Treatment Algorithms in Systemic Lupus Erythematosus Muangchan, Chayawee; van Vollenhoven, Ronald F.; Bernatsky, Sasha R. ...
Arthritis Care and Research,
September 2015, Letnik:
67, Številka:
9
Journal Article
Recenzirano
Odprti dostop
Objective
To establish agreement on systemic lupus erythematosus (SLE) treatment.
Methods
SLE experts (n = 69) were e‐mailed scenarios and indicated preferred treatments. Algorithms were constructed ...and agreement determined (≥50% respondents indicating ≥70% agreement).
Results
Initially, 54% (n = 37) responded suggesting treatment for scenarios; 13 experts rated agreement with scenarios. Fourteen of 16 scenarios had agreement as follows: discoid lupus: first‐line therapy was topical agents and hydroxychloroquine and/or glucocorticoids then azathioprine and subsequently mycophenolate (mofetil); uncomplicated cutaneous vasculitis: initial treatment was glucocorticoids ± hydroxychloroquine ± methotrexate, followed by azathioprine or mycophenolate and then cyclophosphamide; arthritis: initial therapy was hydroxychloroquine and/or glucocorticoids, then methotrexate and subsequently rituximab; pericarditis: first‐line therapy was nonsteroidal antiinflammatory drugs, then glucocorticoids with/without hydroxychloroquine, then azathioprine, mycophenolate, or methotrexate and finally belimumab or rituximab, and/or a pericardial window; interstitial lung disease/alveolitis: induction was glucocorticoids and mycophenolate or cyclophosphamide, then rituximab or intravenous gamma globulin (IVIG), and maintenance followed with azathioprine or mycophenolate; pulmonary hypertension: glucocorticoids and mycophenolate or cyclophosphamide and an endothelin receptor antagonist were initial therapies, subsequent treatments were phosphodiesterase‐5 inhibitors and then prostanoids and rituximab; antiphospholipid antibody syndrome: standard anticoagulation with/without hydroxychloroquine, then a thrombin inhibitor for venous thrombosis, versus adding aspirin or platelet inhibition drugs for arterial events; mononeuritis multiplex and central nervous system vasculitis: first‐line therapy was glucocorticoids and cyclophosphamide followed by maintenance with azathioprine or mycophenolate, and then rituximab, IVIG, or plasmapheresis; and serious lupus nephritis: first‐line therapy was glucocorticoids and mycophenolate, then cyclophosphamide then rituximab.
Conclusion
We established variable agreement on treatment approaches. For some treatment decisions there was good agreement between experts even if no randomized controlled trial data were available.
Objective
Fatigue is a common symptom in systemic lupus erythematosus (SLE), and engaging in physical activity may reduce fatigue. We aimed to characterize relationships between fatigue, other health ...status measures assessed with the Patient Reported Outcomes Measurement Information System (PROMIS) instruments, and accelerometer-based physical activity measurements in patients with SLE. The internal consistency of each PROMIS measure in our SLE sample was also evaluated.
Methods
This cross-sectional study analyzed 123 adults with SLE. The primary fatigue outcome was Fatigue Severity Scale score. Secondary outcomes were PROMIS standardized T-scores in seven health status domains. Accelerometers were worn for seven days, and mean daily minutes of light, moderate/vigorous, and bouted (10 minutes) moderate/vigorous physical activity were estimated. Cronbach’s alpha was determined for each PROMIS measure to assess internal consistency. Relationships between Fatigue Severity Scale, PROMIS, and physical activity were summarized with Spearman partial correlation coefficients (r), adjusted for average daily accelerometer wear time.
