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ABSTRACT: Adolescents with juvenile idiopathic arthritis (JIA) are transferred from paediatrics to adult-oriented healthcare when they reach early adulthood. Research on the extent to which patients' expectations about the adult healthcare setting match their actual experience after transfer, may promote successful transfer from paediatrics to adult care. As part of the 'Don't Retard' project ( http://www.kuleuven.be/switch2/rheuma.html ), experiences and expectations of young adults regarding their transfer from paediatric rheumatology to adult rheumatology were explored. A qualitative study was conducted using semi-structured, in-depth interviews of 11 patients with JIA, aged 18 to 30. Data were analysed using procedures inherent to the content analysis approach. For both concepts, experiences and expectations, three main themes emerged: 'preparation', 'parental involvement' and an 'adapted setting for the late-adolescent or early adult'. The need for a gradual process covered the themes 'preparation' and 'parental involvement'. Young people with JIA prefer to have a say in the moment of transfer and in the reduction of parental involvement. The majority of the participants like their parents' presence at the first consultation at the adult rheumatology department. They expect a healthcare setting adapted to their needs and the possibility to meet peers in this setting. Sudden confrontation with older patients with severe rheumatoid arthritis at adult rheumatology was an unsettling experience for some of the young patients and they declared that better preparation is needed. This study enabled us to define three main themes important in transfer. These themes can facilitate healthcare professionals in developing specific interventions to prepare the young people to transfer, to regulate parental involvement and to arrange an adapted setting for them. Since we included patients who were in follow-up at one tertiary care centre, in which both paediatric and adult rheumatology care are located, the results of the study cannot be generalised to the entire population of patients with JIA.
Clinical Rheumatology 12/2012; · 2.00 Impact Factor
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Marie Vanthuyne,
Vanessa Smith,
Ellen De Langhe,
Jens Van Praet,
Seher Arat,
Geneviève Depresseux, Rene Westhovens,
Daniel Blockmans,
Valérie Badot,
Elie Cogan,
Filip De Keyser,
Frédéric A Houssiau
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ABSTRACT: OBJECTIVE: To report baseline and followup data on the first 438 patients with systemic sclerosis (SSc) included in the Belgian Systemic Sclerosis Cohort. METHODS: According to LeRoy and Medsger's classification, 73 patients with limited SSc (lSSc), 279 with limited cutaneous SSc (lcSSc), and 86 with diffuse cutaneous SSc (dcSSc) were included. History was collected and clinical examination, blood tests, and paraclinical investigations were repeated. The Disease Activity Score (DAS) and Disease Severity Score (DSS) of several organ systems were computed. An organ system was considered to demonstrate SSc if the corresponding DSS was ≥ 1. RESULTS: At baseline, patients with dcSSc had more general, joint/tendon, muscle, gastrointestinal, and kidney involvement. Mean DLCO was below normal in patients with lSSc, indicating unsuspected lung involvement. Patients with anti-Scl-70 had more vascular, skin, joint/tendon, and lung involvement. Patients with anti-RNA polymerase III had more skin and joint/tendon involvement compared to patients with anticentromere. Time to death was statistically shorter for patients with dcSSc. New-onset lung disease was the most common complication over time. No changes in DAS were observed. By contrast, the general and the skin DSS worsened in patients with lcSSc and lSSc, respectively. Fifteen percent of patients with lSSc shifted to lcSSc at Month 30, but neither serology nor capillaroscopy findings at baseline were helpful in identifying those at risk. CONCLUSION: Our data indicate that the DSS can be used to define organ involvement in SSc. Differences can be seen between subsets classified not only according to cutaneous subtypes but also to autoantibody profile.
The Journal of Rheumatology 09/2012; · 3.69 Impact Factor
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Nature Reviews Rheumatology 07/2012; 8(8):445-7. · 8.39 Impact Factor
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ABSTRACT: To determine the prevalence of RA and its distribution among linguistic groups in the urban area of Kinshasa.
Investigators questioned all individuals living in randomly chosen streets in five randomly chosen health areas in Kinshasa. Age, sex, linguistic group and rheumatic complaints were noted. RA diagnosis by 1987 ACR classification criteria was checked in all suspect cases. Disease activity (DAS-28), functionality (HAQ), X-ray damage, ACPA and RF positivity were assessed in patients confirmed with RA.
