Charalampos Papagoras

Strategies after the failure of the first anti-tumor necrosis factor α agent in rheumatoid arthritis

During the last two decades fundamental changes have taken place in the treatment of patients with rheumatoid arthritis (RA). The effective establishment of methotrexate as the anchor drug and the introduction of new drugs, in particular anti-tumor necrosis factor (TNF) alpha blockers and the novel biologics have made the goal of remission feasible for plenty of RA patients. However, almost 14-38% of patients do not respond to first-line anti-TNF-alpha treatment at all and as many as 40% discontinue these drugs within a year and 50% within 2 years. Currently, no recommendations exist as regards the treatment of RA patients after TNF-alpha-antagonist failure. In this review the issue of anti-TNF-alpha therapy failure is discussed. Further, the various options for overcoming the apparent failure are explored according to evidence from the published literature.

Sustained Clinical Response in Psoriatic Arthritis Patients Treated with Anti-TNF Agents: A 5-year Open-Label Observational Cohort Study

OBJECTIVEnTo investigate the efficacy, toxicity, and drug discontinuation in patients with psoriatic arthritis treated with anti-tumor necrosis factor agents.nnnMETHODSnSixty-five patients with active disease were included in this open-label study. They had tender or swollen joint count ≥5, Psoriatic Arthritis Severity Index (PASI) score ≥10, and erythrocyte sedimentation rate ≥28 mm Hg/1st hour and/or C-reactive protein ≥10 mg/L. All were refractory to at least 2 disease-modifying antirheumatic drugs. Thirty were treated with infliximab, 25 with etanercept, and 10 with adalimumab. Infliximab (5 mg/kg body weight) was given intravenously at weeks 0, 2, 6, and every 8 weeks thereafter; etanercept was given subcutaneously (25 mg twice a week), while adalimumab was given subcutaneously (40 mg every other week) for a period of 5 years. Data concerning anti-tumor necrosis factor efficacy tolerability, adverse events, and drug discontinuation were recorded. The percentage of patients who achieved the Psoriatic Arthritis Response Criteria (PSARC), the improvement of PASI, the improvement according to the American College of Rheumatology (ACR) criteria, and the disease activity for 28 joint indices score (DAS-28) were recorded.nnnRESULTSnAfter 5 years, PSARC was 60%, PASI 70 was 66.7%, PASI 90 was 63.3%, while ACR 50 was 56.7% for the patients treated with infliximab. Moreover, PsARC was 64%, PASI 70 and PASI 90 were 68%, while ACR 50 was 56% for those treated with etanercept. Furthermore, in the adalimumab group PsARC was 56%, PASI 70 and PASI 90 were 58% and 50%, respectively, while ACR 50 was 50%. Additionally, DAS-28 scores were significantly improved. Thirteen patients treated with infliximab, 6 with etanercept, and 5 patients with adalimumab were withdrawn. At the end of treatment, the survival of infliximab was 56.7%, for etanercept 76%, and for adalimumab 50%.nnnCONCLUSIONnAll drugs were effective, safe, and well-tolerated. The clinical improvement was maintained through the 5 years with satisfying infliximab and adalimumab survival and high etanercept survival.

Cardiovascular risk profile in patients with spondyloarthritis

OBJECTIVESnThe spondyloarthritides (SpA) are associated with an increased cardiovascular risk. We studied cardiovascular risk factors in patients with SpA.nnnMETHODSnThe following risk factors were assessed in SpA patients and healthy controls: smoking, family history of premature ischemic heart disease, obesity, serum lipids, apolipoproteins, urate and carotid intima media thickness (IMT).nnnRESULTSnOverall 150 patients (73 with ankylosing spondylitis [AS], 71 with psoriatic arthritis [PsA] and six with other SpA types) were included. Generally SpA patients were significantly more often smokers, while PsA patients had greater values of abdominal obesity. AS patients had significantly lower levels of triglyceride, HDL, ApoB, ApoE and Lp(a) and a higher atherogenic index (total cholesterol/HDL). PsA patients had significantly lower levels of HDL, ApoAI and ApoE, an elevated atherogenic index and higher serum urate. In multivariate analysis the atherogenic index was positively associated with SpA across all patient groups independently of smoking and other lipid parameters. Carotid IMT in SpA patients (0.71 mm) was higher than controls (0.63 mm, P=0.017), although after adjusting for smoking this ceased to be significant. Treatment of patients with previously untreated disease resulted in a small but significant decline in ApoB levels at 6 months (P=0.045), which, however, was no longer evident at 12 months.nnnCONCLUSIONnSpondyloarthritis patients are at a greater cardiovascular risk owing to the higher prevalence of smoking and a higher atherogenic index. PsA patients have more abdominal fat and higher urate levels. Immunosuppressive treatment of SpA produces minor and temporary effects on the lipid profile.

