Rheumatoid Arthritis: Peloso P

Dore RK, Mathews S, Schechtman J, Surbeck W, Mandel D, Patel A, Zhou L, Peloso P. · Robin K. Dore, MD, Inc, Anaheim, CA 92801, USA. · Clin Exp Rheumatol. · Pubmed #17417989 No free full text.

Abstract: OBJECTIVE: To evaluate the immunogenicity, safety, and efficacy of 50 mg/mL liquid etanercept. METHODS: In a multicenter, open-label study, adults with active rheumatoid arthritis (RA) received 50 mg/mL liquid etanercept subcutaneously once weekly for 24 weeks. Immunogenicity was assessed at baseline and weeks 24 and 28, safety at all study visits, and efficacy at baseline and weeks 12 and 24. RESULTS: Of 222 treated patients, 88% completed the study; 81% were women; 84% were white; mean age was 53 years; mean RA duration was 10 years. Antibodies to etanercept, all non-neutralizing, were detected in 12 of 214 patients; 7 of the 12 were borderline positive (antibody titers <1:50). The presence of non-neutralizing anti-etanercept antibodies did not appear to affect clinical safety or efficacy. Few patients reported serious adverse events (6.3%), serious infections (2.3%), or withdrew because of adverse events (4.5%). Most adverse events were mild or moderate. The most common event, injection site reaction, occurred in 29.3% patients. At week 24, 63% of patients achieved an ACR20 response, 36% an ACR50 response, and 14% an ACR70 response. Similar responses were apparent by week 12. Week 24 mean improvement in the Health Assessment Questionnaire disability index scores was 0.6 points; improvement in the Short Form-36 Physical Component Score was 10.0 points. CONCLUSION: The 50 mg/mL liquid etanercept formulation administered once weekly was well tolerated. The incidence of anti-etanercept antibodies, the nature and frequency of adverse events, and improvements in signs and symptoms of RA and patient physical function were similar to those in previous etanercept studies.

Fleischmann R, Baumgartner SW, Weisman MH, Liu T, White B, Peloso P. · University of Texas Southwestern Medical Center at Dallas, 5939 Harry Hines Boulevard, Dallas, Texas 75235, USA. · Ann Rheum Dis. · Pubmed #16150792 links to  free full text

Abstract: OBJECTIVES: To determine the long term safety profile of the tumour necrosis factor (TNF) antagonist etanercept in subjects with rheumatoid arthritis (RA), psoriatic arthritis (PsA), or ankylosing spondylitis (AS) aged > or =65 years in comparison with subjects aged <65 years. METHODS: Safety data from an integrated database of 4322 subjects enrolled in 18 RA trials, 2 PsA trials, and 2 AS trials were analysed. Safety end points included subject incidence of all adverse events (AE), serious adverse events (SAE), infectious events (IE), medically important infections (MII), and deaths. Events of particular interest in subjects treated with TNF modulating biological treatments, including demyelinating diseases, tuberculosis, lymphomas, and cardiovascular diseases, were also evaluated. RESULTS: The incidence of AE, SAE, IE, MII, and malignancies was not significantly raised in elderly subjects in comparison with subjects aged <65 years. No cases of tuberculosis were reported in the trials. Demyelinating diseases were seen only in subjects aged <65 years. The incidence and types of death in the elderly subjects were consistent with the expected rates for subjects of comparable age. CONCLUSIONS: Etanercept is a generally safe and well tolerated biological agent for treatment of rheumatological diseases in the elderly, and the risk of AE in these studies was no greater in subjects aged > or =65 years than in younger subjects.

Bruynesteyn K, Van Der Heijde D, Boers M, Saudan A, Peloso P, Paulus H, Houben H, Griffiths B, Edmonds J, Bresnihan B, Boonen A, Van Der Linden S. · Division of Rheumatology, Maastricht University, Maastricht, The Netherlands. · J Rheumatol. · Pubmed #12415585 No free full text.

