Professional Documents
Culture Documents
Acr 22591
Acr 22591
ORIGINAL ARTICLE
Objective. Management of systemic lupus erythematosus (SLE) is complex and variability in practices exists. Guide-
lines have been developed to help improve the management of SLE patients, but there has been no formal evaluation
of these guidelines. This study aims to compare the scope, quality, and consistency of clinical practice guidelines on
the diagnosis, monitoring, and treatment of patients with SLE.
Methods. Electronic databases were searched up to April 2014. The Appraisal of Guidelines for Research and Evalua-
tion (AGREE) II instrument and textual synthesis was used to appraise and compare recommendations.
Results. Nine clinical practice guidelines and 5 consensus statements were identified, which covered 7 topics: diagno-
sis, monitoring, treatment, neuropsychiatric SLE, lupus nephritis, antiphospholipid syndrome, and other manifesta-
tions of lupus. The methodological quality of the guidelines was variable, with the overall mean AGREE II scores
ranging from 31% to 75%, out of a maximum 100%. Scores were consistently low for applicability, with only 1 guide-
line scoring above 50%. There was substantial variability in the treatments recommended for class II and V lupus
nephritis, the recommended duration of maintenance therapy for class III/IV lupus nephritis (from 1 to 4 years), and
timing of ophthalmologic examination for patients taking corticosteroids.
Conclusion. Published guidelines on SLE cover a complex area of clinical care, but the methodological quality, scope,
and recommendations varied substantially. Collaborative and multidisciplinary efforts to develop comprehensive, high-
quality evidence-based guidelines are needed to promote best treatment and health outcomes for patients with SLE.
1440
SLE Treatment Guidelines 1441
Figure 1. Search results. * 5 other guideline organizations, i.e., SIGN, NICE and professional rheumatology and nephrology society
websites; SLE 5 systemic lupus erythematosus.
1442 Tunnicliffe et al
(i.e., 2). The minimum possible score 5 the lowest possi- Monitoring. Six guidelines provided recommendations
ble score (i.e., 1) 3 number of items 3 number of apprais- on monitoring disease activity, disease damage, and quali-
ers (i.e., 2). ty of life (1015).
Measuring disease activity with full blood count, serum
Synthesis of guideline recommendations. Textual de- creatinine, urinalysis (1012), and other tests, including
scriptive synthesis was performed to analyze the scope C3/C4, antidouble-stranded DNA (anti-dsDNA), anti-
(the topics covered by the guidelines), content, and con- phospholipid, anti-RO/SSA, C-reactive protein, anti-C1q,
sistency of recommendations across the guidelines. All serum albumin, estimated glomerular filtration rate
text from guidelines was imported into HyperRESEARCH (eGFR), and urinary protein:creatinine ratio, were recom-
software for managing and retrieving textual data. One mended (12,13). The Systemic Lupus Erythrematosus Dis-
author (DJT) inductively identified topics addressed by ease Activity Index was the only tool specified for adults
the guidelines and coded the guideline recommendations (13) and adolescents (15).
into the corresponding topic. For each topic, the guideline Annual assessment of organ damage was recommended
recommendations were compared to identify similarities (11,13,15). The Systemic Lupus International Collaborat-
and differences. ing Clinics/ACR Damage Index was specified for use in
both the adult (13) and pediatric (15) populations.
Quality of life monitoring by clinical interview and/or
RESULTS visual analog scale (11) or Pediatric Quality of Life Inven-
tory Generic Core Scale, version 4.0, were suggested (15).
Search and guideline characteristics. The search Monitoring of drug toxicity was mentioned but no
yielded 2,399 citations. Fourteen were eligible and includ- thresholds were provided (10,11). The National Cancer
ed 9 clinical practice guidelines and 5 consensus state- Institutes Common Terminology Criteria for Adverse
ments (Figure 1). The articles were published between
Events, version 3.0, was recommended for use to monitor
1999 and 2014, 9 from international groups and 5 from
treatment side effects in pediatric SLE (15).
national groups. Eight guidelines were published by rheu-
Long-term monitoring was recommended (10,14), with
matology societies or working groups, 1 guideline was
36 month assessment for mild disease and increased
published by a nephrology guideline organization, and 5
frequency for patients with severe active disease and in
guidelines were published by multidisciplinary working
pregnancy (10). Patients with nonactive SLE and no dam-
groups. The characteristics of the guidelines are provided
age or comorbidity could be assessed every 6 to12 months
in Table 1. Four guidelines (29%) conducted external peer
with additional evaluation prior to pregnancy, surgery,
review and 11 guidelines (79%) included a systematic lit-
transplantation, use of estrogen-containing medication, or
erature review, although the methods of data extraction
occurrence of a new neurologic or vascular event (11).
and synthesis varied (see Supplementary Table 2, avail-
Recommendations for monitoring comorbidities were
able in the online version of this article at http://onlinelibrary.
presented in 3 guidelines (11,12,16). European League
wiley.com/doi/10.1002/acr.22591/abstract).
