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Daniel J Wallace, Caroline Gordon,
Vibeke Strand,
Kathryn Hobbs,
Michelle Petri,
Kenneth Kalunian,
Frederic Houssiau,
Paul P Tak,
David A Isenberg,
Lexy Kelley,
Brian Kilgallen,
Anna N Barry,
William A Wegener,
David M Goldenberg
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ABSTRACT: Objective. To evaluate epratuzumab treatment in patients with moderately-to-severely active SLE in two international, randomized, controlled trials (ALLEVIATE-1 and -2) and an open-label extension study (SL0006).Methods. Ninety ALLEVIATE patients (43% BILAG A, median BILAG score 12.0) received standard of care plus 10 total doses of placebo (n = 37) or 360 mg/m(2) (n = 42) or 720 mg/m(2) (n = 11) epratuzumab, administered across 12-week cycles for up to 48 weeks, with BILAG assessments every 4 weeks. Patients were followed for ≥6 months and their data combined for analysis. The primary endpoint was BILAG response at week 12 (all BILAG A scores reduced to B/C/D and B scores to C/D, no new A and <2 new B scores). Twenty-nine patients continued in SL0006, receiving 12-week cycles of 360 mg/m(2) epratuzumab; this interim analysis was performed at median 120 weeks (range 13-184) of exposure.Results. Both ALLEVIATE trials were discontinued prematurely because of interruption in drug supply. Exploratory pooled analyses found that responses at week 12 were 15/34 (44.1%) and 2/10 (20.0%) for epratuzumab 360 and 720 mg/m(2), respectively, vs 9/30 (30.0%) for placebo. Total BILAG scores were lower in both epratuzumab arms vs placebo at week 48 and at all but two time points. The incidence of adverse events was similar between groups. In SL0006, median total BILAG score was 8.0 (n = 29) at study entry and 7.0 (n = 19) at week 100, with no additional safety signals.Conclusion. This initial efficacy and safety profile of epratuzumab supports its continued development for SLE treatment.
Rheumatology (Oxford, England) 03/2013; · 4.24 Impact Factor
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Arthritis care & research. 03/2013;
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Sasha Bernatsky,
Rosalind Ramsey-Goldman,
Jeremy Labrecque,
Lawrence Joseph,
Jean-Francois Boivin,
Michelle Petri,
Asad Zoma,
Susan Manzi,
Murray B Urowitz,
Dafna Gladman, [......],
Jean-Luc Senécal,
Michel Zummer,
Janet E Pope,
Stephanie Ensworth,
Hani El-Gabalawy,
Timothy McCarthy,
Lene Dreyer,
John Sibley,
Yvan St Pierre,
Ann E Clarke
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ABSTRACT: OBJECTIVE: To update estimates of cancer risk in SLE relative to the general population. METHODS: A multisite international SLE cohort was linked with regional tumor registries. Standardized incidence ratios (SIRs) were calculated as the ratio of observed to expected cancers. RESULTS: Across 30 centres, 16,409 patients were observed for 121,283 (average 7.4) person-years. In total, 644 cancers occurred. Some cancers, notably hematologic malignancies, were substantially increased (SIR 3.02, 95% confidence interval, CI, 2.48, 3.63), particularly non-Hodgkin's lymphoma, NHL (SIR 4.39, 95% CI 3.46, 5.49) and leukemia. In addition, increased risks of cancer of the vulva (SIR 3.78, 95% CI 1.52, 7.78), lung (SIR 1.30, 95% CI 1.04, 1.60), thyroid (SIR 1.76, 95% CI 1.13, 2.61) and possibly liver (SIR 1.87, 95% CI 0.97, 3.27) were suggested. However, a decreased risk was estimated for breast (SIR 0.73, 95% CI 0.61-0.88), endometrial (SIR 0.44, 95% CI 0.23-0.77), and possibly ovarian cancers (0.64, 95% CI 0.34-1.10). The variability of comparative rates across different cancers meant that only a small increased risk was estimated across all cancers (SIR 1.14, 95% CI 1.05, 1.23). CONCLUSION: These data estimate only a small increased risk in SLE (versus the general population) for cancer over-all. However, there is clearly an increased risk of NHL, and cancers of the vulva, lung, thyroid, and possibly liver. It remains unclear to what extent the association with NHL is mediated by innate versus exogenous factors. Similarly, the etiology of the decreased breast, endometrial, and possibly ovarian cancer risk is uncertain, though investigations are ongoing.
