Rheumatoid Arthritis: Shadick N

Vera-Llonch M, Massarotti E, Wolfe F, Shadick N, Westhovens R, Sofrygin O, Maclean R, Yuan Y, Oster G. · Policy Analysis Inc., Brookline, MA 02445, USA. · Rheumatology (Oxford). · Pubmed #18356179 links to  free full text

Abstract: OBJECTIVE: To assess cost-effectiveness of abatacept in patients with moderately to severely active RA and inadequate response to MTX. METHODS: We developed a simulation model to depict progression of disability [in terms of the HAQ Disability Index (HAQ-DI)] in women aged 55-64 yrs with moderately to severely active RA and inadequate response to MTX. At model entry, patients were assumed to receive either only MTX or MTX plus abatacept. Patients were then tracked from model entry until death. Future health-state utilities and medical-care costs (except study therapy) were estimated based on predicted values of the HAQ-DI. The model was estimated using data from a Phase III clinical trial of abatacept plus various secondary sources. Cost-effectiveness was expressed in terms of incremental cost (2006 US$) per quality-adjusted life-year (QALY) gained over alternatively 10 yrs and a lifetime. Costs and health effects were both discounted at 3% annually. RESULTS: Over 10 yrs, abatacept would yield 1.2 additional QALYs (undiscounted) per patient (4.6 vs 3.4 for MTX) at an incremental (discounted) cost of $51,426 ($103,601 vs $52,175, respectively); over a lifetime, corresponding figures were 2.0 QALYS (6.8 vs 4.8) and $67,757 ($147,853 vs $80,096). Cost-effectiveness was [mean (95% CI)] $47,910 ($44,641, $52,136) per QALY gained over 10 yrs and $43,041 ($39,070, $46,725) per QALY gained over a lifetime. Findings were robust in sensitivity analyses. CONCLUSION: Abatacept is cost-effective by current standards of medical practice in patients with moderately to severely active RA and inadequate response to MTX.

Solomon DH, Finkelstein JS, Shadick N, LeBoff MS, Winalski CS, Stedman M, Glass R, Brookhart MA, Weinblatt ME, Gravallese EM. · Brigham and Women's Hospital, Division of Rheumatology, Boston, Massachusetts 02115, USA. · Arthritis Rheum. · Pubmed #19479876 No free full text.

Abstract: OBJECTIVE: Among rheumatoid arthritis (RA) patients who have had the disease for 10 years, more than half have focal erosions, and the risk of fracture is doubled. However, there is little information about the potential relationship between focal erosions and bone mineral density (BMD). The aim of this study was to determine whether lower BMD is associated with higher erosion scores among patients with RA. METHODS: We enrolled 163 postmenopausal women with RA, none of whom were taking osteoporosis medications. Patients underwent dual x-ray absorptiometry at the hip and spine and hand radiography, and completed a questionnaire. The hand radiographs were scored using the Sharp method, and the relationship between BMD and erosions was measured using Spearman's correlation coefficients and adjusted linear regression models. RESULTS: Patients had an average disease duration of 13.7 years, and almost all were taking a disease-modifying antirheumatic drug. Sixty-three percent were rheumatoid factor (RF) positive. The median modified Health Assessment Questionnaire score was 0.7, and the average Disease Activity Score in 28 joints was 3.8. The erosion score was significantly correlated with total hip BMD (r=-0.33, P<0.0001), but not with lumbar spine BMD (r=-0.09, P=0.27). Hip BMD was significantly lower in RF-positive patients versus RF-negative patients (P=0.02). In multivariable models that included age, body mass index, and cumulative oral glucocorticoid dose, neither total hip BMD nor lumbar spine BMD was significantly associated with focal erosions. CONCLUSION: Our results suggest that hip BMD is associated with focal erosions among postmenopausal women with RA, but that this association disappears after multivariable adjustment. While BMD and erosions may be correlated with bone manifestations of RA, their relationship is complex and influenced by other disease-related factors.

Vera-Llonch M, Massarotti E, Wolfe F, Shadick N, Westhovens R, Sofrygin O, Maclean R, Li T, Oster G. · From Policy Analysis Inc., Brookline, MA 02445, USA. · J Rheumatol. · Pubmed #18634164 No free full text.

Abstract: OBJECTIVE: To assess cost-effectiveness of abatacept in patients with rheumatoid arthritis (RA) with inadequate response to tumor necrosis factor-alpha antagonists (anti-TNF). METHODS: We developed a simulation model to depict progression of disability [in terms of Health Assessment Questionnaire Disability Index (HAQ-DI)] in women aged 55-64 years with moderately to severely active RA and inadequate response to anti-TNF. At model entry, patients were assumed to receive either oral disease modifying antirheumatic drugs (DMARD) only or oral DMARD plus abatacept. Patients were then tracked from model entry until death. Future health-state utilities and medical-care costs (except study therapy) were estimated based on predicted values of the HAQ-DI. The model was estimated using data from a Phase III clinical trial of abatacept plus secondary sources. Cost-effectiveness was expressed in terms of incremental cost (2006 US$) per quality-adjusted life-year (QALY) gained alternatively over 10 years and a lifetime. Future costs and health effects were discounted at 3% annually. RESULTS: Over 10 years, abatacept would yield 1.0 additional QALY (undiscounted) per patient (4.0 vs 3.0 for oral DMARD) at an incremental (discounted) cost of $45,497 (100,648 vs $55,151) respectively; over a lifetime, corresponding figures were 1.6 QALY (5.8 vs 4.2) and $64,978 ($140,714 vs $82,489). Cost-effectiveness was [mean (95% CI)] $50,576 ($47,056, $54,944) per QALY gained over 10 years, and $45,979 ($42,678, $49,932) per QALY gained over a lifetime. Findings were robust in sensitivity analyses. CONCLUSION: Abatacept is cost-effective by current standards of medical practice in patients with moderately to severely active RA and inadequate response to an anti-TNF.