Against Rheumatism (EULAR) 2010 guidelines stated that
Methodological quality. Table 2 provides a summary of all patients with SLE should be assessed for adequate cal-
the results of the methodological quality appraisal. The cium intake, vitamin D intake, regular exercise, smoking
domain scores of each guideline are displayed in Supple- status, cardiovascular risk factors, blood cholesterol,
mentary Table 3 (available in the online version of this glucose, body mass index, and blood pressure with no
article at http://onlinelibrary.wiley.com/doi/10.1002/acr. specific parameters provided (11). Ophthalmologic exami-
22591/abstract). The highest scoring domain was scope nation for patients taking antimalarial medication varied;
and purpose at 67% (4489%), and the lowest scoring 1 guideline recommended an annual review (16) and
domain was applicability at 29% (467%). another a 5-year review (11) (Table 3).
The ACR 1999 guideline advocated multidisciplinary
Descriptive synthesis. The 7 topics addressed by the monitoring of SLE, involving collaboration among prima-
guidelines were diagnosis, monitoring, treatment, neuro- ry care physicians, specialists, nurses, pharmacists, fami-
psychiatric SLE, lupus nephritis, anti-phospholipid syn- lies, and patients (10).
drome, and other organ manifestations. The scope of the
guidelines varied considerably (Supplementary Tables 4 Treatment. Treatment was covered by 5 guidelines.
and 5, available in the online version of this article at Recommendations focused on ensuring long-term surviv-
http://onlinelibrary.wiley.com/doi/10.1002/acr.22591/abstract). al, preventing organ damage, and improving quality of life
by controlling disease activity and minimizing comorbid-
Diagnosis. The American College of Rheumatology ities and drug toxicity (14). Treatment targets for SLE were
(ACR) criteria for classification of patients with SLE (9) defined as remission and prevention of flares (14), with
are widely used as a diagnostic aid. In patients with 4 of goals defined through a shared decision-making process
the 11 criteria, the diagnosis of SLE can be made with between the patient and clinician (14,17).
95% specificity and 85% sensitivity (9). One guideline Recommended treatment for constitutional SLE includ-
specifically stated that SLE should be suspected in any ed antimalarial drugs (10,12,14), corticosteroids, and non-
patient with features affecting 2 or more organ systems steroidal antiinflammatory drugs (10,12). Appropriate
listed in the ACR criteria (10). adjunct therapy included vitamin D and calcium supple-
Table 1. Characteristics of included guidelines*
Guideline Grade
organization/ Guideline Publication Target Work group Guideline Methods Evidence Level of of
society (ref.) name(s) year users specialties review support base evidence rec.
EULAR (12) EULAR 2008 Not stated Rheumatology, Review Editorial Systematic 1 1
recommendations immunology, (unclear team review
for the nephrology, if external) and expert
management of epidemiology opinion
SLE
SLE Treatment Guidelines
EULAR (18) EULAR 2010 Not clear Rheumatology, External Editorial Systematic 1 1
recommendations neurology, peer team review
for the radiology, review
management of immunology,
neuropsychiatric nephrology,
SLE epidemiology
EULAR (11) EULAR 2010 Not clear Rheumatology, External Editorial Systematic 1 1
recommendations general med, peer team review
for monitoring dermatology, review
patients with SLE nephrology,
immunology
EULAR/ERA- EULAR/ERA-EDTA 2012 Not clear Rheumatology, External Editorial Systematic 1 1
EDTA (19) recommendations nephrology, peer team review
for the pathology, review
management of general medi-
lupus nephritis cine, neurology
ACR (10) Guidelines for 1999 Primary care Rheumatology Reviewed Not stated Available
referral and physicians by primary evidence
management of care and expert
SLE in adults physicians opinion
ACR (20) ACR guidelines for 2012 Physicians Rheumatology, Internal Working Systematic 1
screening, managing nephrology review group review
treatment and man- lupus and expert
agement of lupus nephritis opinion
nephritis patients
KDIGO (22) KDIGO guideline for 2012 Nephrologists Nephrology External Evidence Systematic 1 1
glomerulonephritis peer review review
(chap. 12, lupus review team
nephritis)
SER (13) SER consensus 2013 Clinicians Rheumatology Not stated SER research Systematic 1 1
statement on the involved unit review
use of biologic in treatment
therapy for SLE of SLE
patients
SEMI and Diagnosis and 2012 Not clear Rheumatology, Not stated Not stated Systematic 1 1
SEN (16) treatment of lupus nephrology review
nephritis; and expert
consensus opinion
document
1443
(continued)
1444
Table 1. (Contd)
Guideline Grade
organization/ Guideline Publication Target Work group Guideline Methods Evidence Level of of
society (ref.) name(s) year users specialties review support base evidence rec.