Journal of Autoimmunity 02/2013; · 7.37 Impact Factor
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Daniel J Wallace,
Kenneth Kalunian,
Michelle A Petri,
Vibeke Strand,
Frederic A Houssiau,
Marilyn Pike,
Brian Kilgallen,
Sabine Bongardt,
Anna Barry,
Lexy Kelley, Caroline Gordon
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ABSTRACT: OBJECTIVE: To identify a suitable dosing regimen of the CD22-targeted monoclonal antibody epratuzumab in adults with moderately to severely active systemic lupus erythematosus (SLE). METHODS: A phase IIb, multicentre, randomised controlled study (NCT00624351) was conducted with 227 patients (37-39 per arm) receiving either: placebo, epratuzumab 200 mg cumulative dose (cd) (100 mg every other week (EOW)), 800 mg cd (400 mg EOW), 2400 mg cd (600 mg weekly), 2400 mg cd (1200 mg EOW), or 3600 mg cd (1800 mg EOW). The primary endpoint (not powered for significance) was the week 12 responder rate measured using a novel composite endpoint, the British Isles Lupus Assessment Group (BILAG)-based Combined Lupus Assessment (BICLA). RESULTS: Proportion of responders was higher in all epratuzumab groups than with placebo (overall treatment effect test p=0.148). Exploratory pairwise analysis demonstrated clinical improvement in patients receiving a cd of 2400 mg epratuzumab (OR for 600 mg weekly vs placebo: 3.2 (95% CI 1.1 to 8.8), nominal p=0.03; OR for 1200 mg EOW vs placebo: 2.6 (0.9 to 7.1), nominal p=0.07). Post-hoc comparison of all 2400 mg cd patients versus placebo found an overall treatment effect (OR=2.9 (1.2 to 7.1), nominal p=0.02). Incidence of adverse events (AEs), serious AEs and infusion reactions was similar between epratuzumab and placebo groups, without decreases in immunoglobulin levels and only partial reduction in B-cell levels. CONCLUSIONS: Treatment with epratuzumab 2400 mg cd was well tolerated in patients with moderately to severely active SLE, and associated with improvements in disease activity. Phase III studies are ongoing.
Annals of the rheumatic diseases 01/2013; · 8.11 Impact Factor
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Sasha Bernatsky,
Rosalind Ramsey-Goldman,
Lawrence Joseph,
Jean-Francois Boivin,
Karen H Costenbader,
Murray B Urowitz,
Dafna D Gladman,
Paul R Fortin,
Ola Nived,
Michelle A Petri, [......],
Torsten Witte,
Susan G Barr,
Lindsey A Criswell,
Gunnar K Sturfelt,
Irene Blanco,
Candace H Feldman,
Lene Dreyer,
Neha M Patel,
Yvan St Pierre,
Ann E Clarke
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ABSTRACT: OBJECTIVE: To examine disease activity versus treatment as lymphoma risk factors in systemic lupus erythematosus (SLE). METHODS: We performed case-cohort analyses within a multisite SLE cohort. Cancers were ascertained by regional registry linkages. Adjusted HRs for lymphoma were generated in regression models, for time-dependent exposures to immunomodulators (cyclophosphamide, azathioprine, methotrexate, mycophenolate, antimalarial drugs, glucocorticoids) demographics, calendar year, Sjogren's syndrome, SLE duration and disease activity. We used adjusted mean SLE Disease Activity Index scores (SLEDAI-2K) over time, and drugs were treated both categorically (ever/never) and as estimated cumulative doses. RESULTS: We studied 75 patients with lymphoma (72 non-Hodgkin, three Hodgkin) and 4961 cancer-free controls. Most lymphomas were of B-cell origin. As is seen in the general population, lymphoma risk in SLE was higher in male than female patients and increased with age. Lymphomas occurred a mean of 12.4 years (median 10.9) after SLE diagnosis. Unadjusted and adjusted analyses failed to show a clear association of disease activity with lymphoma risk. There was a suggestion of greater exposure to cyclophosphamide and to higher cumulative steroids in lymphoma cases than the cancer-free controls. CONCLUSIONS: In this large SLE sample, there was a suggestion of higher lymphoma risk with exposure to cyclophosphamide and high cumulative steroids. Disease activity itself was not clearly associated with lymphoma risk. Further work will focus on genetic profiles that might interact with medication exposure to influence lymphoma risk in SLE.
