Rheumatoid Arthritis: van de Putte L

Hartman M, van Ede A, Severens JL, Laan RF, van de Putte L, van der Wilt GJ. · Department of Medical Technology Assessment, University Medical Centre, Nijmegen, The Netherlands. · J Rheumatol. · Pubmed #15124248 No free full text.

Abstract: OBJECTIVE: To determine cost-effectiveness of folic or folinic acid supplementation in patients with rheumatoid arthritis (RA) who started methotrexate (MTX) treatment. METHODS: An economic evaluation, performed alongside a randomized, double blind, placebo controlled trial with followup of 48 weeks. Patients started MTX with placebo (n = 137), folic acid (n = 133), or folinic acid (n = 141). Outcome measures were drug survival and quality-adjusted life-years (QALY), measured with the EuroQol questionnaire. Both medical and nonmedical costs were analyzed. RESULTS: Drug survival after 48 weeks was 60% for placebo, 81% for folic acid, and 87% for folinic acid. QALY during a 48 week period were 0.55 (95% CI 0.52-0.58) in the placebo group, 0.55 (95% CI 0.52-0.58) in the folic acid group, and 0.58 (95% CI 0.56-0.60) in the folinic acid group. Mean medical costs were 1398 US dollars (placebo), 1409 US dollars (folic acid), and 1776 US dollars (folinic acid). Mean total costs were 3339 US dollars, 3632 US dollars, and 3296 US dollars, respectively. CONCLUSION: In terms of resource deployment, no statistically significant difference was found between the 3 strategies. The preferred strategy consists of folic acid supplementation because of improved drug survival.

Zandbelt MM, de Wilde P, van Damme P, Hoyng CB, van de Putte L, van den Hoogen F. · Department of Rheumatology, University Medical Center St. Radboud, Nijmegen, The Netherlands. · J Rheumatol. · Pubmed #14705226 No free full text.

Abstract: OBJECTIVE: This pilot study evaluated the effect of anti-tumor necrosis factor-a antiinflammatory treatment with etanercept (Enbrel(R)) on sicca, systemic, and histological signs in patients with primary Sjögren's syndrome (SS). METHODS: Fifteen patients with well defined primary SS were treated with 25 mg etanercept subcutaneously twice per week during 12 weeks, with followup visits at Weeks 18 and 24. Evaluation measures included a Multidimensional Fatigue Inventory (MFI) questionnaire, serological monitoring, salivary flow tests, Schirmer test, rose bengal cornea staining, and tear film breakup time. A sublabial minor salivary gland biopsy was performed at baseline and at Week 12 and lymphocytic focus score and percentage IgA-containing plasma cells (IgA%) were assessed. RESULTS: No increase of salivary or lachrymal gland function was observed in any participant. In 4 patients a decrease of fatigue complaints was noted, which was also reflected by decreased scores in the MFI questionnaire. Reduced erythrocyte sedimentation rate was observed in 3 of 4 patients with reduced fatigue. No significant change of lymphocyte focus score or IgA% was observed. A repeated treatment up to 26 weeks showed the same results. CONCLUSION: A 12-week or prolonged treatment of etanercept 25 mg twice weekly did not appear to reduce sicca symptoms and signs in SS. However, etanercept treatment may be beneficial in a small subgroup of SS patients with severe fatigue. Etanercept 25 mg twice weekly did not affect minor salivary gland biopsy results.

Rau R, Sander O, van Riel P, van de Putte L, Hasler F, Zaug M, Kneer J, van der Auwera P, Stevens RM, Anonymous00147. · Department of Rheumatology, Evangelisches Fachkrankenhaus, Ratingen, Germany. · J Rheumatol. · Pubmed #12672184 No free full text.