Results
Mean Fatigue Severity Scale score (4.3, SD 1.6) was consistent with clinically relevant levels of fatigue. Greater daily and bouted moderate/vigorous physical activity minutes correlated with lower Mean Fatigue Severity Scale score (r = −0.20, p = 0.03 and r = −0.30, p = 0.0007, respectively). For PROMIS, bouted moderate/vigorous physical activity minutes correlated with less fatigue (r = −0.20, p = 0.03). PROMIS internal consistency was excellent, with Cronbach’s alpha > 0.90 for each domain. Mean PROMIS T-scores for fatigue, pain interference, anxiety, sleep disturbance, sleep-related impairment, and physical function were worse than reported for the general US population. More moderate/vigorous physical activity minutes were associated with less pain interference (r = −0.22, p = 0.01). Both light physical activity and moderate/vigorous physical activity minutes correlated with better physical function (r = 0.19, p = 0.04 and r = 0.25, p = 0.006, respectively).
Conclusion
More time spent in moderate/vigorous physical activity was associated with less fatigue (Fatigue Severity Scale and PROMIS), less pain interference, and better physical function (PROMIS). PROMIS had excellent internal consistency in our SLE sample, and six of seven PROMIS measures indicated poorer average health status in SLE patients compared with the general US population.
Objective
To describe vascular events during an 8‐year followup in a multicenter systemic lupus erythematosus (SLE) inception cohort and their attribution to atherosclerosis.
Methods
Clinical data, ...including comorbidities, were recorded yearly. Vascular events were recorded and attributed to atherosclerosis or not. All of the events met standard clinical criteria. Factors associated with atherosclerotic vascular events were analyzed using descriptive statistics, t‐tests, and chi‐square tests. Stepwise multivariate logistic regression was used to assess the association of factors with vascular events attributed to atherosclerosis.
Results
Since 2000, 1,249 patients have been entered into the cohort. There have been 97 vascular events in 72 patients, including: myocardial infarction (n = 13), angina (n = 15), congestive heart failure (n = 24), peripheral vascular disease (n = 8), transient ischemic attack (n = 13), stroke (n = 23), and pacemaker insertion (n = 1). Fifty of the events were attributed to active lupus, 31 events in 22 patients were attributed to atherosclerosis, and 16 events were attributed to other causes. The mean ± SD time from diagnosis to the first atherosclerotic event was 2.0 ± 1.5 years. Compared with patients followed for 2 years without atherosclerotic events (n = 615), at enrollment, patients with atherosclerotic vascular events were more frequently white, men, older at diagnosis of SLE, obese, smokers, hypertensive, and had a family history of coronary artery disease. On multivariate analysis, only male sex and older age at diagnosis were associated factors.
Conclusion
In an inception cohort with SLE followed for up to 8 years, there were 97 vascular events, but only 31 were attributable to atherosclerosis. Patients with atherosclerotic events were more likely to be men and to be older at diagnosis of SLE.
One challenge in caring for patients with systemic lupus erythematosus (SLE) is a paucity of approved therapeutics for treatment of the diverse disease manifestations. In the last 60 years, only one ...drug, belimumab, has been approved for SLE treatment. Critical evaluation of investigator initiated and pharma-sponsored randomized controlled trials (RCTs) highlights barriers to successful drug development in SLE, including disease heterogeneity, inadequate trial size or duration, insufficient dose finding before initiation of large trials, handling of background medications, and choice of primary endpoint. Herein we examine lessons learned from landmark SLE RCTs and subsequent advances in trial design, as well as discuss efforts to address limitations in current SLE outcome measures that will improve detection of true therapeutic responses in future RCTs.
Objective
We describe disease activity, damage, and the accrual of key autoantibodies in an inception systemic lupus erythematosus (SLE) cohort.
Methods
The Systemic Lupus International Collaborating ...Clinics (SLICC) International Research Network, comprising 27 centers from 11 countries, has followed an inception cohort of SLE patients yearly according to a standardized protocol. Of these patients, 298 were followed for a minimum of 5 years and constitute the study population. Disease activity was assessed using the SLE Disease Activity Index 2000 (SLEDAI‐2K) and damage was assessed using the SLICC/American College of Rheumatology Damage Index (SDI). Antinuclear antibody (ANA), anti‐DNA, and anticardiolipin antibody (aCL) levels and lupus anticoagulant were assessed yearly. Descriptive statistics were generated and repeated‐measures general linear models were used to evaluate SLEDAI‐2K and SDI over time between whites and nonwhites.