Annals of the rheumatic diseases 01/2013; · 8.11 Impact Factor
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Ben Parker,
Murray B Urowitz,
Dafna D Gladman,
Mark Lunt,
Sang-Cheol Bae,
Jorge Sanchez-Guerrero,
Juanita Romero-Diaz, Caroline Gordon,
Daniel J Wallace,
Ann E Clarke, [......],
Meggan Mackay,
Manuel Ramos-Casals,
Raymond F van Vollenhoven,
Kenneth C Kalunian,
Guillermo Ruiz-Irastorza,
Sam Lim,
Diane L Kamen,
Christine A Peschken,
Murat Inanc,
Ian N Bruce
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ABSTRACT: BACKGROUND: The metabolic syndrome (MetS) may contribute to increased cardiovascular risk in systemic lupus erythematosus (SLE). We aimed to examine the association of demographic factors, lupus phenotype and therapy exposure with the presence of MetS. METHODS: The Systemic Lupus International Collaborating Clinics Registry for Atherosclerosis inception cohort enrolled recently diagnosed (<15 months) SLE patients from 30 centres across 11 countries from 2000. Clinical, laboratory and therapeutic data were collected according to a standardised protocol. MetS was defined according to the 2009 consensus statement from the International Diabetes Federation. Univariate and backward stepwise multivariate logistic regression were used to assess the relationship of individual variables with MetS. RESULTS: We studied 1686 patients, of whom 1494 (86.6%) had sufficient data to determine their MetS status. The mean (SD) age at enrolment and disease duration was 35.2 years (13.4) and 24.1 weeks (18.0), respectively. MetS was present at the enrolment visit in 239 (16%). In backward stepwise multivariable regression analysis, higher daily average prednisolone dose (mg) (OR 1.02, 95% CI 1.00 to 1.03), older age (years) (OR 1.04, 95% CI 1.03 to 1.06), Korean (OR 6.33, 95% CI 3.68 to 10.86) and Hispanic (OR 6.2, 95% CI 3.78 to 10.12) ethnicity, current renal disease (OR 1.79, 95% CI 1.14 to 2.80) and immunosuppressant use (OR 1.81, 95% CI 1.18 to 2.78) were associated with MetS. CONCLUSIONS: Renal lupus, higher corticosteroid doses, Korean and Hispanic ethnicity are associated with MetS in SLE patients. Balancing disease control and minimising corticosteroid exposure should therefore be at the forefront of personalised treatment decisions in SLE patients.
Annals of the rheumatic diseases 09/2012; · 8.11 Impact Factor
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Chee-Seng Yee, Caroline Gordon,
David A Isenberg,
Bridget Griffiths,
Lee-Suan Teh,
Ian N Bruce,
Yasmeen Ahmad,
Anisur Rahman,
Athiveeraramapandian Prabu,
Mohammed Akil,
Neil McHugh,
Christopher Edwards,
David D'Cruz,
Munther A Khamashta,
Vernon T Farewell
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ABSTRACT: Objective. This was an exploratory analysis to develop a new way of representing BILAG-2004 system scores longitudinally that would be clinically meaningful and easier to analyse in comparison with multiple categorical variables. Methods. Data from a multicentre longitudinal study of SLE patients (the BILAG-2004 index and therapy collected at every visit) were used. External responsiveness analysis of the index suggested the possibility of using counts of systems with specified transitions in scores as a basis to analyse the system scores. Exploratory analyses with multinomial logistic regression were used to examine the appropriateness of this new method of analysing BILAG-2004 system scores. Receiver operating characteristic (ROC) curve analysis was used to assess the performance of this approach. Results. There were 1414 observations from 347 patients. A novel method was devised based on counts of systems with defined transitions in score (BILAG-2004 systems tally, BST). It has six components (systems with major deterioration, systems with minor deterioration, systems with persistent significant activity, systems with major improvement, systems with minor improvement and systems with persistent minimal or no activity). This was further simplified (simplified BST, sBST) into three components (systems with active/worsening disease, systems with improving disease and systems with persistent minimal or no activity). Both versions had expected associations with change in therapy. ROC curve analyses demonstrated that both versions had similar good performance characteristics (areas under the curve >0.80) in predicting increase in therapy. Conclusion. The BST and sBST provide alternative approaches to representing BILAG-2004 disease activity longitudinally. Further validation of their use is required.