Dutch Working Dutch guidelines 2012 Not clear Rheumatology, Not stated Not stated Systematic 1
Group for diagnosis and nephrology, review
on SLE (21) therapy of immunology and expert
proliferative opinion
lupus nephritis
Working group of Off-label therapeutic 2012 Clinicians involved Rheumatology Not stated Not stated Systematic 1
experts on options for SLE. in treatment of review
SLE (17) difficult SLE and expert
opinion
T2T International Treat-to-target 2014 Those involved in Rheumatology, External Not stated Systematic 1 1
Task Force (14) in SLE: care of patients nephrology, peer review
recommendations with SLE immunology, review and expert
from an dermatology, opinion
international internal medi-
task force cine, patient
representative
ALNN (23) Lupus nephritis 2013 Not clear Rheumatology, Not stated Not stated Available 1 1
management nephrology evidence
guidelines, and expert
perspective from opinion
Asia
CARRA (15) Consensus treatment 2012 Pediatric Rheumatology Not stated Not stated Systematic 1
plans for induction rheumatologists review
therapy of and expert
proliferative lupus opinion
nephritis in
juvenile SLE
* 1 5 used in guideline recommendations; 5 not used in guideline recommendations; rec. 5 recommendation; EULAR 5 European League Against Rheumatism; SLE 5 systemic lupus erythemato-
sus; ERA 5 European Renal Association; EDTA 5 European Dialysis and Transplant Association; ACR 5 American College of Rheumatology; KDIGO 5 Kidney Disease Improving Global Outcomes; SER 5
Spanish Society of Rheumatology; SEMI 5 Spanish Society of Internal Medicine; SEN 5 Spanish Society of Nephrology; T2T 5 treat-to-target; ALNN 5 Asian Lupus Nephritis Network; CARRA 5
Childhood Arthritis and Rheumatology Research Alliance.
Detailed explanation of level of evidence and grade of recommendation in Supplementary Table 2, available in the online version of this article at http://onlinelibrary.wiley.com/doi/10.1002/acr.
22591/abstract.
Regarding available evidence, it is unclear if systematic review was completed.
ALLN 2013 guidelines also published in Mok, CC, Yap DY, Navara SV, Liu ZH, Zhao MH, Lu L, et al. Overview of lupus nephritis management guidelines and perspective from Asia. Nephrology
2014;19:1120.
Tunnicliffe et al
SLE Treatment Guidelines 1445
* 5 recommended without dosage/criteria; 5 recommended; 5 no recommendation; EULAR 5 European League Against Rheumatism; ERA 5 European Renal Association; EDTA 5 European
Dialysis and Transplant Association; ACR 5 American College of Rheumatology; KDIGO 5 Kidney Disease Improving Global Outcomes; SEMI 5 Spanish Society of Internal Medicine; SEN 5 Spanish
Society of Nephrology; ISN/RPS 5 International Society of Nephrology/Renal Pathology Society; BMI 5 body mass index; eGFR 5 estimated glomerular filtration rate; anti-dsDNA 5 antidouble-
stranded DNA.
