 could be used as a biomarker of response to treatment with abatacept (ABA), a T-cell co-stimulation blocker. METHODS: Serum levels of CXCL-13 and of soluble intracellular adhesion molecule 1 (sICAM-1) (a putative marker of the myeloid subtype of synovitis) were measured by indirect solid-phase enzyme immunoassays, before (T0) and after 6 months of therapy with ABA (T6) in 63 patients with RA. Circulating T follicular helper cells and B cell subpopulations were identified by flow-cytometry. RESULTS: At T0, CXCL-13 serum levels were higher in RA patients than in healthy controls (p=0.0001) and correlated with disease activity, while no difference between the two groups was observed as far as sICAM-1 levels. Serum levels of CXCL-13 levels decreased after therapy with ABA both in patients who achieved a clinical response (p<0.01) and in non-responders (p=0.01), whereas sICAM-1 levels did not significantly change. When comparing RA patients who responded to ABA with non-responders no significant difference of baseline serum levels of CXCL-13 was observed. CONCLUSIONS: CXCL-13 serum levels are raised in RA patients and decrease after therapy with ABA. We were not able to demonstrate that serum CXCL-13 levels predict the clinical response to ABA in RA patients.

Retention rate of a second line with a biologic DMARD after failure of a first-line therapy with abatacept, tocilizumab, or rituximab: results from the Italian GISEA registry.

OBJECTIVES: EULAR recommendations do not suggest which biologic disease-modifying anti-rheumatic drug (bDMARD) should be preferred after failure of a first bDMARD in the treatment of rheumatoid arthritis (RA). In particular, few data are available regarding the effectiveness of a second-line bDMARD after failure of abatacept (ABA), tocilizumab (TCZ), and rituximab (RTX). The aim of this study was to analyze the retention rate of a second line with tumor necrosis factor inhibitors (TNFi) or other mechanisms of action (MoAs), after the failure of either RTX, TCZ, or ABA. METHODS: Two hundred and seventy-eight RA patients from the Italian GISEA registry were included in the study. RTX was the first bDMARD in 18% of patients, ABA in 45.7%, and TCZ in 36.3%, while the second bDMARD was a TNFi (group 1) in 129 patients and an agent with a different MoA (group 2) in 149. RESULTS: During a median follow-up of 22 months (IQR 68), 129 patients discontinued their treatment; patients of group 1 discontinued the treatment more frequently than patients of group 2 (p<0.001) with retention rates of 33.6±5.7% and 63.6±4.6% after 104 weeks for group 1 and group 2, respectively (p<0.001). At multivariate analysis, the mechanism of action was the only predictor for the maintenance in therapy. CONCLUSIONS: According to our data, ABA, RTX, and TCZ seem to maintain a good retention rate also when used as a second-line therapy, suggesting their use after the failure of a non-TNFi as first-line therapy. However, specifically designed studies are needed to evaluate the more appropriate therapeutic strategies in RA, according to the first-line drug, including new targeted synthetic DMARDs. Key Points • A large proportion of rheumatoid arthritis patients fail the first biologic DMARD. • Few data are available about the efficacy of biologic DMARD after the failure of a non-TNF inhibitor. • Abatacept, rituximab, or tocilizumab seem to maintain a good retention rate after the failure of a first-course therapy with a non-TNF inhibitor.

Tocilizumab for the treatment of severe COVID-19 pneumonia with hyperinflammatory syndrome and acute respiratory failure: A single center study of 100 patients in Brescia, Italy.