Abstract: OBJECTIVE: To determine the optimal dose regimen for intravenous Ro 45-2081 (lenercept) in patients with rheumatoid arthritis (RA) by evaluating efficacy, safety, tolerability, and pharmacokinetic and pharmacodynamic characteristics. METHODS: Adult patients with longstanding RA who were taking stable doses of nonsteroidal antiinflammatory drug and/or low dose corticosteroids but who had stopped their previous disease-modifying antirheumatic drug were randomly assigned to receive 3 intravenous infusions, one every 4 weeks, of placebo or Ro 45-2081 in a double blind, placebo controlled, parallel group multicenter trial. Patients received one of the following: (1) placebo, (2) low dose Ro 45-2081 (0.05 mg/kg, maximum 5 mg), (3) middle dose (mid-dose) Ro 45-2081 (0.2 mg/kg, maximum 20 mg), or (4) high dose Ro 45-2081 (0.5 mg/kg, maximum 50 mg). Efficacy measures included change from baseline in number of swollen joints and tender joints, scores on physician and patient assessments of disease activity, and patient assessment of pain, as well as acute phase reactants. RESULTS: Patients treated with Ro 45-2081 exhibited improvement after one day of the first intravenous infusion. This treatment benefit maximized by 2 weeks but diminished thereafter. After the second and third infusion, improvement was of shorter duration as non-neutralizing anti-Ro 45-2081 antibodies developed and accelerated clearance of Ro 45-2081. There were no antibodies after the first infusion. This made efficacy transient in the mid-dose group and modest in the low and high dose groups at 12 weeks of treatment, resulting in no statistical differences at most time points or doses of Ro 45-2081. The majority of adverse experiences were mild or moderate, and were not related or only remotely related to study drug. No clinically relevant changes in mean laboratory values were reported. The third dose pharmacokinetic measurements showed that the average Ro 45-2081 clearance rate more than doubled compared with the first dosing interval, thus reducing the average Ro 45-2081 AUC by 36%. CONCLUSION: Intravenous Ro 45-2081 every 4 weeks proved to be well tolerated and transiently effective in the mid-dose group and modestly effective in the low and high dose groups in patients with longstanding RA. The interactions between Ro 45-2081, its non-neutralizing anti-Ro 45-2081 antibody, and the clinical benefit remain complex, but affected efficacy over the 12 weeks of treatment as Ro 45-2081 concentrations fell.

den Broeder A, van de Putte L, Rau R, Schattenkirchner M, Van Riel P, Sander O, Binder C, Fenner H, Bankmann Y, Velagapudi R, Kempeni J, Kupper H. · Department of Rheumatology, University Medical Center Nijmegen, Nijmegen, The Netherlands. · J Rheumatol. · Pubmed #12415583 No free full text.

Abstract: OBJECTIVE: To assess the pharmacokinetics, safety profile, and efficacy of the fully human anti-tumor necrosis factor-alpha (anti-TNF-alpha) monoclonal antibody adalimumab (D2E7) in patients with long-standing, active rheumatoid arthritis (RA). METHODS: This was a randomized, double blind, placebo controlled study of single intravenous injections of ascending doses (0.5 to 10 mg/kg) of adalimumab in 5 cohorts of 24 patients each (18 adalimumab and 6 placebo in all cohorts except the 0.5 mg/kg cohort of 17 adalimumab, 7 placebo). A total of 120 patients participated (adalimumab 89, placebo 31). The clinical response was measured by changes in composite scores defined by the criteria of the European League Against Rheumatism (EULAR) and the American College of Rheumatology. RESULTS: Single doses of adalimumab showed a rapid onset of clinical effect (24 hours to 1 week), with peak efficacy at 1 to 2 weeks that was sustained for at least 4 weeks and for as long as 3 months in some patients. EULAR response was seen at least once during the 4 week period after drug injection in 29% of patients in the placebo group as well as in 41%, 78%, 72%, 89%, and 100% in the 0.5, 1, 3, 5, and 10 mg/kg groups, respectively. No dose related increases in adverse events were observed in the adalimumab patients compared with the placebo group. Adalimumab systemic drug exposure (AUC0-( )) increased linearly with an increase in dose. The mean total serum clearance was 0.012 to 0.017 l/h, and the steady-state volume of distribution ranged from 4.7 to 5.5 l. The estimated mean terminal half-life ranged from 10.0 to 13.6 days for the 5 cohorts, with an overall mean half-life of 12 days. CONCLUSION: Treatment with the fully human Mab adalimumab was safe and well tolerated when administered as a single intravenous injection at doses up to 10 mg/kg, and was associated with a clinically significant improvement in the signs and symptoms of active RA.

Eijsbouts A, van den Hoogen F, Laan RF, Hermus RM, Sweep FC, van de Putte L. · No affiliation provided · J Rheumatol. · Pubmed #10529161 No free full text.