A total of 5000 individuals were questioned, with 2700 females and 2300 males [average age 25.7 (1.8) years]. Linguistic group definitions were obtained in 4587 subjects: 44.3% had Kongo roots, 16.9% Ngala, 16.7% Luba, 11% Swahili, 3.6% Tetela and 7.6% miscellaneous. Thirty persons (age ± 53 years) fulfilled the ACR criteria with a female/male sex ratio of 5. Mean age at disease onset was 47.7 years. Kongo people had the highest RA prevalence (1%). Mean DAS-28 was 6.5, mean HAQ was 1.3. One-third of patients were RF and ACPA positive and had classical X-ray findings.
The prevalence of RA in Kinshasa is 0.6 and 0.9% in people aged >18 years. Disease activity was high, but RF and ACPA positivity was not frequent. The Kongo seems to be the most affected linguistic group.
Rheumatology (Oxford, England) 05/2012; 51(9):1644-7. · 4.24 Impact Factor
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Pediatric Rheumatology 04/2012; 9:1-1. · 1.44 Impact Factor
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ABSTRACT: A septic arthritis due to an indolent infection is a challenge for timely diagnosis. In recent years septic arthritides due to Staphylococcus Warneri are increasingly reported, mostly as a complication in patients with prosthetic devices. We report on a case of a 38 year old immunocompetent male with an indolent infection with this commensal of the skin after a stay at an intensive care unit and review the available literature. Tissue cultures obtained by arthroscopy might be helpful in obtaining a correct diagnosis.
The Open Rheumatology Journal 01/2012; 6:310-1.
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ABSTRACT: We explored the attitudes of rheumatology practitioners toward the transition and transfer of adolescents with a rheumatic disorder from pediatric to adult healthcare. Rheumatology practitioners attending the Pediatric Rheumatology European Society (PRES) Congress in 2010 were asked to complete the Questionnaire about Attitudes of Rheumatology Practitioners Toward Transfer and Transition (QUARTT), an instrument that was specifically devised for this study. Overall, 138 healthcare professionals participated (response rate, 55.2%). Participants believed that when patients with an active rheumatic disorder reach adulthood, they should receive medical follow-up from an adult rheumatologist (87%). Only 19% thought that patients should remain under the surveillance of a pediatric rheumatologist. Several initiating factors for transfer were marked as important: readiness of the patient according to the caregiver (62%), age (61%), and psychosocial maturity (49%). A transfer meeting with the patient (76%), a referral letter (73%), and a medical transfer file (64%) were the most preferred transfer communication methods. Joint outpatient clinics, phone calls, and transfer meetings without the patient were considered to be less useful. Pediatric (94%) or adult (83%) rheumatologists, parents (81%), and nurse specialists (74%) were stated as the most important active participants in the transition process. Responders favored essential transition components because young people should be assisted on how to become independent (96%), how to deal with fatigue (91%), and how to establish medication adherence (90%). In conclusion, this study emphasized the importance of transfer to specialized rheumatology care of adolescents with an active rheumatic disease and highlighted transfer initiators and transfer communication tools.
Rheumatology International 12/2011; · 1.88 Impact Factor
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Joel M Kremer,
Anthony S Russell,
Paul Emery,
Carlos Abud-Mendoza,
Jacek Szechinski, Rene Westhovens,
Tracy Li,
Xianhuang Zhou,
Jean-Claude Becker,
Richard Aranda,
Charles Peterfy,
Harry K Genant
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ABSTRACT: To evaluate abatacept treatment over 3 years in patients with rheumatoid arthritis (RA) refractory to methotrexate (MTX).
Patients randomised to abatacept or placebo (+MTX) during the 1-year double-blind period of the Abatacept in Inadequate responders to Methotrexate (AIM) trial received open-label abatacept (+MTX) in the long-term extension (LTE). Safety was assessed for patients who received ≥ 1 dose of abatacept, regardless of randomisation group. Efficacy was assessed for patients randomised to abatacept who entered the LTE.