A hyperinflammatory syndrome (HIS) may cause a life-threatening acute respiratory distress syndrome (ARDS) in patients with COVID-19 pneumonia. A prospective series of 100 consecutive patients admitted to the Spedali Civili University Hospital in Brescia (Italy) between March 9th and March 20th with confirmed COVID-19 pneumonia and ARDS requiring ventilatory support was analyzed to determine whether intravenous administration of tocilizumab (TCZ), a monoclonal antibody that targets the interleukin 6 (IL-6) receptor, was associated with improved outcome. Tocilizumab was administered at a dosage of 8 mg/kg by two consecutive intravenous infusions 12 h apart. A third infusion was optional based on clinical response. The outcome measure was an improvement in acute respiratory failure assessed by means of the Brescia COVID Respiratory Severity Score (BCRSS 0 to 8, with higher scores indicating higher severity) at 24-72 h and 10 days after tocilizumab administration. Out of 100 treated patients (88 M, 12 F; median age: 62 years), 43 received TCZ in the intensive care unit (ICU), while 57 in the general ward as no ICU beds were available. Of these 57 patients, 37 (65%) improved and suspended noninvasive ventilation (NIV) (median BCRSS: 1 [IQR 0-2]), 7 (12%) patients remained stable in NIV, and 13 (23%) patients worsened (10 died, 3 were admitted to ICU). Of the 43 patients treated in the ICU, 32 (74%) improved (17 of them were taken off the ventilator and were discharged to the ward), 1 (2%) remained stable (BCRSS: 5) and 10 (24%) died (all of them had BCRSS≥7 before TCZ). Overall at 10 days, the respiratory condition was improved or stabilized in 77 (77%) patients, of whom 61 showed a significant clearing of diffuse bilateral opacities on chest x-ray and 15 were discharged from the hospital. Respiratory condition worsened in 23 (23%) patients, of whom 20 (20%) died. All the patients presented with lymphopenia and high levels of C-reactive protein (CRP), fibrinogen, ferritin and IL-6 indicating a HIS. During the 10-day follow-up, three cases of severe adverse events were recorded: two patients developed septic shock and died, one had gastrointestinal perforation requiring urgent surgery and was alive at day 10. In conclusion, our series showed that COVID-19 pneumonia with ARDS was characterized by HIS. The response to TCZ was rapid, sustained, and associated with significant clinical improvement.

Two-year persistence of golimumab as second-line biologic agent in rheumatoid arthritis as compared to other subcutaneous tumor necrosis factor inhibitors: real-life data from the LORHEN registry.

OBJECTIVES: To evaluate the 2-year retention rate of golimumab compared with etanercept and adalimumab as second-line biologic agent in rheumatoid arthritis (RA) patients who failed a previous tumor necrosis factor inhibitor (TNFi). METHODS: Data on RA patients treated with a second-line subcutaneous TNFi were extracted from a multicentric Italian cohort (the LORHEN registry). The analysis was limited to etanercept, adalimumab and golimumab in the period when all were available in Italy (since October 2010). The 2-year retention rate was calculated by Kaplan-Meier method and the comparative risk for discontinuation among individual TNFi was compared by a stratified log-rank test. RESULTS: One hundred and ninety-five RA patients treated with etanercept (n = 76), adalimumab (n = 68) or golimumab (n = 51) were included in the analysis. The 2-year retention rate (40% with a median time-on-drug of 12.9 months in the whole population) was significantly lower for adalimumab (31.2%, P = 0.018) and numerically lower for etanercept (39.8%, P = 0.068) compared with golimumab (53.4%) because of a higher discontinuation rate due to adverse events (P = 0.042 and P = 0.038 versus golimumab, respectively). Drug survival was greater in concomitant synthetic disease modifying anti-rheumatic drug (sDMARD) users (44.2%) compared with TNFi monotherapy (22.5%, P = 0.036). No difference was found in survival analysis according to first-line TNFi reason for discontinuation and pattern of TNFi switch (antibody-receptor, antibody-antibody or receptor-antibody). CONCLUSIONS: Our real-life data confirmed switching to a second TNFi as a good option for treating first-line TNFi failures in RA, especially in combination with sDMARDs. Second-line golimumab showed an overall better 2-year drug survival compared with adalimumab and etanercept.

Two-year retention rate of golimumab in rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis: data from the LORHEN registry.

