Switching from infliximab to once-weekly administration of 50 mg etanercept in resistant or intolerant patients with ankylosing spondylitis: results of a fifty-four-week study.
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Adult↗
Biomedical subjects
Fabrizio Cantini
Publications and source records attributed to Fabrizio Cantini.
New approaches in the treatment of Adamantiades-Behçet's disease.
PURPOSE OF REVIEW: To update clinicians on the recent advances in the treatment of Adamantiades-Behçet's disease. RECENT FINDINGS: Interferon-alpha-2a and infliximab have proved able to induce prompt remission in the vast majority of Adamantiades-Behçet's patients with DMARD-resistant uveoretinitis. Efficacy of interferon-alpha-2a has also been reported for mucocutaneous lesions, arthritis, and (more anecdotally) for neuro-Behçet, while results from small case series suggest that infliximab is beneficial for mucocutaneous lesions and (more anecdotally) for arthritis and gastro-intestinal manifestations. Two cases of neuro-Behçet treated with infliximab showed a complete resolution. Finally, in a randomized controlled trial of patients with mucocutaneous, arthritic manifestations, or both, etanercept effectively suppressed mucocutaneous lesions.A different approach is tolerization by oral administration of the 336-351 peptide of the human heat shock protein 60 (thought to have a pathogenic role in Adamantiades-Behçet's disease-associated uveitis), linked to recombinant cholera B-toxin B-subunit. Preliminary results have shown that tolerization is safe and effective in preventing relapses of uveitis. SUMMARY: Biologic agents have proved effective in patients resistant to conventional treatment. However, disease subsets characterized by severe morbidity and mortality such as vasculo-Behçet and neuro-Behçet still pose major therapeutic challenges. Further studies are needed to devise better treatment strategies for severe Adamantiades-Behçet's disease.
Antibodies, Monoclonal↗
Relationship between interleukin 6 promoter polymorphism at position -174, IL-6 serum levels, and the risk of relapse/recurrence in polymyalgia rheumatica.
OBJECTIVE: To assess the role of -174 G/C promoter polymorphism of interleukin 6 (IL-6) in the susceptibility to polymyalgia rheumatica (PMR). We also investigated whether this polymorphism modulates the circulating level of IL-6 and the risk of relapse/recurrence in a series of patients with PMR followed up prospectively. METHODS: A prospective study of 112 consecutive, untreated patients with isolated PMR (i.e., without evidence of giant cell arteritis) who were followed up for at least 24 months. This cohort represented all patients diagnosed over a 5-year period in one Italian rheumatological secondary referral center. Patients were monitored for clinical signs/symptoms and acute-phase reactants. All PMR patients and 112 population-based controls from the same geographic area were genotyped for IL-6 polymorphism at position -174 by molecular methods. IL-6 serum levels were measured in 67 PMR patients and 43 population-based controls. RESULTS: The distribution of the G/C 174 genotype was similar in PMR patients and controls. No significant associations with IL-6 promoter polymorphism at position -174 were found when PMR patients with and without relapse/recurrence were compared. Controls homozygous for the C allele had higher serum IL-6 levels than the carriers of the G allele (4.5 +/- 3.7 pg/ml vs 1.8 +/- 2.1 pg/ml, p = 0.01). Patients homozygous for the allele C had significantly higher values of IL-6 during followup than patients carrying GC or GG genotypes. CC homozygosity was significantly more frequent in patients with persistently elevated levels of IL-6 than in those without. The presence of persistently elevated IL-6 levels, but not the CC genotype, was associated with an increased frequency of relapse/recurrence. CONCLUSION: Our findings show that the 174 G/C promoter IL-6 polymorphism is not implicated in susceptibility to PMR. However, CC genotype characterized PMR patients with persistently elevated levels of IL-6 who are at higher risk of developing relapse/recurrence. A genetically modulated pattern of IL-6 production could affect the longterm outcome of patients with PMR.
Aged↗
Risk factors for visual loss in an Italian population-based cohort of patients with giant cell arteritis.