Results
Of the 298 patients, 87% were women, 55% were white, 12% were African American, 14% were Asian, 16% were Hispanic, and 2% were categorized as “other.” At enrollment, the mean age was 35.3 years, the mean SLEDAI‐2K score was 5.9, and the mean disease duration was 5.5 months. Mean SLEDAI‐2K scores decreased in the first year and then remained low. SLEDAI‐2K scores were significantly lower at each year in whites compared to nonwhites. Mean SDI scores increased progressively over 5 years; there was no significant difference between whites and nonwhites. As expected, ANA positivity was high and anti‐DNA positivity was relatively low at enrollment, and both increased over 5 years. Although lupus anticoagulant increased slightly over 5 years, aCL positivity did not.
Conclusion
Disease activity in newly diagnosed patients decreases over their first 5 years, while damage increases. Antibody positivity ran variable courses over this period.
Objective
To determine the level of agreement of disease flare severity (distinguishing severe, moderate, and mild flare and persistent disease activity) in a large paper‐patient exercise involving ...988 individual cases of systemic lupus erythematosus.
Methods
A total of 988 individual lupus case histories were assessed by 3 individual physicians. Complete agreement about the degree of flare (or persistent disease activity) was obtained in 451 cases (46%), and these provided the reference standard for the second part of the study. This component used 3 flare activity instruments (the British Isles Lupus Assessment Group BILAG 2004, Safety of Estrogens in Lupus Erythematosus National Assessment SELENA flare index SFI and the revised SELENA flare index rSFI). The 451 patient case histories were distributed to 18 pairs of physicians, carefully randomized in a manner designed to ensure a fair case mix and equal distribution of flare according to severity.
Results
The 3‐physician assessment of flare matched the level of flare using the 3 indices, with 67% for BILAG 2004, 72% for SFI, and 70% for rSFI. The corresponding weighted kappa coefficients for each instrument were 0.82, 0.59, and 0.74, respectively. We undertook a detailed analysis of the discrepant cases and several factors emerged, including a tendency to score moderate flares as severe and persistent activity as flare, especially when the SFI and rSFI instruments were used. Overscoring was also driven by scoring treatment change as flare, even if there were no new or worsening clinical features.
Conclusion
Given the complexity of assessing lupus flare, we were encouraged by the overall results reported. However, the problem of capturing lupus flare accurately is not completely solved.
An increased lymphoma risk is well documented in systemic lupus (SLE). Less attention has been focused on women's cancers, even though SLE affects mostly females. Our objective was to estimate the ...risk of breast, ovarian, and endometrial cancers in SLE, relative to the general population.
Data were included from five recent studies of large SLE cohorts. The number of cancers observed was determined for each cancer type. The expected number of malignancies was ascertained from general population data. The parameter of interest was the standardised incidence ratio (SIR), the ratio of observed to expected malignancies.
The five studies included 47,325 SLE patients (42,171 females) observed for 282,553 patient years. There were 376 breast cancers, 66 endometrial cancers, and 44 ovarian cancers. The total number of cancers observed was less than that expected, with SIRs of 0.76 (95% CI: 0.69, 0.85) for breast cancer, 0.71 (95% CI: 0.55, 0.91) for endometrial cancer, and 0.66 (95% CI: 0.49, 0.90) for ovarian cancer.
Data strongly support a decreased risk of breast, ovarian, and endometrial cancers in SLE. This may be due to inherent differences in women in SLE (vs the general population) regarding endogenous oestrogen, other medications, and/or genetic make-up.
Prostate cancer in systemic lupus erythematosus Bernatsky, S.; Ramsey‐Goldman, R.; Gordon, C. ...