OBJECTIVES: We aimed to provide data on golimumab real-life use in rheumatoid arthritis (RA), psoriatic arthritis (PsA) and ankylosing spondylitis (AS) from a multicentre observational registry of Northern Italy. METHODS: We extracted data of patients who started treatment with golimumab from October 2010, and who had at least one follow-up visit. Data were analysed until a maximum follow-up of 24 months. The two-year retention rate in the three diseases was assessed with Kaplan-Meier estimators. To compare crude survival between diagnoses and lines of treatment we used the log-rank test, while Cox proportional hazard models were used to adjust for confounders. RESULTS: Overall, 410 subjects were included: 180 patients with RA, 110 with PsA and 120 with AS. The two-year retention rate of patients with RA was 47.3%, 48% for PsA, and 62.8% for AS. Crude survival on treatment of patients with AS was significantly higher than that of RA patients (p=0.032), while no significant difference was found between AS and PsA and between RA and PsA. In patients with RA, subjects treated with concomitant sDMARDs showed a lower discontinuation rate than those receiving golimumab alone. The comparison between first and second line of treatment groups did not show any significant difference in mean survival time in patients with RA, PsA and AS. CONCLUSIONS: This is the first report of real-life data on two-year survival on treatment with golimumab in RA, PsA and AS. Golimumab showed a similar retention rate when given as first or second line of treatment.

Antirheumatic drugs and reproduction in women and men with chronic arthritis.

The impact of rheumatic disease on fertility and reproduction can be remarkable. Many disease-related factors can influence patients' sexual functioning, perturb fertility and limit family planning. Antirheumatic pharmacological treatment can also have a crucial role in this field. Proper counselling, preferably provided by a multidisciplinary team of rheumatologists, obstetricians, gynaecologists and neonatologists, is recommended for patients taking antirheumatic drugs, not only at the beginning, but also during the course of treatment. Paternal exposure to antirheumatic drugs was not found to be specifically associated with congenital malformation and adverse pregnancy outcome, therefore discontinuation of these drugs while planning for conception should be weighed against the risk of disease flare. Drugs in Food and Drug Administration (FDA) category 'X' should be withdrawn in a timely manner in women who desire a pregnancy. Meanwhile, disease control can be achieved with anti-tumour necrosis factor (TNF)-α agents, which are not teratogenic drugs. If maternal disease control is permissive, they can be stopped as soon as the pregnancy test turns positive and be resumed during pregnancy in case of a flare.

Prospectively-followed pregnancies in patients with inflammatory arthritis taking biological drugs: an Italian multicentre study.

OBJECTIVES: Information on new drugs does not include their possible effects on pregnancy because pregnant women are excluded from clinical trials. Although not classified as teratogenic in animals, limited data is available on biological anti-rheumatic agents and their safety in human pregnancy. The aim of the study is to evaluate the safety of biological drugs in pregnant patients with chronic arthritis. METHODS: Pregnancy outcome and maternal disease variations were prospectively followed in six Italian Rheumatology Centres. Patients exposed to biological agents during the periconceptional period or during pregnancy were included in the study. The occurrence of congenital malformations as well as the obstetric and neonatal outcomes were assessed. RESULTS: Between 1999 and 2013 we identified 79 exposed pregnancies in 67 women affected by different rheumatic diseases with peripheral chronic arthritis. At the time of the start of pregnancy, 56 patients were taking etanercept, 13 adalimumab, 3 infliximab, 2 each certolizumab-pegol and rituximab, 1 each golimumab, anakinra and abatacept. Biological treatment was stopped after a mean of 41 days since documented pregnancy. Live births were reported in 66% of pregnancies. The rate of spontaneous pregnancy loss was 20%. Only one congenital malformation was reported. CONCLUSIONS: TNF-alpha inhibitors can be considered safe in the periconception period, representing a possible therapeutic choice also in young women affected by an aggressive form of chronic arthritis and hoping for a pregnancy. Reports of exposure during 2nd/3rd trimester are still limited and suggest caution. Experience with abatacept, tocilizumab, anakinra and rituximab in pregnancy is insufficient.

Effects of anti-TNF alpha drugs on disability in patients with rheumatoid arthritis: long-term real-life data from the Lorhen Registry.