Rheumatology (Oxford, England) 08/2012; 51(11):2099-105. · 4.24 Impact Factor
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ABSTRACT: Objective. To assess the inter-rater reliability of the BILAG2004-Pregnancy index for assessment of SLE disease activity in pregnancy. Methods. Pregnant SLE patients were recruited from four centres and assessed separately by two raters/physicians in routine clinical practice. Disease activity was determined using the BILAG2004-Pregnancy index. Reliability was assessed using level of agreement, κ-statistics and analysis of disagreement. Major disagreement was defined as a score difference of A and C/D/E or B and D/E between the two raters, and minor disagreement was a score difference of A and B or B and C between raters. Results. A total of 30 patients (63.3% Caucasian, 13.3% Afro-Caribbean, 16.7% South Asian) were recruited. The majority of patients had low-level disease activity according to the local rater's assessment, and there was no grade A activity, with grade B activity present in the following systems: mucocutaneous (nine patients), musculoskeletal (two patients), cardiorespiratory (one patient) and renal (one patient). The distribution of disease activity was similar to the external rater's assessment. Good levels of agreement (>70%) were achieved in all systems. κ-statistics were not appropriate for use in the gastrointestinal, ophthalmic, constitutional and neuropsychiatric systems, as there was minimal variation between patients but good levels of agreement otherwise. There were three major disagreements (0.1 per patient, all differences between B and D/E) and five minor disagreements (0.17 per patient). Conclusion. The BILAG2004-Pregnancy index is reliable for assessment of disease activity in pregnant SLE patients.
Rheumatology (Oxford, England) 07/2012; 51(10):1877-80. · 4.24 Impact Factor
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Michelle Petri,
Ana-Maria Orbai,
Graciela S Alarcón, Caroline Gordon,
Joan T Merrill,
Paul R Fortin,
Ian N Bruce,
David Isenberg,
Daniel J Wallace,
Ola Nived, [......],
Kristjan Steinsson,
Andrew G Franks,
Lisa Sigler,
Suhail Hameed,
Hong Fang,
Ngoc Pham,
Robin Brey,
Michael H Weisman,
Gerald McGwin,
Laurence S Magder
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ABSTRACT: The Systemic Lupus International Collaborating Clinics (SLICC) group revised and validated the American College of Rheumatology (ACR) systemic lupus erythematosus (SLE) classification criteria in order to improve clinical relevance, meet stringent methodology requirements, and incorporate new knowledge regarding the immunology of SLE.
The classification criteria were derived from a set of 702 expert-rated patient scenarios. Recursive partitioning was used to derive an initial rule that was simplified and refined based on SLICC physician consensus. The SLICC group validated the classification criteria in a new validation sample of 690 new expert-rated patient scenarios.
Seventeen criteria were identified. In the derivation set, the SLICC classification criteria resulted in fewer misclassifications compared with the current ACR classification criteria (49 versus 70; P = 0.0082) and had greater sensitivity (94% versus 86%; P < 0.0001) and equal specificity (92% versus 93%; P = 0.39). In the validation set, the SLICC classification criteria resulted in fewer misclassifications compared with the current ACR classification criteria (62 versus 74; P = 0.24) and had greater sensitivity (97% versus 83%; P < 0.0001) but lower specificity (84% versus 96%; P < 0.0001).
The new SLICC classification criteria performed well in a large set of patient scenarios rated by experts. According to the SLICC rule for the classification of SLE, the patient must satisfy at least 4 criteria, including at least one clinical criterion and one immunologic criterion OR the patient must have biopsy-proven lupus nephritis in the presence of antinuclear antibodies or anti-double-stranded DNA antibodies.
Arthritis & Rheumatism 05/2012; 64(8):2677-86. · 7.87 Impact Factor
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John G Hanly,
Murray B Urowitz,
Li Su, Caroline Gordon,
Sang-Cheol Bae,
Jorge Sanchez-Guerrero,
Juanita Romero-Diaz,
Daniel J Wallace,
Ann E Clarke,
Em Ginzler, [......],
Rf van Vollenhoven,
Kenneth C Kalunian,
Guillermo Ruiz-Irastorza,
Sam Lim,
Diane L Kamen,
Christine A Peschken,
Murat Inanc,
Chris Theriault,
Kara Thompson,
Vernon Farewell
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ABSTRACT: The aim of this study was to describe the frequency, attribution, outcome and predictors of seizures in systemic lupus erythematosus (SLE).