International journal of cancer,
15 December 2011, Letnik:
129, Številka:
12
Journal Article
Recenzirano
Odprti dostop
Our research objective was to estimate prostate cancer risk in systemic lupus erythematosus (SLE), relative to the age‐matched general population. A progressive literature review was performed to ...identify SLE cohort studies with cancer registry linkage for cancer ascertainment. Data were pooled from four studies of large SLE cohorts who met these criteria. The total number of prostate cancers observed was derived by pooling the incident cases across all studies. The total expected number of prostate, derived from applying appropriate general population cancer incidence data to the observed number of patient‐years of follow‐up for each study, was similarly determined. The parameter of interest was the standardized incidence ratio (SIR), the ratio of observed to expected malignancies. The four studies together provided a pool of 6,068 male SLE patients observed for a total of 38,186 patient‐years (mean 6.3 years). Within these subjects, 80 prostate cancers were observed. In each contributing study, the number of cancers expected far exceeded that observed. The pooled SIR estimate for prostate cancer risk in males with SLE, compared to the general population, was 0.72 (95% CI 0.57, 0.89). These data suggest a decreased risk of prostate cancer in SLE; more definite conclusions require additional data. As alterations in androgen pathways can potentially alter prostate risk, a lower risk of prostate cancer in SLE could possibly be due to low hypoadrenergic states which some believe may occur in men with SLE; underlying genetic factors could also be at play. Further study of these issues in large cohorts is needed.
To determine the frequency, accrual, attribution and outcome of neuropsychiatric (NP) events and impact on quality of life over 3 years in a large inception cohort of patients with systemic lupus ...erythematosus (SLE).
The study was conducted by the Systemic Lupus International Collaborating Clinics. Patients were enrolled within 15 months of SLE diagnosis. NP events were identified using the American College of Rheumatology case definitions, and decision rules were derived to determine the proportion of NP disease attributable to SLE. The outcome of NP events was recorded and patient-perceived impact determined by the SF-36.
1206 patients (89.6% female) with a mean (+/-SD) age of 34.5+/-13.2 years were included in the study. The mean disease duration at enrollment was 5.4+/-4.2 months. Over a mean follow-up of 1.9+/-1.2 years, 486/1206 (40.3%) patients had > or =1 NP events, which were attributed to SLE in 13.0-23.6% of patients using two a priori decision rules. The frequency of individual NP events varied from 47.1% (headache) to 0% (myasthenia gravis). The outcome was significantly better for those NP events attributed to SLE, especially if they occurred within 1.5 years of the diagnosis of SLE. Patients with NP events, regardless of attribution, had significantly lower summary scores for both mental and physical health over the study.
NP events in patients with SLE are of variable frequency, most commonly present early in the disease course and adversely impact patients' quality of life over time. Events attributed to non-SLE causes are more common than those due to SLE, although the latter have a more favourable outcome.
Objective
The Medical Outcomes Study Short Form 36 (SF‐36) is recommended to assess quality of life (QOL) in systemic lupus erythematosus (SLE). The aim of the current study was to assess QOL over ...time in the first 5 years of a multicenter inception cohort of patients with SLE.
Methods
An inception SLE cohort was assembled according to a standardized protocol between 2000 and 2012. In addition to clinical and laboratory assessments, patients completed the SF‐36 at yearly intervals. Only patients who had ≥5 completed QOL questionnaires were included in these analyses. Generalized estimating equation models were run separately for each of the 8 subscales and for the physical and mental component summary scores, adjusting for repeated measures by patients.
Results
A total of 495 patients were included. The mean ± SD disease duration at the first visit was 5.3 ± 4.1 months. The mean ± SD age at enrollment was 35.8 ± 13.2 years. All 8 subscales and the 2 summary scores showed improvement in the first 2 years from enrollment. Between years 2 and 5, none of the subscales or summary scores showed any change. Minimum clinically important improvement was achieved by 35–56% of the patients and was influenced by demographic and disease factors.
Conclusion
Unlike late‐stage lupus, where QOL is stable over time, in patients with early disease, all subscales improve in early followup up to 2 years. Therefore, the SF‐36 may be a sensitive outcome measure in early disease in patients with SLE.
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