This study involving 1033 patients with RA confirms the effectiveness of etanercept, adalimumab, and infliximab in reducing RA-related disability even in patients with a history of highly active and longstanding RA. Moreover, we found that the improvement in disability was biphasic, with a marked improvement during the first year of anti-TNF therapy, followed by slower but significant recovery over the subsequent four years.

Cardiological features in idiopathic inflammatory myopathies.

Idiopathic inflammatory myopathies (IIMs) represent a heterogeneous group of autoimmune systemic diseases characterized by chronic muscle weakness and inflammatory cell infiltrates in skeletal muscle. The most frequent IIMs, such as adult-onset polymyositis and dermatomyositis, display a wide range of clinical manifestations other than myositis, including skin changes, Raynaud's phenomenon and interstitial lung disease. Cardiac involvement is now well recognized as a clinically important manifestation in patients with polymyositis or dermatomyositis, although its actual frequency is still uncertain. Cardiovascular complications represent one of the most frequent causes of death in myositis, apart from cancer and lung involvement. Despite the fact that clinical manifestations are relatively rare, asymptomatic cardiovascular features are frequently reported in patients with polydermatomyositis and dermatomyositis. They are characterized by isolated electrocardiographic changes, valve disease, coronary vasculitis, ischemic abnormalities, heart failure and myocarditis. Chronic inflammation producing myocyte degeneration, tissues fibrosis and vascular alterations can explain the majority of reported cardiac features in myositic patients. Although previous works reported an association between heart involvement and some myositis-specific autoantibodies (namely anti-signal recognition particle), electrocardiography, echocardiography and, where necessary, heart magnetic resonance remain the mainstay for diagnosing and monitoring myocardial inflammation in these diseases. Anyway, a complete multiorgan assessment and a careful analysis of autoantibodies should be performed in every patient in order to define any possible distinct disease entities with different prognosis within the spectrum of IIMs.

Efficacy and safety of anti-tumour necrosis factor in elderly patients with rheumatoid arthritis: an observational study.

This study aims to compare the efficacy and safety of anti-TNF agents in elderly (aged >or=65 years) and younger patients (aged 18-65 years) with active RA. The study involved 1,114 RA patients treated with anti-TNF drugs and followed-up for >6 months by LORHEN group, who were divided into two cohorts on the basis of their age (311 aged >or=65 and 803 aged <65 years) in order to evaluate 3-year outcomes and treatment discontinuations. Drug effectiveness was assessed by disease activity (DAS28 and EULAR response), functional status (HAQ) and serological parameters (ESR) at baseline and during anti-TNFalpha therapy; safety was evaluated on the basis of drug discontinuation rates. At baseline, the elderly patients showed greater disease activity (DAS28, ESR) and loss of joint function (HAQ, functional class; p < 0.05). During therapy, clinical and laboratory parameters (DAS28, ESR) improved in both groups without any statistically significant difference between them, whereas the difference in HAQ remained after 36 months of treatment (p < 0.05). Anti-TNFalpha therapy was discontinued by 123 of the elderly (42%) and 282 of the younger patients (36.6%) because of loss of efficacy (17.4% vs. 16.7%), severe adverse events (21.8% vs. 16.9%) or other reasons (2.7% vs. 3%). The number of adverse events was significantly higher in the elderly patients (p < 0.05). Anti-TNFalpha treatment reduced disease activity and led to functional improvement in both groups, although the baseline difference in HAQ remained statistically significant at the end of the follow-up. The elderly patients experienced more infective events.

Tumour necrosis factor antagonist therapy and cancer development: analysis of the LORHEN registry.