The Systemic Lupus International Collaborating Clinics, or SLICC, performed a prospective inception cohort study. Demographic variables, global SLE disease activity (SLE Disease Activity Index 2000), cumulative organ damage (SLICC/American College of Rheumatology Damage Index (SDI)) and neuropsychiatric events were recorded at enrolment and annually. Lupus anticoagulant, anticardiolipin, anti-β(2) glycoprotein-I, antiribosomal P and anti-NR2 glutamate receptor antibodies were measured at enrolment. Physician outcomes of seizures were recorded. Patient outcomes were derived from the SF-36 (36-Item Short Form Health Survey) mental component summary and physical component summary scores. Statistical analyses included Cox and linear regressions.
The cohort was 89.4% female with a mean follow-up of 3.5±2.9 years. Of 1631 patients, 75 (4.6%) had ≥1 seizure, the majority around the time of SLE diagnosis. Multivariate analysis indicated a higher risk of seizures with African race/ethnicity (HR (CI): 1.97 (1.07 to 3.63); p=0.03) and lower education status (1.97 (1.21 to 3.19); p<0.01). Higher damage scores (without neuropsychiatric variables) were associated with an increased risk of subsequent seizures (SDI=1:3.93 (1.46 to 10.55); SDI=2 or 3:1.57 (0.32 to 7.65); SDI≥4:7.86 (0.89 to 69.06); p=0.03). There was an association with disease activity but not with autoantibodies. Seizures attributed to SLE frequently resolved (59/78 (76%)) in the absence of antiseizure drugs. There was no significant impact on the mental component summary or physical component summary scores. Antimalarial drugs in the absence of immunosuppressive agents were associated with reduced seizure risk (0.07 (0.01 to 0.66); p=0.03).
Seizures occurred close to SLE diagnosis, in patients with African race/ethnicity, lower educational status and cumulative organ damage. Most seizures resolved without a negative impact on health-related quality of life. Antimalarial drugs were associated with a protective effect.
Annals of the rheumatic diseases 04/2012; 71(9):1502-9. · 8.11 Impact Factor
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ABSTRACT: Individuals with systemic lupus erythematosus (SLE) have an increased susceptibility to certain types of cancer. Given concerns focused on this issue, we present a review of this important topic.
In non-Hodgkin lymphoma (NHL), a several-fold increased risk is seen in SLE versus the general population. It has long been suspected that immunosuppressive drugs play a role in this risk, but there may be other important driving factors as well. Lupus disease activity may itself heighten the risk of lymphoma in diseases like SLE. Lung cancer risk also is increased in SLE; smoking appears to drive this risk. Additionally, cervical dysplasia risk is increased in SLE, particularly with immunosuppressive drug exposure. An altered clearance of cancer-related viral agents in SLE (due to the disease and/or immunosuppression) may contribute to this risk and may also drive the risk for other cancers (such as vulvovaginal and hepatic carcinomas) in SLE. On the positive side, one new and significant finding is that SLE patients seem to have a decreased risk of certain nonhematologic cancers (breast, ovarian, endometrial, and prostate).
Though much has been learnt so far regarding the risk in SLE, much yet remains unknown.
Current opinion in rheumatology 03/2012; 24(2):177-81. · 4.60 Impact Factor
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ABSTRACT: SLE is a multi-system, autoimmune condition that can influence both male and female fertility. Inability to conceive may be attributed to several factors that may act singly or in combination: (i) older age in patients with SLE compared with healthy controls; (ii) disease-related infertility; and (iii) infertility through gonadotoxic treatments. In addition, psychosocial factors related to the disease may lower fecundity and may be associated with apparent infertility. Many therapeutic avenues are open to counteract reproductive damage in the management of SLE and to assist conception once infertility is diagnosed. These treatments can include the administration of gonadotrophin-receptor hormone analogues while receiving CYC treatment, the use of assisted reproductive technologies, such as in vitro fertilization and psychosocial intervention to promote a healthier relationship with their partner. Knowledge of how these reproductive problems occur and its prevention/treatment in SLE patients should avert irreversible infertility as well as give hope to SLE patients with infertility.