433 and 219 patients were randomised and treated with abatacept or placebo, respectively; 378 and 161 entered the LTE. At year 3, 440/539 patients were ongoing. No unexpected safety events were observed in the LTE. By year 3, incidence rates of adverse event and serious adverse events were 249.8/100 and 15.1/100 patient-years, respectively. Incidence rates were generally stable over time. At year 3, 84.8%, 63.4% and 37.5% of patients achieved American College of Rheumatology (ACR) criteria of 20, 50 and 70, respectively, compared with 82.3%, 54.3% and 32.4% of patients at year 1. Mean changes in Genant-modified Sharp scores were reduced progressively over 3 years, with significantly greater inhibition during year 3 compared with year 2 (p=0.022 for total score).
In MTX-inadequate responders with RA, abatacept provided consistent safety and sustained efficacy over 3 years. The data suggest an increasing inhibitory disease-modifying effect on radiographic progression.
Annals of the rheumatic diseases 10/2011; 70(10):1826-30. · 8.11 Impact Factor
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ABSTRACT: This article reports 1-year clinical outcomes in the subgroup of patients with rheumatoid arthritis in the Abatacept study to Gauge Remission and joint damage progression in methotrexate-naive patients with Early Erosive rheumatoid arthritis (AGREE) who achieved radiographic nonprogression at the end of the double-blind phase.
Patients who achieved radiographic nonprogression (change from baseline in total Sharp score ≤ 0 at 12 months) with abatacept plus methotrexate (MTX) or MTX alone were eligible for this analysis. Clinical outcomes were remission, defined by 28-joint Disease Activity Score (DAS28) using C-reactive protein (CRP), low Disease Activity Score (LDAS), American College of Rheumatology (ACR) scores, physical function (Health Assessment Questionnaire), and tender and swollen joint counts. Safety was assessed at each visit.
Patients in the abatacept plus MTX and MTX monotherapy groups had similar baseline characteristics and were similar to the overall study population. The proportion of patients who achieved DAS28 (CRP) remission or LDAS was greater with abatacept plus MTX vs MTX alone [43.2% vs 22.7% (p < 0.001) and 57.4% vs 40.6% (p = 0.008), respectively]. More patients receiving abatacept plus MTX achieved key ACR responses, including major clinical response (27.3% vs 11.9%; p < 0.001). Safety profiles were similar in both treatment groups.
More MTX-naive patients with early RA who achieved radiographic nonprogression taking abatacept plus MTX also achieved DAS28 (CRP)-defined remission and LDAS compared with patients who received MTX alone, supporting the use of abatacept as a first-line biologic in combination with disease-modifying antirheumatic drugs.
The Journal of Rheumatology 09/2011; 38(11):2362-8. · 3.69 Impact Factor
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Olga Gorlova,
Jose-Ezequiel Martin,
Blanca Rueda,
Bobby P C Koeleman,
Jun Ying,
Maria Teruel,
Lina-Marcela Diaz-Gallo,
Jasper C Broen,
Madelon C Vonk,
Carmen P Simeon, [......],
Carmen Fonseca,
Christopher P Denton,
Peter K Gregersen,
Sandeep Agarwal,
Shervin Assassi,
Filemon K Tan,
Frank C Arnett,
Timothy R D J Radstake,
Maureen D Mayes,
Javier Martin
PLoS Genetics 08/2011; 7(8). · 8.69 Impact Factor
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Olga Gorlova,
Jose-Ezequiel Martin,
Blanca Rueda,
Bobby P C Koeleman,
Jun Ying,
Maria Teruel,
Lina-Marcela Diaz-Gallo,
Jasper C Broen,
Madelon C Vonk,
Carmen P Simeon, [......],
Carmen Fonseca,
Christopher P Denton,
Peter K Gregersen,
Sandeep Agarwal,
Shervin Assassi,
Filemon K Tan,
Frank C Arnett,
Timothy R D J Radstake,
Maureen D Mayes,
Javier Martin