Fertility in male patients with seronegative spondyloarthropathies treated with infliximab

OBJECTIVESnThe majority of patients with ankylosing spondylitis (AS) and psoriatic arthritis (PsA) are affected during their peak reproductive years. Tumor necrosis factor (TNF)α plays a pivotal role in the pathogenesis of both diseases. Today, anti-TNFα blockers are an essential treatment for these patients. To identify male patients who achieved pregnancy development during their management with anti-TNFα blockers (infliximab).nnnMETHODSnWe reviewed the data of 65 patients with AS and 30 patients with PsA who were followed-up in our rheumatology outpatients clinic and they were on infliximab therapy between January 2001 and December 2010.nnnRESULTSnWe identified overall seven male patients with AS and three male patients with PsA who had fathered 14 healthy infants. Moreover, we recognized one man with PsA who was on infliximab and on concomitant therapy with MTX at the time of conception, whose wife had to proceed to therapeutic abortion due to congenital abnormalities of the fetus (hydrocephalia), while she was on the first trimester of pregnancy.nnnCONCLUSIONSnWe described male patients with AS and PsA who demonstrated no fertility problems while they were on infliximab treatment. The data designated in this report provide some supportive evidence for the safe use of infliximab in male patients who are affected of those inflammatory diseases during their peak reproductive years.

A case report of a psoriatic arthritis patient on hemodialysis treated with tumor necrosis factor blocking agent and a literature review

This report seeks to describe the clinical efficacy and safety of infliximab in a patient with psoriatic arthritis on hemodialysis and to review the literature on the topic. We present a patient with psoriatic arthritis on hemodialysis treated with infliximab and we review the literature. Our case includes a patient with severe psoriasis and dactylitis with chronic renal failure requiring regular hemodialysis. At presentation the patient had a psoriasis area and severity index (PASI) score of 35.1 and dactylitis affecting the right thumb. Evaluation of laboratory parameters revealed a slight increase of erythrocyte sedimentation rate (21xa0mm/h) and a mild normocytic anemia (Hct 36.4). The rest of the laboratory and imaging tests were within normal limits. Infliximab was initiated at the loading dose of 5xa0mg/kg body weight at weeksxa00, 2, 6, and every 8xa0weeks thereafter. On retreatment at weekxa014 the PASI score was measured to 3.4. After the conclusion of 6xa0months of treatment, the reduction of PASI score was sustained reaching the point of 0.8. In addition, dactylitis, as well as laboratory parameters, showed a striking improvement. On the other hand, during the same period of time, no changes of renal functions were noted and no complications were reported and the patient continued his hemodialysis on a regular basis. Our case is in accordance with other reports supporting that infliximab treatment in patients undergoing hemodialysis can be safe, well tolerated, and effective. However, larger trials are needed to prove its use in these patients.

Adalimumab in the treatment of rheumatoid arthritis.

Adalimumab (ADA), a fully human monoclonal antibody against TNF-α is indicated for the treatment of rheumatoid arthritis (RA), psoriatic arthritis, ankylosing spondylitis, juvenile idiopathic arthritis, Crohns disease, ulcerative colitis and psoriasis. In RA, it may be prescribed in combination with methotrexate or other disease-modifying antirheumatic drugs or as monotherapy. Studies comparing ADA with other TNF-α inhibitors are limited and are based mainly on meta-analyses of randomised controlled trials and large observational cohorts. In this study, the effectiveness and safety of ADA is compared with that of etanercept and infliximab.

Heart involvement in systemic sclerosis: a combined echocardiographic and scintigraphic study.