Rheumatology (Oxford, England) 06/2011; 50(9):1551-8. · 4.24 Impact Factor
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Evelyne Vinet,
Ann E Clarke, Caroline Gordon,
Murray B Urowitz,
John G Hanly,
Christian A Pineau,
David Isenberg,
Anisur Rahman,
Daniel Wallace,
Graciela S Alarcón,
Ian Bruce,
Michelle Petri,
Mary Ann Dooley,
Kenneth Kalunian,
Peter Maddison,
Cynthia Aranow,
Ronald van Vollenhoven,
Sasha Bernatsky
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ABSTRACT: Multiple disease-related factors may limit the number of children born to women with systemic lupus erythematosus (SLE). We calculated live births in women with SLE and compared this with general population rates.
We studied women with SLE from a subset of centers participating in the Systemic Lupus International Collaborating Clinics Prospective Inception Cohort Study of SLE. Women diagnosed as having SLE before age 50 years were included. Using age, calendar-period, and country-specific general population birth rates, we calculated the standardized incidence ratio (SIR) of observed to expected live births. We also performed a multivariate analysis with the SIR as the dependent variable to explore potential predictors of live births.
A total of 339 women with SLE were studied. The number of live births over the interval (n = 313) was substantially below that which would be expected (n = 479; SIR 0.65, 95% confidence interval [95% CI] 0.58-0.73). In the multivariate analyses, black race/ethnicity (SIR 1.47, 95% CI 1.08-2.00) and being married or living common-law (SIR 2.04, 95% CI 1.52-2.74) were associated with increased live births (relative to what would be expected). There were trends for fewer live births in women exposed to cyclophosphamide (SIR 0.88, 95% CI 0.56-1.38) and in those with high disease activity (mean SLE Disease Activity Index 2000 update score ≥5; SIR 0.82, 95% CI 0.54-1.25).
Overall, we found that women with SLE have fewer live births compared with the general population. Marital status, race/ethnicity, and possibly clinical factors may mediate this effect.
Arthritis care & research. 03/2011; 63(7):1068-72.
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Chee-Seng Yee,
Vernon T Farewell,
David A Isenberg,
Bridget Griffiths,
Lee-Suan Teh,
Ian N Bruce,
Yasmeen Ahmad,
Anisur Rahman,
Athiveeraramapandian Prabu,
Mohammed Akil,
Neil McHugh,
Christopher Edwards,
David D'Cruz,
Munther A Khamashta, Caroline Gordon
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ABSTRACT: To examine SLEDAI-2000 cut-off scores for definition of active SLE and to determine the sensitivity to change of SLEDAI-2000 for the assessment of SLE disease activity and minimal clinically meaningful changes in score.
Data from two multi-centre studies were used in the analysis: in a cross-sectional and a longitudinal fashion. At every assessment, data were collected on SLEDAI-2000 and treatment. The cross-sectional analysis with receiver operating characteristic (ROC) curves was used to examine the appropriate SLEDAI-2000 score to define active disease and increase in therapy was the reference standard. In the longitudinal analysis, sensitivity to change of SLEDAI-2000 was assessed with multinomial logistic regression. ROC curves analysis was used to examine possible cut-points in score changes associated with change in therapy, and mean changes were estimated.
In the cross-sectional analysis, the most appropriate cut-off scores for active disease were 3 or 4. In the longitudinal analysis, the best model for predicting treatment increase was with the change in SLEDAI-2000 score and the score from the previous visit as continuous variables. The use of cut-points was less predictive of treatment change than the use of continuous score. The mean difference in the change in SLEDAI-2000 scores, adjusted for prior score, between patients with treatment increase and those without was 2.64 (95% CI 2.16, 3.14).
An appropriate SLEDAI-2000 score to define active disease is 3 or 4. SLEDAI-2000 index is sensitive to change. The use of SLEDAI-2000 as a continuous outcome is recommended for comparative purposes.
Rheumatology (Oxford, England) 01/2011; 50(5):982-8. · 4.24 Impact Factor
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Kathleen McElhone,
Madhura Castelino,
Janice Abbott,
Ian N Bruce,
Yasmeen Ahmad,
Joanna Shelmerdine,
Kate Peers,
David Isenberg,
Ada Ferenkeh-Koroma,
Bridget Griffiths,
Mohammed Akil,
Peter Maddison, Caroline Gordon,
Lee-Suan Teh
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ABSTRACT: Having developed and validated a disease-specific health-related quality of life (HRQOL) measure for patients with systemic lupus erythematosus (SLE), the LupusQoL, we determined its relationship to demographic and clinical measurements in a group of patients with SLE.