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Teixeira VH, Pierlot C, Migliorini P, Balsa A, Westhovens R, Barrera P, Alves H, Vaz C, Fernandes M, Pascual-Salcedo D, Bombardieri S, Dequeker J, Radstake TR, Van Riel P, van de Putte L, Lopes-Vaz A, Bardin T, Prum B, Cornélis F, Petit-Teixeira E, Anonymous00058. · GenHotel-EA3886, Evry University - Paris 7 University Medical School, AutoCure European Consortium, Evry-Genopole, France. · Arthritis Res Ther. · Pubmed #19302705 links to  free full text

Abstract: INTRODUCTION: A candidate gene approach, in a large case-control association study in the Dutch population, has shown that a 480 kb block on chromosome 4q27 encompassing KIAA1109/Tenr/IL2/IL21 genes is associated with rheumatoid arthritis. Compared with case-control association studies, family-based studies have the added advantage of controlling potential differences in population structure. Therefore, our aim was to test this association in populations of European origin by using a family-based approach. METHODS: A total of 1,302 West European white individuals from 434 trio families were genotyped for the rs4505848, rs11732095, rs6822844, rs4492018 and rs1398553 polymorphisms using the TaqMan Allelic discrimination assay (Applied Biosystems). The genetic association analyses for each SNP and haplotype were performed using the Transmission Disequilibrium Test and the genotype relative risk. RESULTS: We observed evidence for association of the heterozygous rs4505848-AG genotype with rheumatoid arthritis (P = 0.04); however, no significance was found after Bonferroni correction. In concordance with previous findings in the Dutch population, we observed a trend of undertransmission for the rs6822844-T allele and rs6822844-GT genotype to rheumatoid arthritis patients. We further investigated the five SNP haplotypes of the KIAA1109/Tenr/IL2/IL21 gene region. We observed, as described in the Dutch population, a nonsignificant undertransmission of the AATGG haplotype to rheumatoid arthritis patients. CONCLUSIONS: Using a family-based study, we have provided a trend for the association of the KIAA1109/Tenr/IL2/IL21 gene region with rheumatoid arthritis in populations of European descent. Nevertheless, we failed to replicate a significant association of this region in our rheumatoid arthritis family sample. Further investigation of this region, including detection and testing of all variants, is required to confirm rheumatoid arthritis association.

Kurreeman FA, Rocha D, Houwing-Duistermaat J, Vrijmoet S, Teixeira VH, Migliorini P, Balsa A, Westhovens R, Barrera P, Alves H, Vaz C, Fernandes M, Pascual-Salcedo D, Michou L, Bombardieri S, Radstake T, van Riel P, van de Putte L, Lopes-Vaz A, Prum B, Bardin T, Gut I, Cornelis F, Huizinga TW, Petit-Teixeira E, Toes RE, Anonymous00030. · Leiden University Medical Center, Leiden, The Netherlands. · Arthritis Rheum. · Pubmed #18759306 No free full text.

Abstract: OBJECTIVE: We recently showed, using a candidate gene approach in a case-control association study, that a 65-kb block encompassing tumor necrosis factor receptor-associated factor 1 (TRAF1) and C5 is strongly associated with rheumatoid arthritis (RA). Compared with case-control association studies, family-based studies have the added advantage of controlling potential differences in population structure and are not likely to be hampered by variation in population allele frequencies, as is seen for many genetic polymorphisms, including the TRAF1/C5 locus. The aim of this study was to confirm this association in populations of European origin by using a family-based approach. METHODS: A total of 1,356 western European white individuals from 452 "trio" families were genotyped for the rs10818488 polymorphism, using the TaqMan allelic discrimination assay. RESULTS: We observed evidence for association, demonstrating departure from Mendel's law, with an overtransmission of the rs10818488 A allele (A = 55%; P = 0.036). By taking into consideration parental phenotypes, we also observed an increased A allele frequency in affected versus unaffected parents (A = 64%; combined P = 0.015). Individuals carrying the A allele had a 1.2-fold increased risk of developing RA (allelic odds ratio 1.24, 95% confidence interval 1.04-1.50). CONCLUSION: Using a family-based study that is robust against population stratification, we provide evidence for the association of the TRAF1/C5 rs10818488 A allele and RA in populations of European descent, further substantiating our previous findings. Future functional studies should yield insight into the biologic relevance of this locus to the pathways involved in RA.