Johnsen AK, Plenge RM, Butty V, Campbell C, Dieguez-Gonzalez R, Gomez-Reino JJ, Shadick N, Weinblatt M, Gonzalez A, Gregersen PK, Benoist C, Mathis D. · Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts, USA. · Arthritis Rheum. · Pubmed #18576312 links to  free full text

Abstract: OBJECTIVE: It has been suggested that polymorphisms in IL1 are correlated with severe and/or erosive rheumatoid arthritis (RA), but the implicated alleles have differed among studies. The aim of this study was to perform a broad and well-powered search for association between allelic polymorphism in IL1A and IL1B and the susceptibility to or severity of RA. METHODS: Key coding and regulatory regions in IL1A and IL1B were sequenced in 24 patients with RA, revealing 4 novel single-nucleotide polymorphisms (SNPs) in IL1B. These and a comprehensive set of 24 SNPs tagging most of the underlying genetic diversity were genotyped in 3 independent RA case-control sample sets and 1 longitudinal RA cohort, totaling 3,561 patients and 3,062 control subjects. RESULTS: No fully significant associations were observed. Analysis of the discovery case-control sample sets indicated a potential association of IL1B promoter region SNPs with susceptibility to RA (for RA3/A, odds ratio [OR] 1.27, P = 0.0021) or with the incidence of radiographic erosions (for RA4/C, OR 1.56, P = 0.036), but these findings were not replicated in independent case-control samples. No association with rheumatoid factor, anti-cyclic citrullinated peptide, or the Disease Activity Score in 28 joints was found. None of the associations previously observed in other studies were replicated here. CONCLUSION: In spite of a broad and highly powered study, we observed no robust, reproducible association between IL1A/B variants and the susceptibility to or severity of RA in white individuals of European descent. Our results provide evidence that, in the majority of cases, polymorphism in IL1A and IL1B is not a major contributor to genetic susceptibility to RA.

Solomon DH, Stedman M, Licari A, Weinblatt ME, Maher N, Shadick N. · Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA. · Arthritis Rheum. · Pubmed #17330299 links to  free full text

Abstract: OBJECTIVE: With the growth in patient registries in rheumatic disease research, it is important to validate the collected information. We examined the convergent validity of self-reported medication use for rheumatoid arthritis (RA). METHODS: In the setting of the Brigham Rheumatoid Arthritis Sequential Study (BRASS), a large registry of patients with RA, we examined the agreement between patients' self-report of current and past RA medication use and information from medical records. For a sample of patients in BRASS, these 2 sources of information were compared using the kappa statistic as well as the percent agreement. RESULTS: The 91 patients selected for assessment were typical of a prevalent RA cohort: >80% were women and the mean disease duration was 16 years. The agreement for current medication use was excellent, ranging from 0.71 for sulfasalazine to 0.96 for methotrexate. However, for past medication use agreement was lower, ranging from 0.13 for methotrexate to 0.74 for aurothioglucose. The weighted kappa for cumulative oral glucocorticoid dose was 0.67. CONCLUSION: Self-report of current medication use and cumulative oral glucocorticoid dose appears to have moderate to excellent validity. However, self-report of past medication use may not be valid.

Coblyn JS, Shadick N, Helfgott S. · Division of Rheumatology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA. · Arthritis Rheum. · Pubmed #11352235 links to  free full text

Abstract: OBJECTIVE: To determine the frequency of weight loss in patients treated with leflunomide for rheumatoid arthritis at an arthritis referral center. METHODS: We queried 35 rheumatologists at the Robert Breck Brigham Arthritis Center to determine if weight loss had occurred as an adverse event in patients treated with leflunomide between November 1998 and January 2000. Five such patients were identified and their clinical course was reviewed. RESULTS: Five of 70 patients who had begun leflunomide therapy had significant weight loss that could not be linked to other identifiable etiologies. The amount of weight loss was substantial in this group of patients, ranging from 19 pounds to 53 pounds. All patients had normal levels of thyroid-stimulating hormone and no other gastrointestinal complaints; evaluation revealed no other cause for the weight loss. Despite the significant weight loss, 4 of the 5 patients continued to take the drug due to its efficacy. CONCLUSION: Significant weight loss is a potential adverse event in patients with rheumatoid arthritis treated with leflunomide. Awareness of this may obviate the need for extensive medical evaluations.

Roubenoff R, Beckman E, Weinblatt M, Shadick N, Gregersen PK. · No affiliation provided · Ann Intern Med. · Pubmed #18316760 links to  free full text

This publication has no abstract.

Costenbader KH, Glass R, Cui J, Shadick N. · No affiliation provided · JAMA. · Pubmed #17090761 No free full text.

This publication has no abstract.