A group of 322 outpatients completed the LupusQoL. Demographic (age, sex, marital status, ethnicity) and clinical variables (disease duration, disease activity, damage) were recorded. Associations between the 8 LupusQoL domains and age, disease duration, disease activity, and damage were explored using Spearman's correlation coefficients. Differences in LupusQoL scores were examined for sex and marital status using the Mann-Whitney U test. Ethnic groups were compared using ANOVA.
All domains of LupusQoL were impaired, with fatigue (56.3) being the worst affected and body image (80.0) the least. The correlations between the LupusQoL domain scores and age (r = -0.01 to -0.22) and disease duration (r = 0 to 0.16) were absent or weak. Similarly, there were no significant differences in the LupusQoL scores regarding sex, marital status, or the 3 main ethnic groups (Black-Caribbean, Asian, White). Although there were statistically significant correlations between the scores of the LupusQoL domains and some scores of the British Isles Lupus Assessment Group index (r = -0.22 to 0.09) and the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (r = -0.29 to 0.21), these were weak.
HRQOL was impaired in this cohort of outpatients with SLE as assessed by the validated lupus-specific LupusQoL. There were no clinically important associations between the 8 domains of the LupusQoL and clinical or demographic variables in this group of patients. Thus, the LupusQoL is a relatively independent outcome measure in patients with SLE.
The Journal of Rheumatology 11/2010; 37(11):2273-9. · 3.69 Impact Factor
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ABSTRACT: Systemic lupus erythematosus is a complex multisystem autoimmune disease that affects 1 in 2000 adult women in the United Kingdom. Lupus affects Afrocaribbeans and South Asians more frequently and more severely than white British. The disease can affect almost any part of the body and is characterised by remission and relapses. It is most common in women of reproductive age but can present at any age from 1 to 90 years and in men, but the diagnosis is probably missed in some men. It is important to distinguish active lupus features due to inflammatory and thrombotic mechanisms from chronic damage and to be aware that infection is an important trigger that may co-exist or mimic lupus activity. The disease is associated with a variety of autoantibodies that can help in making the diagnosis. Monitoring the disease is usually done using a clinical disease activity index such as the BILAG index, anti-dsDNA antibodies, C3 and C4 levels. Anti-C1q antibodies may have a role in monitoring the disease and in predicting those at risk of renal involvement or flare. The prognosis depends on the organs involved. There is an increased risk of premature atherosclerosis as a complication of lupus and this and infection are the most common causes of death in lupus patients.
Autoimmunity reviews 11/2010; 10(1):43-5. · 6.37 Impact Factor
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Monika Ostensen,
Antonio Brucato,
Howard Carp,
Christina Chambers,
Radboud J E M Dolhain,
Andrea Doria,
Frauke Förger, Caroline Gordon,
Sinuhe Hahn,
Munther Khamashta, [......],
J Lee Nelson,
Ann Parke,
Michelle Petri,
Luigi Raio,
Guillermo Ruiz-Irastorza,
Clovis A Silva,
Angela Tincani,
Peter M Villiger,
Dorothea Wunder,
Maurizio Cutolo
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ABSTRACT: Despite evidence for the important role of oestrogens in the aetiology and pathophysiology of chronic immune/inflammatory diseases, the previous view of an unequivocal beneficial effect of oestrogens on RA compared with a detrimental effect on SLE has to be reconsidered. Likewise, the long-held belief that RA remits in the majority of pregnant patients has been challenged, and shows that only half of the patients experience significant improvement when objective disease activity measurements are applied. Pregnancies in patients with SLE are mostly successful when well planned and monitored interdisciplinarily, whereas a small proportion of women with APS still have adverse pregnancy outcomes in spite of the standard treatment. New prospective studies indicate better outcomes for pregnancies in women with rare diseases such as SSc and vasculitis. Fertility problems are not uncommon in patients with rheumatic disease and need to be considered in both genders. Necessary therapy, shortly before or during the pregnancy, demands taking into account the health of both mother and fetus. Long-term effects of drugs on offspring exposed in utero or during lactation is a new area under study as well as late effects of maternal rheumatic disease on children.