OBJECTIVE: To evaluate the frequency of visual manifestations at presentation in an Italian population-based cohort of patients with biopsy-proven giant cell arteritis (GCA), and to investigate predictors for the development of permanent visual loss. METHODS: We identified 136 Reggio Emilia (Italy) residents with biopsy-proven GCA diagnosed between 1986 and 2002. Medical records of these 136 patients were reviewed, and demographic, clinical, and laboratory data were collected.Multivariate analysis with multiple logistic regression models was performed to identify the best predictors of visual loss. RESULTS: Visual manifestations developed in 41 patients (30.1%). Partial or total visual loss was observed in 26 patients (19.1%). Anterior ischemic optic neuropathy was seen in 24 patients, and 2 patients had central retinal artery occlusion. Unilateral vision loss occurred in 19 patients, and bilateral visual loss in 7. In 25 patients, visual loss developed before glucocorticoid therapy for GCA was started. The age at disease onset was significantly higher in patients with permanent visual loss compared with those without it. The frequency of systemic signs/symptoms and erythrocyte sedimentation rate (ESR) and C-reactive protein values at diagnosis were significantly lower in patients with permanent visual loss. By multivariate logistic regression, the only statistically significant predictor for the development of permanent visual loss was the absence of high levels of ESR at diagnosis (tertile 2: Odds ratio [OR] 0.08; tertile 3: OR 0.11). Other predictors included in the model were the absence of systemic manifestations (OR 0.24), an older age at disease diagnosis (quintile 5: OR 5.60), and the presence of an elevated platelet count at diagnosis (OR 4.99), however they were only of borderline statistical significance. CONCLUSION: The proportion of Italian patients with GCA that developed visual loss was similar to that reported from other countries. The patients with low inflammatory response had a higher risk of visual loss.
Age of Onset↗
Acute-phase reactants and the risk of relapse/recurrence in polymyalgia rheumatica: a prospective followup study.
OBJECTIVE: To determine laboratory parameters that may be useful in identifying polymyalgia rheumatica (PMR) patients who require long-term corticosteroid therapy. METHODS: A prospective followup study of 94 consecutive untreated patients with PMR were assessed for relapse/recurrence for a mean of 39 months. This cohort represented all the patients diagnosed over a 4-year period in 2 Italian secondary referral centers. Patients were monitored for clinical signs and symptoms, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and serum interleukin-6 (IL-6). IL-6 levels were also measured in 43 controls matched to the patients for age and sex. RESULTS: The ESR was elevated in 91.5% of the patients prior to therapy initiation, as were CRP in 98.9% and serum IL-6 in 92.6%. Forty-seven (50.0%) patients had at least 1 relapse/recurrence during the followup period and 24 (25.5%) had at least 2. After 4 weeks of prednisone therapy, ESR was elevated in 13.2% patients, CRP in 41.9%, and serum IL-6 in 37.2%. IL-6 levels remained persistently elevated in 9.9% and CRP in 8.7% of patients during the first year of followup, whereas no patient had persistently elevated ESR. Persistently elevated CRP and IL-6 levels were significantly associated with an increased risk of relapse/recurrence. In particular, patients with persistently elevated levels of IL-6 during the first year of therapy had the highest relative risk. CONCLUSION: Despite the control of clinical symptoms, corticosteroids do not adequately control the inflammatory process in a subset of patients with PMR who have persistently elevated levels of CRP and IL-6 and who have a higher risk of relapsing.
Acute-Phase Proteins↗
Factor V Leiden and prothrombin gene G20210A mutations in Italian patients with Behçet's disease and deep vein thrombosis.