Tunnicliffe et al
Table 4. Guideline recommendations for treatment of lupus nephritis*
Guideline treatment EULAR EULAR/ ACR KDIGO SEMI and Dutch Aringer ALNN CARRA
recommendations (11,12) ERA-EDTA (19) (10,20) (22) SEN (16) group (21) et al (17) (23) (15)
Guideline treatment EULAR EULAR/ ACR KDIGO SEMI and Dutch Aringer ALNN CARRA
recommendations (11,12) ERA-EDTA (19) (10,20) (22) SEN (16) group (21) et al (17) (23) (15)
* 5 recommended without dosage/criteria; 5 recommended; 5 no recommendation; EULAR 5 European League Against Rheumatism; ERA 5 European Renal Association; EDTA 5 European
Dialysis and Transplant Association; ACR 5 American College of Rheumatology; KDIGO 5 Kidney Disease Improving Global Outcomes; SEMI 5 Spanish Society of Internal Medicine; SEN 5 Spanish
Society of Nephrology; ALNN 5 Asian Lupus Nephritis Network; CARRA 5 Childhood Arthritis and Rheumatology Research Alliance; CS 5 corticosteroid; AZA 5 azathioprine; MMF 5 mycopheno-
late mofetil; CNI 5 calcineurin inhibitors; MPD 5 methylprednisolone; IV 5 intravenous; CYC = cyclophosphamide; MPA 5 mycophenolic acid/sodium; CKD 5 chronic kidney disease; GFR 5 glo-
merular filtration rate; RRT 5 renal replacement therapy; TNF 5 tumor necrosis factor.
ALNN recommendations are for adult Asian lupus nephritis patients.
CARRA recommendations on pediatric lupus nephritis.
0.8 mg/kg/day prednisone when not used with IV MPD.
See reference 15 for CS dosages; CS regimen can be primarily oral, primarily IV, or mixed oral/IV.
# Euro lupus IV CYC dose 0.5 gm/m2 every 2 weeks for a total of 6 doses (3 months); NIH IV CYC dose 0.51 gm/m2 monthly for 6 months.
Tunnicliffe et al
SLE Treatment Guidelines 1449
EULAR/
EULAR ERA-EDTA ACR KDIGO SEMI and Dutch CARRA
Guideline recommendations (11,12) (19) (10,20) (22) SEN (16) group (21) (15)
* 5 recommended; 5 no recommendation; EULAR 5 European League Against Rheumatism; ERA 5 European Renal Association; EDTA = Euro-
pean Dialysis and Transplant Association; ACR 5 American College of Rheumatology; KDIGO 5 Kidney Disease Improving Global Outcomes;
SEMI 5 Spanish Society of Internal Medicine; SEN 5 Spanish Society of Nephrology; CARRA 5 Childhood Arthritis and Rheumatology Research
Alliance; MMF 5 mycophenolate mofetil; MPA 5 mycophenolic acid/sodium; CYC 5 cyclophosphamide; ESKD 5 end-stage kidney disease;
CS 5 corticosteroid; AZA 5 azathioprine; CNI 5 calcineurin inhibitors; ACE 5 angiotensin-converting enzyme; ARB 5 angiotensin II receptor
blocker.
CARRA recommendations on pediatric lupus nephritis.
management (19,22), with drug doses based on patient of SLE (13,16,22). Lupus arthritis standard of care includ-
size and GFR (22). Coordinated transition from pediatric ed corticosteroids, antimalarial drugs, azathioprine, and
to adult care was recommended (19). One guideline dis- methotrexate (13,17). For refractory disease, mycopheno-
cussed induction therapy for proliferative lupus nephritis, late mofetil as well as rituximab were suggested (13,17).
with in-depth corticosteroid and immunosuppressant reg- Antiinterleukin 1 and antitumor necrosis factor antago-
imens provided; drug toxicity thresholds and monitoring nists were not recommended in these patients (17).
tests for mycophenolate mofetil and mycophenolate sodi- The standard of care for hematologic manifestations of
um/acid were also provided (15). SLE included corticosteroids and azathioprine, mycophe-
nolate, or cyclophosphamide (17), with rituximab in re-
Antiphospholipid syndrome. The therapeutic goal was fractory disease (13,17). Plasma exchange (18,23) or
prevention of thromboembolic events (14,17). Low-dose immunoadsorption were mentioned (17), as was splenec-
aspirin was recommended as primary prevention for tomy in disease refractory to drug therapy (17).
thrombosis (12,19), preeclampsia and pregnancy loss
(12,19,21,22), and associated nephropathy (19,21), while
in nephropathy antimalarial and/or antiplatelet/anticoa- DISCUSSION
gulation therapy could be considered (19), with an inter- The variability in published guidelines for SLE was sub-
national normalized ratio of 23 (22). stantial, particularly in terms of scope and methodological
Long-term anticoagulation for secondary prevention of rigor. Many recommendations were consistent, but major
recurrent stroke (19) or thrombosis was recommended discrepancies were observed for specific clinical situa-
(12,16). Intensive immunomodulatory therapy (high-dose tions, particularly proteinuria thresholds indicating renal
glucocorticoids, IV immunoglobulins, plasmapheresis) or biopsy, treatment of class II and V nephritis, and duration
B cell depletion (rituximab or apheresis) were suggested of maintenance therapy.