OBJECTIVE: The objective was to compare cancer risk in a RA cohort population treated with TNF antagonists, and identify the characteristics of the patients at higher risk. METHODS: The study involved 1114 RA patients treated with anti-TNF agents after failing to respond to traditional DMARDs, 1064 of whom were evaluable for adverse events over an average observational period of 23.32 months. The relative cancer risks (expressed as hazard ratios) in the anti-TNF treated patients were estimated using univariate and multivariate analyses. The rate of cancer in this cohort was compared with that in the general population using data from the Varese and Milan Cancer Report. RESULTS: There were 18 incident cases (1.7%), 4 of which involved lymphomas. Comparison with the general population showed that the overall cancer risk was similar, but the risk of lymphoma was about five times higher in the RA patients treated with a biological agent. Higher RR were found in males (HR 4.95, 95% CI 1.97-12.48; p=0.001) and patients aged >65 years (HR 2.72, 95% CI 1.08-6.84; p=0.034); combined therapy with methotrexate seemed to be protective (HR 0.31, 95% CI 0.11-0.87; p=0.026). CONCLUSION: The overall cancer risk in RA patients treated with anti-TNF seemed to be similar to that in the general population in the same geographical area, but the risk of haematological cancer was significantly greater. The demographic and clinical factors associated with a higher risk of cancer in our cohort were male gender and an age of >65 years.

TNF-alpha antagonist survival rate in a cohort of rheumatoid arthritis patients observed under conditions of standard clinical practice.

A cohort of rheumatoid arthritis (RA) patients in the Lombardy Rheumatology Network (LOHREN) registry and receiving anti-TNF therapy was evaluated after 6, 12, 24, and 36 months. Of the 1114 patients in the registry 1064 met the clinical criteria for inclusion with 519 receiving infliximab, 303 adalimumab, and 242 etanercept. The therapeutic survival curve of these patients showed that the likelihood of continuing anti-TNF therapy was 78.8% after 12 months, 65.2% after 24 months, and 52.9% after 36 months, with a risk of dropout similar for inefficacy and adverse events. There were 405 anti-TNF therapy discontinuations (38.1%): 180 (16.9%) due to inefficacy, 194 (18.2%) adverse events, and 31 (2.9%) other reasons. Four deaths (2 septicemia, 1 postinfective cerebritis, 1 heart failure) were considered to be related to anti-TNF therapy. Of the discontinuations, 219 (54.1%) occurred within the first 12 months: 110 due to adverse events, 89 inefficacy, and 20 due to other reasons. After 36 months, the likelihood of survival on etanercept (62.5%) was significantly greater than the likelihood of survival on infliximab (49.1%) or adalimumab (53.6%). A higher risk of therapy discontinuations due to adverse events was associated with increasing age, a corticosteroid > 5 mg/day, a high erythrocyte sedimentation rate (ESR), a higher risk of therapy discontinuations due to inefficacy was associated with the previous use of > or = 4 disease-modifying antirheumatic drugs (DMARDs) and a high ESR. Comorbidities, increasing DAS28 values and co-therapy with methotrexate were associated with a lower risk of discontinuation.

Use of tumor necrosis factor-alpha-blocking agents in hepatitis B virus-positive patients: reports of 3 cases and review of the literature.

OBJECTIVE: To evaluate the development of hepatitis B virus (HBV) infection in patients receiving tumor necrosis factor-alpha-blocking agents (TNFBA), and to evaluate whether lamivudine (LAM) prophylaxis can reduce the risk of viral reactivation in inactive HBsAg carriers. METHODS: Local experience and published reports were reviewed. Patients with HBV infection were classified as having chronic HBV hepatitis, or being inactive HBsAg carriers or occult carriers. RESULTS: Three patients in our series and 24 patients in the literature were identified: 2 had active HBV-associated disease, 23 were inactive HBsAg carriers, and 2 occult carriers. When exposed to TNFBA, HBsAg-inactive carriers pretreated with LAM had lower risk of having detectable HBV-DNA (p=0.02) or viral reactivation (p=0.046) than those without LAM prophylaxis. In 3 patients who discontinued TNFBA, LAM prophylaxis was also discontinued 10-12 months thereafter without hepatitis flares. Two cases of reactivation in occult carriers (HBsAg-negative, anti-HBs+, anti-HBc+) were described in the literature. CONCLUSION: TNFBA should be avoided in patients with active HBV replication and should be used with caution in inactive HBsAg carriers. In these patients, the risk of viral reactivation seems to be high, but it might be reduced by prophylactic LAM, which should probably be given for a long time when TNFBA are discontinued (e.g., 12 mo). Potential occult carriers might carry a low, but not negligible, risk of viral reactivation. They should therefore be monitored with particular care.