OBJECTIVE: To evaluate the frequency and type of vascular lesions and to study the association of factor V gene G1691A (Leiden) and prothrombin gene G20210A polymorphisms with venous thrombosis in Italian patients with Behçet's disease (BD). METHODS: Included were 118 consecutive Italian BD patients followed over a 3-year period (1997-1999) who satisfied the International Study Group criteria for BD. The control group consisted of 132 healthy Italian blood donors. All BD patients and controls were genotyped by polymerase chain reaction and allele-specific restriction enzyme techniques for factor V Leiden and prothrombin gene G20210A polymorphisms. RESULTS: Vascular lesions were observed in 37 (31.4%) patients. The 2 most common lesions were subcutaneous thrombophlebitis (10.2%) and deep vein thrombosis (DVT) of the legs (22.8%). No significant demographic and clinical differences between patients with and without DVT were present. The distribution of allele and genotype frequencies of prothrombin gene G20210A and factor V Leiden polymorphisms did not differ significantly between BD patients and healthy controls. The frequencies of carriage rates of prothrombin gene G20210A and factor V Leiden polymorphisms in BD patients with and without DVT were similar. However, the frequency of 20210A allele was significantly higher in BD patients with ocular disease than in those without, particularly in the patients with posterior uveitis/retinal vasculitis. CONCLUSIONS: The frequency and types of vascular lesions in Italian BD patients were similar to those reported in studies from other countries. No association between factor V Leiden mutation and G20210A mutation in the 3'-untranslated region of the prothrombin gene with DVT was found. However, a prothrombin gene G20210A mutation may influence the development and severity of ocular involvement in BD.
Adolescent↗
Polymyalgia rheumatica.
Polymyalgia rheumatica (PMR) is an inflammatory condition of unknown etiology characterized by aching and stiffness in the shoulder and in the pelvic girdles and neck. In the past, PMR was considered a manifestation of giant cell arteritis (GCA) or a variant of elderly-onset rheumatoid arthritis (EORA). The current diagnostic criteria for PMR were empirically formulated by clinical experts who had studied the disease extensively. Arthroscopic, radioisotopic and magnetic resonance imaging studies all have indicated the presence of a synovitis in proximal joints and periarticular structures. The synovitis is probably responsible for the musculoskeletal symptoms in PMR. The prominence assigned to the proximal symptoms has probably overshadowed the less well recognized and more variable distal musculoskeletal manifestations which are present in about half of the cases. A normal erythrocyte sedimentation rate does not exclude a diagnosis of PMR. C-reactive protein and interleukin-6 seem to be more sensitive indicators of disease activity both at diagnosis and during relapse/recurrence. Corticosteroids are the drugs of choice for treating PMR. A course of treatment of 1-2 years is often required. However, some patients have a chronic, relapsing course and require low doses of corticosteroids for several years. Large, multicenter, double-blind, placebo-controlled studies are required to define the role of methotrexate and anti-TNF-alpha agents as corticosteroid-sparing drugs in PMR.
Aged↗
Are polymyalgia rheumatica and giant cell arteritis the same disease?
OBJECTIVE: To summarize the evidence about the relationship between polymyalgia rheumatica (PMR) and giant cell arteritis (GCA). METHODS: Review of relevant articles from the English-language literature. RESULTS: Epidemiologic studies suggest that PMR and GCA are closely related conditions affecting people over 50 years and frequently occurring in the same patient. PMR symptoms have been observed in 40 to 60 percent of GCA clinical series. Also, temporal artery biopsy may yield positive results for GCA in patients with isolated PMR. Conflicting HLA-DRB1 genotype results have been reported, and recent studies have shown that PMR and GCA have different expression of RANTES, TNFalpha microsatellite, and IL-6 promoter genetic polymorphisms. Search for a possible common infectious agent have yielded disappointing results. Although parvovirus B19 DNA is present in the artery wall of patients with GCA, this virus may be only an innocent bystander. Cytokine studies on a limited number of temporal artery biopsy specimens have shown that interferon-gamma is produced in GCA and not in PMR, suggesting that this cytokine may be crucial to the development of overt vasculitis. CONCLUSIONS: PMR and GCA frequently occur together but no definitive conclusions can be drawn about the nature of this association.
Aged↗
Fat suppression magnetic resonance imaging in shoulders of patients with polymyalgia rheumatica.