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ABSTRACT: The aim of this study was to determine, through a genome-wide association study (GWAS), the genetic components contributing to different clinical sub-phenotypes of systemic sclerosis (SSc). We considered limited (lcSSc) and diffuse (dcSSc) cutaneous involvement, and the relationships with presence of the SSc-specific auto-antibodies, anti-centromere (ACA), and anti-topoisomerase I (ATA). Four GWAS cohorts, comprising 2,296 SSc patients and 5,171 healthy controls, were meta-analyzed looking for associations in the selected subgroups. Eighteen polymorphisms were further tested in nine independent cohorts comprising an additional 3,175 SSc patients and 4,971 controls. Conditional analysis for associated SNPs in the HLA region was performed to explore their independent association in antibody subgroups. Overall analysis showed that non-HLA polymorphism rs11642873 in IRF8 gene to be associated at GWAS level with lcSSc (P = 2.32×10(-12), OR = 0.75). Also, rs12540874 in GRB10 gene (P = 1.27 × 10(-6), OR = 1.15) and rs11047102 in SOX5 gene (P = 1.39×10(-7), OR = 1.36) showed a suggestive association with lcSSc and ACA subgroups respectively. In the HLA region, we observed highly associated allelic combinations in the HLA-DQB1 locus with ACA (P = 1.79×10(-61), OR = 2.48), in the HLA-DPA1/B1 loci with ATA (P = 4.57×10(-76), OR = 8.84), and in NOTCH4 with ACA P = 8.84×10(-21), OR = 0.55) and ATA (P = 1.14×10(-8), OR = 0.54). We have identified three new non-HLA genes (IRF8, GRB10, and SOX5) associated with SSc clinical and auto-antibody subgroups. Within the HLA region, HLA-DQB1, HLA-DPA1/B1, and NOTCH4 associations with SSc are likely confined to specific auto-antibodies. These data emphasize the differential genetic components of subphenotypes of SSc.
PLoS Genetics 07/2011; 7(7):e1002178. · 8.69 Impact Factor
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ABSTRACT: To define the burden of hand radiological damage in systemic sclerosis (SSc) patients, compared with a control group.
Both hands of 167 SSc patients and 168 hands (82 right and 86 left) of age- and gender-matched controls were imaged by conventional radiograph. Two musculoskeletal radiologists semiquantitatively scored the following lesions: tuft acro-osteolysis, tuft calcinosis, joint space narrowings, marginal erosions, surface erosions, collapse arthropathies, periarticular calcifications, and juxta-articular osteoporosis, at the following areas: tufts, distal interphalangeal, proximal interphalangeal, metacarpophalangeal, carpal, and first carpometacarpal joints. Clinical and functional characteristics of the 167 SSc patients were obtained from the Belgian Systemic Sclerosis Cohort database.
Tuft acro-osteolysis and calcinosis were the most common findings observed in SSc patients and were almost absent in controls. SSc patients displaying tuft acro-osteolysis/calcinosis suffered from more severe disease. Arthropathies were infrequently detected and mainly consisted of a mixture of osteoarthritis-related changes (joint space narrowing and surface erosions)-also observed in controls-and of 2 types of rare SSc-associated arthropathies: a rheumatoid arthritis-like pattern, characterized by marginal erosions (n = 7 patients), and a collapse arthropathy (n = 6 patients), characterized by pressure erosions and joint subluxation.
Although a rheumatoid arthritis-like or a collapse arthropathy can be observed in SSc patients, arthropathies are less common than previously reported.
Seminars in arthritis and rheumatism 04/2011; 40(5):455-60. · 4.72 Impact Factor
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ABSTRACT: To examine changes in activity participation following abatacept treatment for rheumatoid arthritis (RA), and which factors contributed to such changes.
Data were analyzed from the Abatacept in Inadequate responders to Methotrexate (AIM) and Abatacept Trial in Treatment of Anti-TNF INadequate responders (ATTAIN) clinical trials of abatacept in patients with RA. Activity participation was evaluated by the validated Activity Participation Questionnaire (APaQ), along with measures of clinical response and health-related quality of life. Changes in the APaQ during the two study periods were compared between treatment groups. Multiple regression analyses were performed to investigate the determinants of change in activity participation. The relationship between clinical efficacy measures (including low disease activity state [LDAS], Disease Activity Score 28-defined remission, and European League Against Rheumatism [EULAR] responses) and changes in activity participation were investigated.