Jacq L, Garnier S, Dieudé P, Michou L, Pierlot C, Migliorini P, Balsa A, Westhovens R, Barrera P, Alves H, Vaz C, Fernandes M, Pascual-Salcedo D, Bombardieri S, Dequeker J, Radstake TR, Van Riel P, van de Putte L, Lopes-Vaz A, Glikmans E, Barbet S, Lasbleiz S, Lemaire I, Quillet P, Hilliquin P, Teixeira VH, Petit-Teixeira E, Mbarek H, Prum B, Bardin T, Cornélis F, Anonymous00262. · GenHotel-EA3886, Evry-Paris VII Universities, 91057 Evry-Genopole cedex, France. · Arthritis Res Ther. · Pubmed #17615072 links to  free full text

Abstract: The integrin alpha(v)beta3, whose alpha(v) subunit is encoded by the ITGAV gene, plays a key role in angiogenesis. Hyperangiogenesis is involved in rheumatoid arthritis (RA) and the ITGAV gene is located in 2q31, one of the suggested RA susceptibility loci. Our aim was to test the ITGAV gene for association and linkage to RA in a family-based study from the European Caucasian population. Two single nucleotide polymorphisms were genotyped by PCR-restriction fragment length polymorphism in 100 French Caucasian RA trio families (one RA patient and both parents), 100 other French families and 265 European families available for replication. The genetic analyses for association and linkage were performed using the comparison of allelic frequencies (affected family-based controls), the transmission disequilibrium test, and the genotype relative risk.We observed a significant RA association for the C allele of rs3738919 in the first sample (affected family-based controls, RA index cases 66.5% versus controls 56.7%; P = 0.04). The second sample showed the same trend, and the third sample again showed a significant RA association. When all sets were combined, the association was confirmed (affected family-based controls, RA index cases 64.6% versus controls 58.1%; P = 0.005). The rs3738919-C allele was also linked to RA (transmission disequilibrium test, 56.5% versus 50% of transmission; P = 0.009) and the C-allele-containing genotype was more frequent in RA index cases than in controls (RA index cases 372 versus controls 339; P = 0.002, odds ratio = 1.94, 95% confidence interval = 1.3-2.9). The rs3738919-C allele of the ITGAV gene is associated with RA in the European Caucasian population, suggesting ITGAV as a new minor RA susceptibility gene.

Michou L, Lasbleiz S, Rat AC, Migliorini P, Balsa A, Westhovens R, Barrera P, Alves H, Pierlot C, Glikmans E, Garnier S, Dausset J, Vaz C, Fernandes M, Petit-Teixeira E, Lemaire I, Pascual-Salcedo D, Bombardieri S, Dequeker J, Radstake TR, Van Riel P, van de Putte L, Lopes-Vaz A, Prum B, Bardin T, Dieudé P, Cornélis F, Anonymous00173. · GenHotel-EA 3886, University Evry-Paris 7 Medical School, Member of the AutoCure European Consortium, CP5727, 91057 Evry-Genopole Cedex, France. · Proc Natl Acad Sci U S A. · Pubmed #17237219 links to  free full text

Abstract: The tyrosine phosphatase PTPN22 allele 1858T has been associated with rheumatoid arthritis (RA) and other autoimmune diseases. RA is the most frequent of those multifactorial diseases. The RA association was usually restricted to serum rheumatoid factor positive disease (RF+). No interaction was shown with HLA-DRB1, the first RA gene. Many case-control studies replicated the RA association, showing an allele frequency increase of approximately 5% on average and large variations of population allele frequencies (2.1-15.5%). In multifactorial diseases, the final proof for a new susceptibility allele is provided by departure from Mendel's law (50% transmission from heterozygous parents). For PTPN22-1858T allele, convincing linkage proof was available only for type 1 diabetes. We aimed at providing this proof for RA. We analyzed 1,395 West European Caucasian individuals from 465 "trio" families. We replicated evidence for linkage, demonstrating departure from Mendel's law in this subset of early RA onset patients. We estimated the overtransmission of the 1858T allele in RF+ families: T = 63%, P < 0.0007. The 1858T allele frequency increased from 11.0% in controls to 17.4% in RF+ RA for the French Caucasian population and the susceptibility genotype (1858T/T or T/C) from 20.2% to 31.6% [odds ratio (OR) = 1.8 (1.2-2.8)]. In conclusion, we provided the linkage proof for the PTPN22-1858T allele and RF+ RA. With diabetes and RA, PTPN22 is therefore a "linkage-proven" autoimmunity gene. PTPN22 accounting for approximately 1% of the RA familial aggregation, many new genes could be expected that are as many leads to definitive therapy for autoimmune diseases.

van Lankveld W, van't Pad Bosch P, van der Schaaf D, Dapper M, de Waal Malefijt M, van de Putte L. · Sint Maartenskliniek Research and the Departments of Rheumatology and Orthopaedics, Sint Maartenskliniek, Nijmegen, The Netherlands. · J Hand Surg Am. · Pubmed #11040307 No free full text.