OBJECTIVE: To evaluate the sites of inflammatory process in the shoulders of patients with polymyalgia rheumatica (PMR) using fat suppressed magnetic resonance imaging (MRI). METHODS: Six consecutive, untreated new patients with PMR were investigated. Five patients with early rheumatoid arthritis (RA) and 4 patients with early psoriatic arthritis (PsA) with bilateral shoulder symptoms served as a control group. Bilateral shoulder fat-suppressed MRI sequences were performed in all patients and controls. We evaluated the presence of joint synovitis, bursitis, tenosynovitis, and bone and soft tissue edema. RESULTS: Bilateral subacromial/subdeltoid bursitis was found in all patients with PMR, in 1/5 (20%) patients with RA (p < 0.05), and in none with PsA (p < 0.02). Glenohumeral synovitis was present in all case and controls. Biceps tenosynovitis was observed in 4/6 (67%) patients with PMR, in 4/5 (80%) with RA (not significant, NS), and in all 4 patients with PsA (NS). No evidence of bone edema adjacent to the joint capsule and entheseal insertions or in the soft tissues was present in either cases or controls. CONCLUSION: The absence of extracapsular abnormalities in the early shoulder disease of PMR does not confirm the hypothesis of a capsular-based disorder.
Aged↗
Vascular endothelial growth factor gene polymorphisms in Behçet's disease.
OBJECTIVE: To evaluate potential associations of vascular endothelial growth factor (VEGF) gene polymorphisms with Behçet's disease (BD) and disease expression. METHODS: Case patients were 122 consecutive Italian patients with BD followed at the Rheumatology, Ophthalmology, and Neurology Units in Bologna, Ferrara, Milano, Palermo, Potenza, Prato, Reggio Emilia, and Trento over a 3-year period (1997-99) and who satisfied the International Study Group criteria for BD. Also selected as a control group were 200 healthy age and sex matched blood donors. All patients with BD and controls were genotyped by polymerase chain reaction and allele-specific oligonucleotide techniques for +936 C/T (rs3025039) and -634 C/G (rs2010963) mutations and for an 18 base pair (bp) insertion/deletion (I/D) polymorphism at -2549 of the the VEGF promoter region. In vitro release of VEGF by peripheral blood mononuclear cells (PBMC) was investigated by ELISA in healthy controls homozygous for the polymorphisms studied. RESULTS: The carriage rates of the alleles I and -634C were significantly more frequent in patients with BD than in healthy controls [p corr = 0.036, OR 1.8 (95% CI 1.1-2.9) and p corr = 0.05, OR 1.8 (95% CI 1.1-3.0), respectively]. While the distribution of allele +936T was similar in patients with BD and healthy controls, its frequency was significantly higher in BD patients with posterior uveitis/retinal vasculitis than in those without (p = 0.022, OR 2.4, 95% CI 1.1-5.0). Lipopolysaccharide-stimulated VEGF production from PBMC of healthy subjects was higher in II homozygous than in DD homozygous. CONCLUSION: Our data indicate that carriers of -634C and I alleles are associated with susceptibility to developing BD.
Adolescent↗
Efficacy of infliximab in resistant psoriatic arthritis.
OBJECTIVE: To evaluate the efficacy and safety of the anti-tumor necrosis factor alpha monoclonal antibody infliximab in the treatment of active psoriatic arthritis (PsA) resistant to previous symptom modifying antirheumatic drugs. METHODS: Sixteen patients with peripheral active PsA with at least 6 months of methotrexate (MTX) therapy at a stable dosage were treated with infliximab administered at a dosage of 3 mg/kg at 0, 2, 6, 14, 22, and 30 weeks while continuing to receive MTX. Intake of nonsteroidal antiinflammatory drugs and corticosteroids was stable during the study period. Standard clinical assessments, erythrocyte sedimentation rate (ESR), and C reactive protein (CRP) were determined at baseline and at weeks 2, 6, 14, 22, and 30. RESULTS: By week 2, significant improvements were registered in the number of swollen and tender joints, visual analog scale for pain, patient and doctor global disease assessment scores, Health Assessment Questionnaire, Dougados functional index, ESR, and CRP. At week 30, the percentages of patients satisfying American College of Rheumatology (ACR) 20%, ACR 50%, and ACR 70% response rates were 64%, 57%, and 57%, respectively. In the 3 patients with active axial disease, spinal stiffness and pain resolved almost completely at week 2 and the improvement did not diminish over time. Psoriasis Area Severity Index improvement was 37% at week 2 and 86% at week 30. No patients dropped out for treatment failure. Side effects were observed in 4 of 16 patients, 2 of whom suspended the therapy due to a severe allergic reaction. CONCLUSION: In patients with resistant PsA, infliximab is an effective therapy without major side effects.