for catastrophic antiphospholipid syndrome (17). Guideline scope varied broadly, ranging from the com-
plete management of SLE to off-label medication use. The
Other manifestations of SLE. Three guidelines provid- majority of guidelines were focused on lupus nephritis,
ed recommendations regarding other organ manifestations and we speculated that this may be due to the larger body
1450 Tunnicliffe et al
of research evidence on the treatment of lupus nephritis dence and were therefore based on expert opinion and
compared with other areas of SLE. Also, scope may have consensus (e.g., treatment of class II and V lupus nephri-
varied due to resource availability. For example, the scope tis). A challenge in developing high-quality guidelines on
of the guideline may have been narrowed to ensure the SLE is the lack of high-quality evidence for almost all
feasibility of developing high quality guidelines. Diagno- aspects of disease except lupus nephritis. Therefore, as
sis of SLE was sparsely covered by guidelines and perhaps recommended by the Grading of Recommendations As-
this is because it remains a challenging area due to the sessment, Development and Evaluation Working Group
wide differential diagnoses, lack of evidence on the signs, (GRADE) (40), suggestions for clinical care may be based
symptoms, and biomarkers for SLE and a lack of consen- on expert opinion, although the level of evidence must be
sus (2426). Guidelines rarely discussed the treatment explicit. In some areas, evidence was not included in
goals of complete and/or partial remission, which are fre- guideline recommendations, e.g., IV cyclophosphamide
quently reported in randomized control trials of treatment use in induction therapy. A recent Cochrane review sup-
for lupus nephritis, despite there being no standardized ports the recommendations of major lupus nephritis
criteria (27). guidelines (19,20,22), i.e., the use of either mycophenolate
Although most guideline recommendations were mofetil or low-dose cyclophosphamide in induction thera-
formed on the basis of a systematic literature review, there py of class III or IV lupus nephritis. However, the review
were important differences in the approach to evidence suggests that mycophenolate mofetil may be a preferred
appraisal and grading of recommendations. Guideline first-line agent due to an overall better adverse effect pro-
applicability was generally poor using the AGREE II file compared to low-dose cyclophosphamide (41,42).
instrument. For example, the target clinical context and Two guidelines were published after this review (14,23),
patient population were often not specified. Also, poten- but specific therapies for lupus nephritis induction were
tial barriers to guideline implementation were not identi- not covered by one (14), while the other recommended
fied in most guidelines. To assess barriers, we suggest corticosteroid and either mycophenolate mofetil or cyclo-
using the National Institute for Clinical Studies barrier
phosphamide induction therapy (23).
tool (28) or Barriers Identification and Mitigation tool (29).
Some important areas of treatment, such as nonadher-
Furthermore, criteria and frequency for auditing should
ence, were not covered in guidelines. Rates of nonadher-
be provided; for example, lupus nephritis guidelines
ence in SLE have been reported as high as 76% (43) and
could suggest collecting data on the indication for renal
are associated with a higher risk of flare, morbidity, hospi-
biopsy for on-going audit. While recommendations for
talization, and poor renal outcome (44). Nonadherence to
audit were not included in many of the guidelines, we rec-
therapy as a cause of treatment failure is commonly seen
ognize that professional societies, including the ACR,
in clinical practice (28) and may affect therapeutic deci-
have developed quality measures for the purposes of audit
sions. Addressing the issue of adherence is likely to be an
and performance measurement, as separate initiatives sub-
important part of optimizing outcomes. A number of trials
sequent to guideline development (3032). Well-designed,
are underway examining a way of measuring adherence
focused guideline implementation projects with active
involvement from guideline organizations are widely that will help inform future guidelines (45), while further
advocated (33). Mold et al (34) explored adherence to studies are required to identify appropriate interventions
national guidelines on asthma using multifaceted inter- for adherence in chronic disease (46).
ventions in a cluster randomized trial, which showed This study is the first to systematically review the quali-
facilitation of the guideline by an independent source ty of clinical practice guidelines on SLE diagnosis, moni-
improved adherence to recommendations compared to toring, and treatment. However, our study has limitations.
passive facilitation, by the provision of education and per- The assessment of the guidelines is based on the reporting
formance feedback alone (34). by guideline developers and ignores that the ACR recently
Improving guideline applicability could also be achieved decided to use GRADE methodology in all future guide-
by the active involvement of patient and caregivers in their lines, while the exclusion of non-English guidelines may
development, which has been widely advocated (3537), limit the generalizability of the findings to other settings.