The aim of this study is to investigate systemic sclerosis (SSc) patients without clinically evident heart disease for cardiac abnormalities. SSc patients and age- and sex-matched healthy controls from the hospital staff underwent transthoracic echocardiography for the assessment of the left ventricle (LV) morphology and function and estimation of the pulmonary artery systolic pressure (PASP). Patients further underwent stress-rest myocardial perfusion imaging (MPI) scintigraphy by single-photon emission computed tomography (SPECT). Thirty-seven patients were included (33 women, 19 with diffuse, and 18 with limited SSc). LV hypertrophy was more common in SSc patients than controls (24.3 vs 0xa0%, pu2009=u20090.001). Impaired LV relaxation was found in 45.9xa0% of patients and 40.5xa0% controls (pu2009=u20090.639). Excluding patients with arterial hypertension, LV hypertrophy was still found in 23.1xa0% and LV relaxation impairment in 38.5xa0%. PASP over 30xa0mmHg was found in 13 patients (35.1xa0%), 11 of whom had no history of pulmonary arterial hypertension (PAH). Of 35 patients who underwent SPECT, 21 patients (60xa0%) exhibited reversible LV perfusion defects. Their mean age was 51.8xa0years; four patients were younger than 40xa0years old and eight patients younger than 50xa0years. In all cases, ischemia was graded as mild or moderate and in a single case, graded as significant. Subclinical heart involvement is common in SSc patients even in the younger age groups. LV hypertrophy and impaired relaxation, raised PASP, and ischemia on MPI with SPECT are found in a significant proportion of SSc patients. Careful screening of SSc patients for potential heart involvement and consultation by a cardiologist may be of value.

Periocular xanthogranuloma: A forgotten entity?

Periocular xanthogranulomatous diseases are a rare group of disorders which are characterized by a predilection to affect the orbit and ocular adnexa and special histopathological features, in particular infiltrates comprising non-Langerhans-derived foamy histiocytes and Touton giant cells. The differential diagnosis is difficult and occasionally definite diagnosis cannot be established even after clinical and histopathological findings are taken together. We describe a case of a middle-aged man who presented with a 10-year history of voluminous eyelid swelling with concomitant late-onset atopic manifestations, namely bronchial asthma and allergic rhinitis with nasal polyps. After thorough clinical and laboratory investigation, including a biopsy of the eyelid, we classified the patient’s disease to a rare entity that has been relatively recently described: periocular xanthogranuloma associated with adult-onset asthma. In a review of the literature, no prospective trials concerning the treatment of this disease were found. The literature mainly contained case reports and case series in which corticosteroids and chemotherapy with alkylating agents have been reported to be beneficial. We treated our patient with a combination of oral corticosteroids and cyclophosphamide pulses and we observed substantial regression of the eyelid masses together with a normalization of systemic immunologic abnormalities.

Abatacept: a biologic immune modulator for rheumatoid arthritis

Introduction: Abatacept is a biologic drug that belongs to the class of T-cell co-stimulation modulators and is used for the treatment of rheumatoid arthritis (RA). Areas covered: This article covers major randomized clinical trials and meta-analyses concerning abatacept in the treatment of RA, as identified in a Pubmed search. Scientific meeting abstracts describing long-term extension data of the identified trials are also included. Efficacy outcomes and the safety profile are the focus of this evaluation. Expert opinion: Abatacept in combination with methotrexate (MTX) or other synthetic disease-modifying anti-rheumatic drugs (DMARD) has been proven effective for the treatment of RA in different groups of patients: with early RA and no prior exposure to DMARD; with DMARD-resistant RA; and with RA not responding to TNF-α-blocking agents. Significant reductions of disease activity are achieved, with 1-year remission rates reaching up to 41% of DMARD-naïve patients with early RA receiving a combination of abatacept plus MTX. Abatacept treatment has been shown to improve function and quality of life and to suppress radiographic progression. No major safety issues have emerged during clinical trials and long-term extensions. Therefore, abatacept is a drug with a favorable efficacy and safety profile, which may offer substantial benefits to RA patients.

Long-term use of adalimumab in the treatment of rheumatic diseases

Adalimumab, a fully humanized monoclonal antibody against tumor necrosis factor-alpha (TNFα), has been evaluated in various randomized placebo-controlled trials in rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis and juvenile idiopathic arthritis. In the short time frame of these trials adalimumab has been shown to be effective in reducing disease activity, slowing radiographic disease progression and improving patients’ quality of life, while at the same time demonstrating an acceptable safety profile. Furthermore, release of adalimumab on the market, prospective observational studies, as well as open-label extensions of the original double-blind trials have provided experience and data about the long-term efficacy and safety of the drug. Initial effectiveness, in terms of reducing disease activity, is sustained, while in most cases patients treated with adalimumab experienced a slower radiographic progression and consequently less disability and improved health-related quality-of-life outcomes. Moreover, long-standing treatment of thousands of patients with adalimumab outside the controlled context of clinical trials was not related to new safety signals, with the most common adverse events being respiratory infections. The most common serious adverse events seem to be tuberculosis reactivation, while a putative association with malignant lymphoma development is not yet proven. Besides, both of these adverse reactions pertain to the whole TNFα blocker group. In conclusion, adalimumab is a safe and effective option for the treatment of patients with rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis and juvenile idiopathic arthritis.