Adult↗
Persistent efficacy of tumor necrosis factor alpha blockage therapy in SAPHO syndrome: comment on the article by Wagner et al.
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Acquired Hyperostosis Syndrome↗
Disease activity and antinucleosome antibodies in systemic lupus erythematosus.
OBJECTIVE: To evaluate the correlation between antinucleosome antibodies and disease activity in patients with systemic lupus erythematosus (SLE). METHODS: We evaluated antinucleosome antibodies (by ELISA) in 48 SLE patients. They were divided in 2 groups: positive (Group A, nr = 18) and negative (Group B, nr=30). The groups were evaluated for antinucleosome antibodies and for clinical, humoral parameters (hemoglobin, blood cell count, urinanalysis, ESR, ANA, anti-dsDNA, anticardiolipin antibodies, LAC), and ECLAM. RESULTS: C3,C4, and hemoglobin were lower in Group A than (vs) group B (C3: 0.61 +/- 0.16 g/L vs 0.88 +/- 0.08 g/L, p < 0.001; C4: 0.086 +/- 0.03 g/L vs 0.18 +/- 0.07 g/L, p < 0.05; hemoglobin: 8.7 +/- 5.8 g/dL vs 12.7 +/- 1.44 g/dL; p < 0.02). ECLAM was higher in group A 7.56 +/- 2.19 vs group B 4.67 +/- 1.35 (p < 0.001). Urinary sediment was more altered in group A (88.8%) vs group B (33.3%; p < 0.001). CONCLUSION: We found a correlation between antinucleosome antibodies and SLE disease activity as expressed by the higher ECLAM score in group A.
Adult↗
Treatment of refractory polymyalgia rheumatica with infliximab: a pilot study.
OBJECTIVE: To investigate whether infliximab has a steroid-sparing effect in the treatment of patients with polymyalgia rheumatica (PMR) who are resistant to corticosteroid (CS) therapy and have had CS-related side effects. METHODS: In a pilot study, infliximab 3 mg/kg was administered at weeks 0, 2, and 6 in 4 patients with relapsing PMR who were not able to reduce their prednisone dose below 7.5-12.5 mg/day and who had experienced multiple vertebral fractures. The patients were regularly monitored for clinical signs/symptoms and erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and interleukin-6 (IL-6) during the one-year followup period. RESULTS: Two patients had a complete response to infliximab with clinical remission 2 weeks after the first infusion. At this time ESR and IL-6 values were normal and the patients were able to suspend prednisone. Normal ESR, CRP, and IL-6 levels persisted after the suspension of infliximab and prednisone during the followup period, paralleling the clinical remission. The third patient had a complete and persistent clinical remission 2 weeks after the first infusion, although IL-6 levels remained elevated during the followup period despite the normalization of ESR values. These 3 patients were symptom-free with normal ESR and CRP at the end of 1-year of followup. The fourth patient had continuous clinical activity associated with persistently elevated acute phase reactants, although IL-6 levels measured during followup were lower compared to baseline values and the patient was able to reduce prednisone dosage to 5 mg/day. CONCLUSION: Our encouraging results suggest that a controlled study may assess the efficacy of infliximab as CS-sparing drug in PMR.