yet only 1 guideline addressed stakeholder involvement by Overall there is significant variability in existing guide-
specifically involving patients in guideline development. lines for the management of SLE. Some of the variation is
Active consumer engagement can be facilitated by involving explained by the paucity of evidence in areas such as bio-
more than 1 consumer in working groups or conducting markers, signs and symptoms for the monitoring and diag-
stakeholder input exercises to elicit consumers preferences nosis of SLE, studies to identify the lowest safe dose of
and priorities (38); this has been successfully conducted for corticosteroids, and the duration of maintenance therapy
developing guidelines addressing other specialties, includ- for patients with nephritis. Furthermore, evidence-based
ing chronic kidney disease (39). criteria for diagnosis, SLE flare, and SLE remission need
The recommendations on the diagnosis, monitoring, to be better defined and means of monitoring adherence
and treatment for lupus nephritis varied across guidelines would be a beneficial addition to guidelines.
and this could be due to the different populations includ- Clearly a great deal of work has been done in developing
ed. For example, one guideline focused on the treatment the identified guidelines, but to avoid duplication of effort
of pediatric patients (15), and another guideline focused in the future we recommend that international collabora-
on treatment of adult Asian patients (23). These discrep- tive multidisciplinary efforts are undertaken to ensure the
ancies were more apparent in areas with low-quality evi- development of comprehensive, high-quality evidence-
SLE Treatment Guidelines 1451
based guidelines to improve the treatment and health of 14. Van Vollenhoven RF, Mosca M, Bertsias G, Isenberg D,
patients with SLE. Kuhn A, Lerstrom K, et al. Treat-to-target in systemic lupus
erythematosus: recommendations from an international task
force. Ann Rheum Dis 2014;73:95867.
15. Mina R, von Scheven E, Ardoin SP, Eberhard BA, Punaro
AUTHOR CONTRIBUTIONS M, Ilowite N, et al. Consensus treatment plans for induction
therapy of newly diagnosed proliferative lupus nephritis in
All authors were involved in drafting the article or revising it crit- juvenile systemic lupus erythematosus. Arthritis Care Res
ically for important intellectual content, and all authors approved (Hoboken) 2012;64:37583.
the final version to be submitted for publication. Mr. Tunnicliffe 16. Ruiz IG, Espinosa G, Frutos M, Jimenez AJ, Praga M,
had full access to all of the data in the study and takes responsibility Pallares L, et al. Diagnosis and treatment of lupus nephritis:
for the integrity of the data and the accuracy of the data analysis. consensus document from the systemic auto-immune dis-
Study conception and design. Tunnicliffe, Singh-Grewal, Craig, ease group (GEAS) of the Spanish Society of Internal Medi-
Tong. cine (SEMI) and Spanish Society of Nephrology (SEN).
Acquisition of data. Tunnicliffe, Kim, Tong. Nefrologia 2012;32:135.
Analysis and interpretation of data. Tunnicliffe, Singh-Grewal, 17. Aringer M, Burkhardt H, Burmester GR, Fischer-Betz R,
Kim, Craig, Tong. Fleck M, Graninger W, et al. Current state of evidence on
off label therapeutic options for systemic lupus erythema-
tosus, including biological immunosuppressive agents, in
Germany, Austria, and Switzerland: a consensus report.
REFERENCES Lupus 2012;21:386401.
18. Bertsias GK, Ioannidis JP, Aringer M, Bollen E, Bombardieri
1. Bernatsky S, Boivin JF, Joseph L, Manzi S, Ginzler E,
S, Bruce IN, et al. EULAR recommendations for the manage-
Gladman DD, et al. Mortality in systemic lupus erythemato-
ment of systemic lupus erythematosus with neuropsychiat-
sus. Arthritis Rheum 2006;54:25507.
ric manifestations: report of a task force of the EULAR
2. Lerang K, Gilboe IM, Gran JT. Differences between rheuma-
standing committee for clinical affairs. Ann Rheum Dis
tologists and other internists regarding diagnosis and treat-
2010;69:207482.
ment of systemic lupus erythematosus. Rheumatology
19. Bertsias GK, Tektonidou M, Amoura Z, Aringer M, Bajema
(Oxford) 2012;51:6639.