Abstract: Short-term effect of hand surgery on hand function in activities of daily life (dexterity) and pain were studied in 70 patients with rheumatoid arthritis. Only surgical interventions aimed at improvement of function and/or pain relief were included in the study. Patients were assessed before surgery and 6 and 12 months after surgery. Clinical change in the surgical group was observed in the number of painful and swollen joints, observed dexterity, and pain in the hand. Six months after surgery 74% of the patients showed positive clinical change in hand functioning and/or hand pain. Clinical effects remained stable between 6 and 12 months after surgical assessments. Both change in observed dexterity and pain had an independent impact on the patient's satisfaction with the results of the surgery.

van Lankveld W, Näring G, van't Pad Bosch P, van de Putte L. · Sint Maartenskliniek Research, Nijmegen, The Netherlands. · J Behav Med. · Pubmed #10984866 No free full text.

Abstract: The objective of this study was to analyze the effect of coping with pain in rheumatoid arthritis (RA) on subsequent changes in psychological distress and disease impact. A sample of 109 randomly selected RA patients was asked to participate in a longitudinal study. Patients were measured at baseline and after 3 years. Both measurements were completed in 80 patients. At each assessment the following variables were assessed: disease activity, pain, physical and psychological distress, disease impact, and coping. The relation between coping with pain at baseline and subsequent changes in psychological distress and disease impact was analyzed using stepwise regression. Disease status variables assessed at baseline and after 3 years were entered in the regression analysis as control variables. Results show that cognitive coping with pain at baseline was not related to subsequent changes in psychological distress or disease impact. On the other hand, behavioral pain coping assessed at baseline was related to subsequent changes in psychological distress and disease impact. "Decreasing activity" was related to an increase in self-reported psychological distress and disease impact after controlling for disease status at both assessments. It was concluded that cognitive pain coping did not predict any subsequent changes in psychological distress or disease impact. "Decreasing activity" as a behavioral pain coping style has a negative effect on subsequent changes in psychological distress and disease impact.

van Lankveld W, Näring G, van 't Pad Bosch P, van de Putte L. · Sint Maartenskliniek Research, Nijmegen, The Netherlands. · J Rheumatol. · Pubmed #10332968 No free full text.

Abstract: OBJECTIVE: To assess the relationship between behavioral coping and dexterity in rheumatoid arthritis (RA) after controlling for disease activity, impairment of the hands, and pain. METHODS: A random sample of 109 patients with RA was assessed twice within one year. Dexterity, disease activity, and impairment of the hands were measured using observational methods. Pain and coping with RA were assessed using self-report instruments. RESULTS: Correlational findings showed that "decreasing activity" to cope with pain was negatively related to dexterity. "Pacing" as a way of coping with limitations was positively related to dexterity. Both relations were significant after controlling for duration of disease, impairment of hands, disease activity, and pain. "Decreasing activity" as a way of coping with pain was related to a decrease in dexterity in the subsequent year, after controlling for baseline measurements of dexterity, impairment, and disease activity as well as measurements of current disease activity and pain. "Pacing" as a way of coping with limitations was unrelated to subsequent changes in dexterity, after controlling for the above mentioned variables. CONCLUSION: Behaviorial coping is related to current and subsequent levels of dexterity. Therefore, it is concluded that more attention should be given to behaviorial coping in both research and clinical practice.

Teixeira VH, Dieudé P, Michou L, Migliorini P, Balsa A, Westhovens R, Barrera P, Alves H, Vaz C, Fernandes M, Pascual-Salcedo D, Bombardieri S, Dequeker J, Radstake TR, Van Riel P, van de Putte L, Lopes-Vaz A, Bardin T, Cornélis F, Anonymous00026, Petit-Teixeira E. · No affiliation provided · Ann Rheum Dis. · Pubmed #19213753 No free full text.

This publication has no abstract.