Statistically significant, substantive improvements in activity participation were observed over the entire study period in patients treated with abatacept. Abatacept-treated patients showed improvements from baseline of 8.4 and 7.3 days in activity participation, compared with 4.5 and 1.4 days in the placebo group (P < 0.005 vs. placebo in both trials), at the end of AIM and ATTAIN, respectively. The Short Form-36 physical and mental component scores, patient global assessment, and the Health Assessment Questionnaire-Disability Index score were found to be the strongest determinants of changes in activity participation. Patients who achieved LDAS, disease remission and good EULAR responses experienced greater improvements in activity participation measures.
Abatacept treatment substantively and significantly improved patients' ability to participate in their usual activities. The gain in activity was closely related to improvements in clinical status, physical function and quality of life.
Value in Health 02/2011; 14(2):361-70. · 2.19 Impact Factor
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Annals of the rheumatic diseases 01/2011; 70(1):234-5. · 8.11 Impact Factor
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Lara Bossini-Castillo,
Jasper C A Broen,
Carmen P Simeon,
Lorenzo Beretta,
Madelon C Vonk,
Norberto Ortego-Centeno,
Gerard Espinosa,
Patricia Carreira,
María Teresa Camps,
Nuria Navarrete, [......],
Paolo Airó,
Raffaella Scorza,
Jacob M van Laar,
Nicolas Hunzelmann,
Alexander Kreuter,
Ariane Herrick,
Jane Worthington,
Timothy R D J Radstake,
Javier Martín,
Blanca Rueda
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ABSTRACT: The aim of this study was to confirm the influence of TNFSF4 polymorphisms on systemic sclerosis (SSc) susceptibility and phenotypic features.
A total of 8 European populations of Caucasian ancestry were included, comprising 3014 patients with SSc and 3125 healthy controls. Four genetic variants of TNFSF4 gene promoter (rs1234314, rs844644, rs844648 and rs12039904) were selected as genetic markers.
A pooled analysis revealed the association of rs1234314 and rs12039904 polymorphisms with SSc (OR 1.15, 95% CI 1.02 to 1.31; OR 1.18, 95% CI 1.08 to 1.29, respectively). Significant association of the four tested variants with patients with limited cutaneous SSc (lcSSc) was revealed (rs1234314 OR 1.22, 95% CI 1.07 to 1.38; rs844644 OR 0.91, 95% CI 0.83 to 0.99; rs844648 OR 1.10, 95% CI 1.01 to 1.20 and rs12039904 OR 1.20, 95% CI 1.09 to 1.33). Association of rs1234314, rs844648 and rs12039904 minor alleles with patients positive for anti-centromere antibodies (ACA) remained significant (OR 1.23, 95% CI 1.10 to 1.37; OR 1.12, 95% CI 1.01 to 1.25; OR 1.22, 95% CI 1.07 to 1.38, respectively). Haplotype analysis confirmed a protective haplotype associated with SSc, lcSSc and ACA positive subgroups (OR 0.88, 95% CI 0.82 to 0.96; OR 0.88, 95% CI 0.80 to 0.96; OR 0.86, 95% CI 0.77 to 0.97, respectively) and revealed a new risk haplotype associated with the same groups of patients (OR 1.14, 95% CI 1.03 to 1.26; OR 1.20, 95% CI 1.08 to 1.35; OR 1.23, 95% CI 1.07 to 1.42, respectively).
The data confirm the influence of TNFSF4 polymorphisms in SSc genetic susceptibility, especially in subsets of patients positive for lcSSc and ACA.
Annals of the rheumatic diseases 12/2010; 70(4):638-41. · 8.11 Impact Factor
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ABSTRACT: This study is based on the results from a Belgian expanded access program in which patients with active refractory and erosive rheumatoid arthritis (RA) were treated with intravenous infusions of infliximab in combination with methotrexate. The objectives of this study were to evaluate the continuation rate of infliximab and its clinical effect over a 7-year period and to document the reasons for discontinuation.