I, Berden JH, et al. Joint European League Against Rheuma-
3. Walsh M, Jayne D, Moist L, Tonelli M, Pannu N, Manns B.
tism and European Renal Association-European Dialysis
Practice pattern variation in oral glucocorticoid therapy after
and Transplant Association (EULAR/ERA-EDTA) recom-
the induction of response in proliferative lupus nephritis. mendations for the management of adult and paediatric
Lupus 2010;19:62833. lupus nephritis. Ann Rheum Dis 2012;71:177182.
4. Siedner MJ, Christopher-Stine L, Astor BC, Gelber AC, Fine 20. Hahn BH, McMahon MA, Wilkinson A, Wallace WD, Daikh DI,
DM. Screening for proteinuria in patients with lupus: a sur- FitzGerald JD, et al. American College of Rheumatology guide-
vey of practice preferences among American rheumatolo- lines for screening, treatment, and management of lupus
gists. J Rheumatol 2007;34:9737. nephritis. Arthritis Care Res (Hoboken) 2012;64:797808.
5. Brunner H, Klein-Gitelman M, Ying J, Tucker L, Silverman 21. Van Tellingen A, Voskuyl A, Vervloet M, Bijl M, de Sevaux R,
E. Corticosteroid use in childhood-onset systemic lupus Berger S, et al. Dutch guidelines for diagnosis and therapy of
erythematosus-practice patterns at four pediatric rheumatol- proliferative lupus nephritis. Neth J Med 2012;70:199207.
ogy centers. Clin Exp Rheumatol 2009;27:15562. 22. Kidney Disease Improving Global Outcomes Work Group.
6. Grimshaw J, Russell I. Achieving health gain through clini- KDIGO clinical practice guideline for glomerulonephritis.
cal guidelines. I: developing scientifically valid guidelines. Kidney Int Suppl 2012;2:139274. URL: http://www.kdigo.
Qual Health Care 1993;2:2438. org/clinical_practice_guidelines/pdf/KDIGO-GN-Guideline.pdf.
7. Grimshaw JM, Russell IT. Effect of clinical guidelines on 23. Mok CC, Yap DY, Navarra SV, Liu Zh, Zhao Mh, Lu L, et al.
medical practice: a systematic review of rigorous evalua- Overview of lupus nephritis management guidelines and
tions. Lancet 1993;342:131722. perspective from Asia. Int J Rheum Dis 2013;16:62536.
8. Brouwers MC, Kho ME, Browman GP, Burgers JS, Cluzeau 24. Bertsias GK, Pamfil C, Fanouriakis A, Boumpas DT. Diag-
F, Feder G, et al. AGREE II: advancing guideline develop- nostic criteria for systemic lupus erythematosus: has the
ment, reporting and evaluation in health care. CMAJ 2010; time come? Nat Rev Rheumatol 2013;9:68794.
182:E839E42. 25. Doria A, Zen M, Canova M, Bettio S, Bassi N, Nalotto L,
9. Hochberg MC, for the Diagnostic and Therapeutic Criteria et al. SLE diagnosis and treatment: when early is early.
Committee of the American College of Rheumatology. Autoimmun Rev 2010;10:5560.
Updating the American College of Rheumatology revised 26. Yu C, Gershwin ME, Chang C. Diagnostic criteria for sys-
criteria for the classification of systemic lupus erythemato- temic lupus erythematosus: a critical review. J Autoimmun
sus [letter]. Arthritis Rheum 1997;40:1725. 2014;48:103.
10. American College of Rheumatology Ad Hoc Committee on 27. Boumpas D, Balow J. Outcome criteria for lupus nephritis
Systemic Lupus Erythematosus Guidelines. Guidelines for trials: a critical overview. Lupus 1998;7:6229.
referral and management of systemic lupus erythematosus 28. Bose B, Silverman ED, Bargman JM. Ten common mistakes
in adults. Arthritis Rheum 1999;42:178596. in the management of lupus nephritis. Am J Kidney Dis
11. Mosca M, Tani C, Aringer M, Bombardieri S, Boumpas D, 2014;63:66776.
Brey R, et al. European League Against Rheumatism recom- 29. Gurses AP, Murphy DJ, Martinez EA, Berenholtz SM,
mendations for monitoring patients with systemic lupus Pronovost PJ. A practical tool to identify and eliminate bar-
erythematosus in clinical practice and in observational stud- riers to compliance with evidence-based guidelines. Jt
ies. Ann Rheum Dis 2010;69:126974. Comm J Qual Patient Saf 2009;35:52632.