Predicting response to anti-TNF treatment in rheumatoid arthritis patients.

OBJECTIVE: To identify the clinical factors predicting failure or a good clinical response in the cohort of RA patients entered in the Lombardy Rheumatology Network (LORHEN) registry after 3 years of treatment with anti-TNF agents. METHODS: We studied the patients who had received anti-TNF agents and been followed up for a minimum of 6 months. Disease activity at baseline and after 6 months was assessed using the DAS28, and response was evaluated according to the EULAR improvement criteria. RESULTS: 1005 patients (55.72 years) were included in the analysis. at baseline the DAS-28 was 5.91+/-0.95 and a HAQ score was 1.46+/-0.61. At mean of 14.57 months, 29.9% of the patients achieved a DAS-28 of 3 DMARDs (AHR 0.077, 95% CI 0.58-1.03; p: 0.074), a high ESR (AHR 0.86, 95% CI 0.81-0.92; p: 0.000), Steinbrocker's functional class III/IV (AHR 0.66, 95% CI 0.48-0.90; p: 0.010), a high TJC (AHR 0.97, 95% CI 0.94-0.99; p: 0.011). A 12-month EULAR non-response was observed in 153/821 (18.6%) associated with a higher baseline HAQ score (AOR 1.51, 95% CI 1.03-2.20, p: 0.033), prior treatment with >3 DMARDs (AOR 1.76, 95% CI 1.09-2.85; p: 0.021) and corticosteroid >5 mg/day (AOR 2.05, 95% CI 1.06-3.97; p: 0.034). CONCLUSION: We found that only a minority of patients with long-standing RA treated with anti-TNF agents achieve a good clinical response or remission.

Anti-TNFalpha therapy in a cohort of rheumatoid arthritis patients: clinical outcomes.

OBJECTIVE: To assess the effectiveness of anti-TNFalpha agents by analysing the principal clinical outcomes in patients with active rheumatoid arthritis (RA). METHODS: 1010 patients who received no clinical benefit from previous treatment with methotrexate and/or other DMARDs, were subsequently treated with one or more of the anti-TNFalpha agents. RESULTS: After the first six months of anti-TNFalpha therapy, 29% of the patients showed a good and 47% a moderate European League Against Rheumatism (EULAR) response, and this positive result was maintained after two years of follow-up. Their median Disease Activity Score based on the erythrocyte sedimentation rate and the evaluation of 28 joints (DAS28) decreased from 5.94 at baseline to 4 after six months (p<0.001; Delta 1.94), and further significant responses were also observed after 12, 18 and 24 months; their median 36-month DAS28 score reflected mild disease activity. The median Health Assessment Questionnaire (HAQ) score fell from 1.34 at baseline to 1 after six months of therapy (Delta 0.34; p<0.05), and a further significant reduction was observed during the second and third year of follow up. CONCLUSIONS: Especially when combined with DMARDs, anti-TNFalpha drugs can induce a good clinical response regardless of the particular molecule used, whereas their combination with steroids does not seem to improve disease outcomes at any time during follow-up.

Treatment of rheumatic diseases in patients with HCV and HIV infection.

A wide variety of rheumatic diseases has been documented in the presence of hepatitis C virus (HCV) infection and in human immunodeficiency virus (HIV) infection. In this conditions, physicians are refrained from using corticosteroids and/or immunosuppressants agents because of the risk of favouring viral replication and the progression of the underlying viral disease. In the present review we have focused our attention on the possible role of cyclosporine A (CsA), anti-Tumour Necrosis Factor (TNF) alpha agents in the treatment of HIV or HCV infected autoimmune patients. The results drown from the literature and from our personal experience confirm the safety of CsA and anti-TNF alpha agents, in terms of viral load and liver toxicity. A limited experience also suggest that both therapies can be given in combination in rheumatoid arthritis patients without increasing the risk of adverse events.