Abstract: OBJECTIVE: To evaluate whether knowledge of the chronological sequence influences the sensitivity and specificity of the Sharp/van der Heijde (SvH) and Larsen/Scott (LS) scoring method to detect clinically important progression of joint damage caused by rheumatoid arthritis (RA) in the individual patient and assess whether scoring in chronological order leads to better sensitivity at the cost of lower specificity. METHODS: For both scoring methods, progression scores obtained with (chronological) and without knowledge of the sequence of the films (paired) were compared with the judgment of an international expert panel. This panel assessed whether progression of joint damage seen on films with 1 year intervals was clinically relevant (defined as progression of joint damage that would make clinicians change therapy). The applied thresholds for clinical relevance were (1) the progression scores with the highest accuracy by receiver operating characteristics analyses for the expert opinion, and (2) the smallest progression score that can be detected apart from interobserver measurement error by the scoring method, i.e., the smallest detectable difference (SDD). RESULTS: Progression scores that detected clinically relevant progression most accurately (chronological: 3.0 SvH units and 2.0 LS units; paired: 2.5 SvH units and 1.5 LS units) were smaller than the SDD (chronological 5.0 SvH units and 5.8 LS units; paired 13.8 SvH units and 9.7 LS units). With the SDD as threshold, the sensitivity to detect clinically relevant progression increased significantly from 20 to 60% for the SvH method and from 23 to 33% for the LS method if the sequence of the films was known. The specificity remained good when scoring chronologically: 88% for the SvH and 100% for the LS. CONCLUSION: Our results suggest that knowing the chronological sequence leads to an increase in detecting clinically relevant changes in the patient without serious overestimation of nonrelevant differences. Analyzing a clinical trial should be done preferably by reading films in chronological order.

Bruynesteyn K, van der Heijde D, Boers M, Saudan A, Peloso P, Paulus H, Houben H, Griffiths B, Edmonds J, Bresnihan B, Boonen A, van der Linden S. · Maastricht University, Maastricht, The Netherlands. · Arthritis Rheum. · Pubmed #11953967 No free full text.

Abstract: OBJECTIVE: To assess the minimal clinically important difference (MCID) in joint damage on hand and foot radiographs of patients with early rheumatoid arthritis (RA) as assessed with the Sharp/van der Heijde and Larsen/Scott methods, and to study how the smallest detectable difference (SDD) relates to the MCID for each method. METHODS: The judgments of an international panel of experts on the clinical relevance of progression of joint damage as seen on sets of radiographs obtained at 1-year intervals in 4 clinical settings (early versus late RA and mild versus high disease activity) were used as the external criterion, which was compared with the progression scores as determined by the 2 scoring methods. Progression scores with the highest combined sensitivity and specificity for detecting clinically relevant progression represented the MCID. Subsequently, the sensitivity and specificity of the scoring methods were determined when using the SDD as the threshold for relevant progression, and these were compared with the sensitivity and specificity of the MCID. RESULTS: The panel judged changes in joint damage around the level of the SDD (5.0) of the Sharp/van der Heijde method as minimal clinically important, resulting in satisfactory sensitivity (mean 79%) and specificity (mean 84%) for detecting clinically important progression in the 4 clinical settings when using the SDD as the threshold value. The MCID (mean 2.3) of the Larsen/Scott method was much smaller than its SDD (5.8), and the sensitivity for detecting clinically important progression by applying the SDD as threshold was consequently low (mean 51%), accompanied by high specificity (mean 99%). CONCLUSION: This study suggests that the SDD of the Sharp/van der Heijde method can be used as the MCID, i.e., as the threshold level for individual response criteria. The SDD of the Larsen/Scott method, however, turned out to be too insensitive to use as the threshold for individual clinically relevant change.

Bruynesteyn K, van der Heijde D, Boers M, Lassere M, Boonen A, Edmonds J, Houben H, Paulus H, Peloso P, Saudan A, van der Linden S. · Department of Rheumatology, University Hospital Maastricht, The Netherlands. · J Rheumatol. · Pubmed #11327274 No free full text.

Abstract: To determine the minimal clinically important difference (MCID) between hand and foot films with a 1 year interval assessed with the Sharp/van der Heijde or Larsen/Scott scoring method. Progression scores of the 2 methods were compared with the opinion of an international expert panel on clinical relevance of radiological joint damage in 4 predefined clinical settings. The expert panel consisted of 3 rheumatologists, who evaluated 46 pairs of hand and foot films, taken with 1 year intervals, of patients with early rheumatoid arthritis. Receiver operating characteristics curves analyzed the accuracy of different threshold values (progression scores) of the 2 scoring methods to detect the presence or absence of clinically important difference, as defined by the expert panel as external criterion. The threshold value with the highest accuracy was subsequently chosen as the score representing the MCID. Five Sharp/van der Heijde units and 2 Larsen/Scott units were the best cutoffs. The accompanying sensitivities ranged from 77% to 100% for the Sharp/van der Heijde method and from 73% to 84% for the Larsen/Scott method for the 4 clinical settings. The specificities were between 78% and 84% for the Sharp/van der Heijde method and between 74% and 94% for the Larsen/Scott method. The smallest progression score that can be detected apart from interobserver measurement error, the smallest detectable difference (SDD), was equal to or larger than the calculated MCID, 5 Sharp/van der Heijde units and 6 Larsen/Scott units in our study, if the mean progression scores of the same 2 observers were used. The SDD is a conservative estimate of the MCID; our panel rated progression at or below this level as clinically significant.