Rheumatology (Oxford, England) 11/2010; 50(4):657-64. · 4.24 Impact Factor
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ABSTRACT: Systemic lupus erythematosus (SLE) is an autoimmune disease that is associated with the production of autoantibodies, and with considerable morbidity and mortality. There has been much interest in developing more specific therapies for this disease, which is currently managed with immunosuppressive drugs, predominantly corticosteroids, azathioprine, methotrexate and cyclophosphamide, in combination with hydroxychloroquine. Mycophenolate mofetil has been demonstrated to be as efficacious as cyclophosphamide in patients with lupus nephritis, and is being used increasingly in the clinic despite not being licensed for this indication. Novel methods of reducing autoantibody formation in SLE include the use of mAbs that modulate and/or deplete B-cells (anti-CD22 and anti-CD20 antibodies, respectively), or that interfere with the stimulatory effects of the soluble factor B-lymphocyte stimulator (anti-BLys antibodies). Alternative approaches include the use of atacicept (Merck Serono), a transmembrane activator and calcium modulator ligand interactor (TACI)-Ig fusion protein, which inhibits B-cell stimulation by binding to BLys and a profileration-inducing ligand (APRIL), or toleragens such as abetimus. Blocking costimulatory molecule interactions, such as the CD40-CD40 ligand interaction with mAbs and the CD28-B7 interaction with a soluble cytotoxic T-lymphocyte antigen 4 (CTLA-4)-IgG1 construct (abatacept), has also been attempted as a therapeutic strategy for SLE. The most promising strategy for a new drug for SLE is belimumab (Human Genome Sciences/GlaxoSmithKline), an anti-BLys antibody, as two phase III clinical trials with this drug recently met their primary endpoints. In this review, these novel approaches to the treatment of SLE, including the potential of targeting cytokine pathways involved in autoimmunity, are discussed.
Current opinion in investigational drugs (London, England: 2000) 11/2010; 11(11):1256-64. · 3.31 Impact Factor
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Rheumatology (Oxford, England) 06/2010; 49(6):1025-7. · 4.24 Impact Factor
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Bridget Griffiths,
Paul Emery,
Vicky Ryan,
David Isenberg,
Mohammed Akil,
Robert Thompson,
Peter Maddison,
Ian D Griffiths,
Alice Lorenzi,
Sarah Miles,
Deva Situnayake,
Lee Suan Teh,
Mike Plant,
Christina Hallengren,
Ola Nived,
Gunnar Sturfelt,
Kuntal Chakravarty,
Tim Tait, Caroline Gordon
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ABSTRACT: To determine whether low-dose ciclosporin was a more effective corticosteroid-sparing agent than AZA in patients with SLE.
Patients with SLE requiring a change or initiation of a corticosteroid-sparing agent and who were taking > or =15 mg of prednisolone/day were randomized to receive either ciclosporin or AZA during this 12-month open-label multi-centre trial. There were strict guidelines for the reduction of prednisolone. The primary outcome was the absolute mean change in prednisolone.
Eighty-nine patients were randomized. Using an intention-to-treat analysis, the absolute mean change in prednisolone dose between baseline and 12 months, adjusted for baseline prednisolone dose, was 9.0 mg for ciclosporin (95% CI 7.2, 10.8) and 10.7 mg for AZA (95% CI 8.8, 12.7). The difference in the change between treatment groups was -1.7 mg (95% CI -4.4, 0.9; P = 0.2). No significant differences were detected for the secondary outcomes: change in disease activity [classic British Isles Lupus Assessment Group (BILAG) index], number of flares, development of new damage or change in quality of life. A similar number of patients in each arm stopped the study drugs due to adverse events and ineffectiveness. No patient developed severe hypertension or a persistent rise in creatinine. One patient in the ciclosporin arm developed a significant increase in proteinuria due to disease activity.
Both drugs were effective corticosteroid-sparing agents. Ciclosporin was not a more effective corticosteroid-sparing agent. Ciclosporin may be considered in patients who are unable to tolerate AZA. Patients on ciclosporin require close monitoring of blood pressure and creatinine.
Current Controlled Trials, http://www.controlled-trials.com/, ISRCTN35919612.
Rheumatology (Oxford, England) 04/2010; 49(4):723-32. · 4.24 Impact Factor