Between 2000 and 2001, 511 patients with severe and refractory RA were enrolled and treated with infliximab. After 7 years, apart from routine clinical follow-up, treating rheumatologists were asked to complete a questionnaire designed specifically for the present study to evaluate the current therapy with infliximab, the level of disease activity (Disease Activity Score in 28 joints [DAS28]) and the reasons for infliximab discontinuation.
After 7 years, 160 of 511 patients (31%) were still on infliximab treatment. The major reasons for infliximab discontinuation included lack of efficacy (104 patients), adverse events (107 patients) and elective change of therapy (70 patients). The majority of cases of treatment discontinuation for safety reasons occurred during the first 2 years. In contrast, discontinuation due to ineffectiveness showed a more constant rate over the 7-year period. Mean DAS for patients still on treatment with infliximab decreased from 5.7 (standard error [SE] 0.1) at baseline to 3.0 (SE 0.1) at year 4 and remained that low until year 7 (3.0 [SE 0.1]). Low disease activity (defined as DAS28<3.2) was present in 60.9% of patients, and 45.5% achieved remission (DAS28<2.6). DAS28 at the time of treatment discontinuation due to ineffectiveness decreased over the 7-year period from 5.6 (SE 0.3) in 2001 to 4.8 (SE 0.3) in 2008.
This observational study revealed that patients who continue to receive infliximab experience sustained clinical benefit. The majority of safety issues occurred during the first 2 years of infliximab therapy. We observed that the DAS at the time of therapy discontinuation showed a trend to decrease over time.
Arthritis research & therapy 05/2010; 12(3):R77. · 4.27 Impact Factor
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Timothy R D J Radstake,
Olga Gorlova,
Blanca Rueda,
Jose-Ezequiel Martin,
Behrooz Z Alizadeh,
Rogelio Palomino-Morales,
Marieke J Coenen,
Madelon C Vonk,
Alexandre E Voskuyl,
Annemie J Schuerwegh, [......],
Laura Hummers,
J Lee Nelson,
Sandeep K Agarwal,
Shervin Assassi,
Pravitt Gourh,
Filemon K Tan,
Bobby P C Koeleman,
Frank C Arnett,
Javier Martin,
Maureen D Mayes
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ABSTRACT: Systemic sclerosis (SSc) is an autoimmune disease characterized by fibrosis of the skin and internal organs that leads to profound disability and premature death. To identify new SSc susceptibility loci, we conducted the first genome-wide association study in a population of European ancestry including a total of 2,296 individuals with SSc and 5,171 controls. Analysis of 279,621 autosomal SNPs followed by replication testing in an independent case-control set of European ancestry (2,753 individuals with SSc (cases) and 4,569 controls) identified a new susceptibility locus for systemic sclerosis at CD247 (1q22-23, rs2056626, P = 2.09 x 10(-7) in the discovery samples, P = 3.39 x 10(-9) in the combined analysis). Additionally, we confirm and firmly establish the role of the MHC (P = 2.31 x 10(-18)), IRF5 (P = 1.86 x 10(-13)) and STAT4 (P = 3.37 x 10(-9)) gene regions as SSc genetic risk factors.
Nature Genetics 04/2010; 42(5):426-9. · 35.53 Impact Factor
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ABSTRACT: We investigated what it means to patients with juvenile idiopathic arthritis (JIA) to grow up with this disease. A qualitative study was conducted using semi-structured, in-depth interviews of 11 patients with JIA, aged 18-30 years. Interviews were tape recorded and transcribed verbatim. Data were analysed using procedures inherent to the grounded theory approach. Five main themes emerged: physical impact, medication, relationships and family, friends, and perceptions of their future. The physical impact of JIA involved functional limitations, pain, and fatigue. Taking medication properly was difficult; side effects were seen as a problem. With regard to relationships and family, JIA affected the subjects in their roles as family members and affected intimate relationships, pregnancy, and raising children. Indeed, the majority of the patients were afraid to become pregnant or to have children. Most patients found friends who understand their situation and who are a big support. Some patients were afraid of what the future would bring. A better understanding of the psychosocial needs of adolescents with JIA and getting insight into what it means to grow up with this condition will assist healthcare professionals to target interventions that are timely and effective in transitional care to adulthood.