Antibodies, Monoclonal↗
Is duplex ultrasonography useful for the diagnosis of giant-cell arteritis?.
BACKGROUND: Evidence of a dark halo on ultrasonography has been considered a specific sign of giant-cell arteritis and may replace temporal artery biopsy for the diagnosis of giant-cell arteritis in patients with typical clinical manifestations. OBJECTIVE: To assess the usefulness of temporal artery duplex ultrasonography and to compare this mode of ultrasonography with physical examination of temporal arteries for the diagnosis of giant-cell arteritis in patients with suspected giant-cell arteritis or polymyalgia rheumatica. DESIGN: Diagnostic test study. SETTING: Several divisions of Reggio Emilia Hospital, Reggio Emilia, Italy. PATIENTS: 86 consecutive patients with a suspected diagnosis of giant-cell arteritis or polymyalgia rheumatica identified over a 22-month period. MEASUREMENTS: The temporal arteries were examined in all 86 patients. Duplex ultrasonography of the temporal arteries was then performed by two ultrasonographers who were unaware of the clinical diagnosis. Before corticosteroid therapy was started, temporal artery biopsies were performed in all patients at the site targeted by the ultrasonographer. RESULTS: A hypoechoic halo around the lumen of the temporal arteries had a sensitivity of only 40% (95% CI, 16% to 68%) and a specificity of 79% (CI, 68% to 88%) for the diagnosis of biopsy-proven giant-cell arteritis. The negative likelihood ratio was 0.8 (CI, 0.5 to 1.2), and the positive likelihood ratio was 1.9 (CI, 0.9 to 4.1). When the thickness of the halo was at least 1 mm, specificity increased to 93% (CI, 84% to 98%) and the positive likelihood ratio increased to 5.7 (CI, 2.0 to 16.2); however, sensitivity remained low at 40% (CI, 16% to 68%). On physical examination, temporal artery abnormalities had a higher sensitivity of 67% (CI, 38% to 88%), a higher specificity of 99% (CI, 92% to 100%), and a higher positive likelihood ratio of 47.3 (CI, 6.5 to 342.4) than did ultrasonographic findings. None of the patients with giant-cell arteritis had a normal temporal artery inspection and a hypoechoic halo on ultrasonography. CONCLUSION: Evidence on ultrasonography of a halo around temporal arteries, either any halo or a halo 1 mm or greater in thickness, only modestly increased the probability of biopsy-proven giant-cell arteritis but did not improve the diagnostic accuracy of a careful physical examination.
Aged↗
Polymyalgia rheumatica and giant-cell arteritis.
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Adrenal Cortex Hormones↗
Detection of parvovirus B19 DNA by polymerase chain reaction in giant cell arteritis: a case-control study.
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Aged↗
Fast spin echo-T2-weighted sequences with fat saturation in dactylitis of spondylarthritis. No evidence of entheseal involvement of the flexor digitorum tendons.
OBJECTIVE: To establish by means of fast spin echo (FSE)-T2-weighted sequences with fat saturation if enthesitis of the flexor digitorum superficialis and profundus tendons is the primary lesion in spondylarthritis (SpA) finger dactylitis. METHODS: Eleven dactylitic fingers and their corresponding normal, contralateral fingers, belonging to 6 patients who met the Amor criteria for SpA, were studied by FSE-T2-weighted sequences with fat saturation. RESULTS: All dactylitic fingers showed moderate or severe fluid collection in the flexor tendon synovial sheaths. Involvement of the joint cavity was simultaneously present in at least one joint in 3 (27.3%) of the 11 fingers. A mild to moderate peritendinous soft tissue edema was observed in 5 (45.5%) of the 11 affected fingers. In no dactylitic finger was bone edema observed near the insertions of the flexor digitorum superficialis or profundus tendons or in other sites of the phalanges. No lesions were observed in the 11 contralateral, clinically normal fingers. CONCLUSION: In SpA dactylitis there is no evidence of enthesitis of the flexor digitorum tendons and joint capsules.
Adult↗