12. Bertsias G, Ioannidis JP, Boletis J, Bombardieri S, Cervera R, 30. Saag KG, Yazdany J, Alexander C, Caplan L, Coblyn J, Desai
Dostal C, et al. EULAR recommendations for the management SP, et al. for the American College of Rheumatology Quality
of systemic lupus erythematosus: report of a task force of the Measurement White Paper Development Work Group. Defin-
EULAR Standing Committee for international clinical studies ing quality of care in rheumatology: the American College
including therapeutics. Ann Rheum Dis 2008;67:195205. of Rheumatology white paper on quality measurement.
13. Calvo-Alen J, Silva-Fernandez L, Ucar-Angulo E, Pego- Arthritis Care Res (Hoboken) 2011;63:29.
Reigosa JM, Olive A, Martinez-Fernandez C, et al. SER con- 31. Dougados M, Betteridge N, Burmester G, Euller-Ziegler L,
sensus statement on the use of biologic therapy for systemic Guillemin F, Hirvonen J, et al. EULAR standardised operating
lupus erythematosus. Reumatologa Clnica 2013;09:28196. procedures for the elaboration, evaluation, dissemination, and
1452 Tunnicliffe et al
implementation of recommendations endorsed by the EULAR 39. Tong A, Lopez-Vargas P, Howell M, Phoon R, Johnson D,
standing committees. Ann Rheum Dis 2004;63:11726. Campbell D, et al. Consumer involvement in topic and out-
32. Van der Heijde D, Aletaha D, Carmona L, Edwards CJ, come selection in the development of clinical practice
Kvien TK, Kouloumas M, et al. 2014 update of the EULAR guidelines. Health Expect 2012;15:41023.
standardised operating procedures for EULAR-endorsed rec- 40. Balshem H, Helfand M, Schunemann HJ, Oxman AD, Kunz
ommendations. Ann Rheum Dis 2015;74:813. R, Brozek J, et al. GRADE guidelines: 3. Rating the quality
33. Grol R. Successes and failures in the implementation of of evidence. J Clin Epidemiol 2011;64:4016.
evidence-based guidelines for clinical practice. Med Care 41. Henderson L, Masson P, Craig JC, Flanc RS, Roberts MA,
2001;39: Suppl 2:II4654. Strippoli FM, et al. Treatment for lupus nephritis. Cochrane
34. Mold JW, Fox C, Wisniewski A, Lipman PD, Krauss MR, Database Syst Rev 2012;12;12:CD002922.
Harris DR, et al. Implementing asthma guidelines using 42. Henderson LK, Masson P, Craig JC, Roberts MA, Flanc RS,
practice facilitation and local learning collaboratives: a ran- Strippoli GF, et al. Induction and maintenance treatment of
domized controlled trial. Ann Fam Med 2014;12:23340. proliferative lupus nephritis: a meta-analysis of randomized
35. Krahn M, Naglie G. The next step in guideline development: controlled trials. Am J Kidney Dis 2013;61:7487.
incorporating patient preferences. JAMA 2008;300:4368. 43. Costedoat-Chalumeau N, Pouchot J, Guettrot-Imbert G, Le
36. Nilsen E, Myrhaug H, Johansen M, Oliver S, Oxman A. Guern V, Leroux G, Marra D, et al. Adherence to treatment
Methods of consumer involvement in developing healthcare in systemic lupus erythematosus patients. Best Pract Res
policy and research, clinical practice guidelines and patient Clin Rheumatol 2013;27:32940.
information material. Cochrane Database Syst Rev 2006;3: 44. Bruce IN, Gladman DD, Urowitz MB. Factors associated
CD004563. with refractory renal disease in patients with systemic lupus
37. Schunemann H, Fretheim A, Oxman AD. Improving the use erythematosus: the role of patient nonadherence. Arthritis
of research evidence in guideline development: 10. Integrat- Care Res 2000;13:4068.
ing values and consumer involvement. Health Res Policy 45. Costedoat-Chalumeau N. International prospective study on
Syst 2006;4:22. adherence to treatment in patients with active systemic lupus
38. Eccles MP, Grimshaw JM, Shekelle P, Schunemann HJ, erythematosus (TPASLE). 2011. URL: http://clinicaltrials.
Woolf S. Developing clinical practice guidelines: target gov/show/NCT01509989.
audiences, identifying topics for guidelines, guideline group 46. Nieuwlaat R, Wilczynski N, Navarro T, Hobson N, Jeffery R,
composition and functioning and conflicts of interest. Imp Keepanasseril A, et al. Interventions for enhancing medication
Sci 2012;7:60. adherence. Cochrane Database Syst Rev 2014;11:CD000011.