Clinical Rheumatology 04/2010; 30(4):459-65. · 2.00 Impact Factor
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ABSTRACT: Despite important progress in the treatment of rheumatoid arthritis in the last decade, even in the era of tumour necrosis factor (TNF) blockade there is a need for additional therapeutic options in many patients. In recent years three therapies with a distinct mode of action became available: rituximab, an anti-B cell therapy, tocilizumab, an anti IL-6 therapy, and abatacept, a costimulation blocker. Primary efficacy results of all three therapies are comparable at 6 months, nevertheless they have distinct efficacy and safety profiles. In the current review we focus on specific aspects of efficacy and safety of abatacept: increasing clinical and X-ray improvements over time, important and stable responses over several years, timing of response, improvements in patient-centered outcomes, and also long-term safety and easy administration with low rates of perfusion reactions. Currently, head to head comparisons between biologics are still lacking and registry data of drugs with a mode of action different to TNF blockade are still rare. In the meantime detailed analysis of all trials with a drug such as abatacept provides important information for the practicing rheumatologist.
Therapeutic advances in musculoskeletal disease 04/2010; 2(2):89-94.
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Michael Mahler,
Liesbeth Maes,
Daniel Blockmans, Rene Westhovens,
Xavier Bossuyt,
Gabriela Riemekasten,
Sandra Schneider,
Falk Hiepe,
Andreas Swart,
Irmgard Gürtler,
Karl Egerer,
Margrit Fooke,
Marvin J Fritzler
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ABSTRACT: Anti-centromere antibodies (ACA) are useful biomarkers in the diagnosis of systemic sclerosis (SSc). ACA are found in 20 to 40% of SSc patients and, albeit with lower prevalence, in patients with other systemic autoimmune rheumatic diseases. Historically, ACA were detected by indirect immunofluorescence (IIF) on HEp-2 cells and confirmed by immunoassays using recombinant CENP-B. The objective of this study was to evaluate a novel CENP-A peptide ELISA.
Sera collected from SSc patients (n=334) and various other diseases (n=619) and from healthy controls (n=175) were tested for anti-CENP-A antibodies by the novel CENP-A enzyme linked immunosorbent assay (ELISA). Furthermore, ACA were determined in the disease cohorts by IIF (ImmunoConcepts, Sacramento, CA, USA), CENP-B ELISA (Dr. Fooke), EliA CENP (Phadia, Freiburg, Germany) and line-immunoassay (LIA, Mikrogen, Neuried, Germany). Serological and clinical associations of anti-CENP-A with other autoantibodies were conducted in one participating centre. Inhibition experiments with either the CENP-A peptide or recombinant CENP-B were carried out to analyse the specificity of anti-CENP-A and -B antibodies.
The CENP-A ELISA results were in good agreement with other ACA detection methods. According to the kappa method, the qualitative agreements were: 0.73 (vs. IIF), 0.81 (vs. LIA), 0.86 (vs. CENP-B ELISA) and 0.97 (vs. EliA CENP). The quantitative comparison between CENP-A and CENP-B ELISA using 265 samples revealed a correlation value of rho=0.5 (by Spearman equation). The receiver operating characteristic analysis indicated that the discrimination between SSc patients (n=131) and various controls (n=134) was significantly better using the CENP-A as compared to CENP-B ELISA (P<0.0001). Modified Rodnan skin score was significantly lower in the CENP-A negative group compared to the positive patients (P=0.013). Inhibition experiments revealed no significant cross reactivity of anti-CENP-A and anti-CENP-B antibodies. Statistically relevant differences for gender ratio (P=0.0103), specific joint involvement (Jaccoud) (P=0.0006) and anti-phospholipid syndrome (P=0.0157) between ACA positive SLE patients and the entire SLE cohort were observed.
Anti-CENP-A antibodies as determined by peptide ELISA represent a sensitive, specific and independent marker for the detection of ACA and are useful biomarkers for the diagnosis of SSc. Our data suggest that anti-CENP-A antibodies are a more specific biomarker for SSc than antibodies to CENP-B. Furthers studies are required to verify these findings.
Arthritis research & therapy 01/2010; 12(3):R99. · 4.27 Impact Factor
