CME

Systemic lupus erythematosus:

An update on treat-to-target
Amy Lynn Roberts, PA-C; Denise Rizzolo, PA-C, PhD

ABSTRACT
Systemic lupus erythematosus involves many organ systems,
and its vague and multisystem manifestations make early
diagnosis and treatment difficult. However, early diagnosis
and treatment offer the best chance of reducing end-organ
damage and achieving remission. This article describes a
new strategy called treat-to-target that may help patients
achieve remission.
Keywords: systemic lupus erythematosus, treat-to-target, T2T,
autoimmune disease, cardiovascular disease, osteoporosis

Learning objectives
Explain the pathophysiology of lupus and clinical presenta-

© CHARLOTTA NORGAARD / PATIENTPROTOCOL.NET

tion of patients with this disease.
Discuss the diagnostic testing and previously established
treatment options for patients with lupus.
Describe the therapeutic strategy of treat-to-target for the
management and goal of remission of lupus.

S
ystemic
i llupus erythematosus
h iis a chronic
h i iinfl
flamma-
tory disease affecting multiple organ systems as a
result of immune system dysregulation, and can be
fatal. The cause of lupus is not fully understood but is
believed to be multifactorial.1 Early diagnosis and treat-
ment are important in preventing tissue and organ dam-
age and achieving remission. Reaching these goals can An emerging treatment concept, treat-to-target (T2T),
increase long-term patient survival and improve quality is being successfully applied to the treatment of rheumatoid
of life. The treatment of rheumatic disorders such as lupus arthritis (RA) as well as other chronic diseases.2-5 Previous
has been a struggle: because numerous organ systems are clinical trials that focused on RA demonstrated how T2T
involved, patients must take multiple medications. better supports disease control and remission.2-5 Due to
Although some treatments work well for certain symp- the success of this research, T2T is now being explored for
toms, they can worsen others, prompting the need for patients with lupus.
further intervention. In T2T, the patient and clinician mutually decide on an
attainable target or level of disease and use aggressive
Amy Lynn Roberts practices at the Sisselman Medical Group in treatments and modifications to reach the target.2,3,5 Each
Massapequa, N.Y., and is a recent graduate of the Pace Completion
patient’s target is individualized by their disease stage and
Program in New York City. Denise Rizzolo is an associate professor
in the PA program at Seton Hall University in South Orange, N.J., an severity. For some, the goal is to control pain or fatigue;
assistant clinical professor in the Pace completion program in New for others, the goal is to use the lowest possible cortico-
York City, and practices urgent care in Springfield, N.J. The authors steroid dose. The overall objective is remission. However,
have disclosed no potential conflicts of interest, financial or otherwise. this can be difficult due to lupus’ effect on multiple organ
DOI: 10.1097/01.JAA.0000470432.76823.93 systems and the obstacles clinicians commonly encounter
Copyright © 2015 American Academy of Physician Assistants when trying to make an early diagnosis. This article provides

22 www.JAAPA.com Volume 28 • Number 9 • September 2015

Copyright © 2015 American Academy of Physician Assistants

 Systemic lupus erythematosus: An update on treat-to-target

Key points TABLE 1. Drugs that may induce lupus

Systemic lupus erythematosus involves many organ Drugs capable of inducing lupus:
systems, and its vague and multisystem manifestations • Chlorpromazine
make early diagnosis and treatment difficult. • Hydralazine
Early diagnosis and treatment offer the best chance of • Isoniazid
reducing end-organ damage and achieving remission. • Methyldopa
T2T, which has been used in patients with diabetes, • Minocycline
hypertension, and rheumatoid arthritis, may help patients • Procainamide
with lupus achieve remission. • Quinidine

Drugs that possibly induce lupus:

• Anticonvulsants (carbamazepine, ethosuximide,
a brief update on lupus and describes the benefits and phenytoin, diphenylhydantoin, primidone, trimethadione,
challenges of using T2T. valproate, zonisamide)
• Antithyroid drugs (propylthiouracil, methimazole,
PATHOGENESIS thiamazole)
Lupus is caused by a culmination of factors, including sex, • Beta-blockers (acebutolol, labetalol, propranolol, pindolol,
age, ethnicity, and genetics.1 Environmental exposures such atenolol, metoprolol, timolol)
as ultraviolet light, medications (Table 1), and infectious • Fluorouracil agents (fluorouracil, tegafur, tegafur-uracil)
agents also are thought to have an association with lupus • Hydrochlorothiazide terbinafine
• Interferon
development.6,7
• Penicillamine
• Statins (lovastatin, simvastatin, fluvastatin)
EPIDEMIOLOGY
• Sulfasalazine
An estimated 51 per 100,000 people with lupus are living
in the United States, and 2 to 8 new cases per 100,000 Drugs suggested to induce lupus:
population are diagnosed each year in North America, • Calcium channel blockers
South America, and Europe.1,6 Lupus is most common in • Captopril
black, Hispanic, and Asian patients ages 15 to 44 years.1,6 • Ciprofloxacin
Research suggests lupus is 9 to 10 times more common in • Clonidine
women, which suggests that hormones may be a contrib- • Estrogens and oral contraceptives
• Gemfibrozil
uting factor in its development.1,6,8 Siblings of patients with
• Gold salts
lupus are 30 times more likely to develop the disease,
• Griseofulvin
confirming a genetic predisposition.6
• Hydroxyurea
In the 1950s, about half of patients with lupus were still • Interferons
alive 10 years after diagnosis; as of 2000, the 10-year • Lithium
survival rate was over 90%.5,9 The rise in survival rate • Para-aminosalicylic acid
could possibly be due to increased provider awareness, • Penicillin
leading to an earlier diagnosis and treatment. • Phenylbutazone
• Reserpine
DIAGNOSIS AND CLASSIFICATION • Rifampin
Before appropriate T2T goals can be established, lupus • Streptomycin
must be appropriately diagnosed using a combination of • Tetracycline
signs, symptoms, and laboratory studies. Because the
Drugs recently reported to induce lupus:
signs and symptoms of lupus are nonspecific, patients • Clobazam
typically seek medical attention from their primary care • Clozapine
provider first, so being able to recognize the vague signs • Etanercept
and symptoms and make a timely diagnosis is crucial. • Infliximab
Some of the elusive symptoms include malar or discoid • Interleukin-2
rash, photosensitive rash, oral ulcers, fever, hair loss, • Lisinopril
fatigue, anemia, leukopenia, and hematuria.8 Early rec- • Tocainide
ognition can reduce the patient’s risk for organ damage, • Zafirlukast.
prolong the time between relapses, and may reduce time
Adapted with permission from Antonov D, Kazandjieva J, Etugov D,
to remission. et al. Drug-induced lupus erythematosus. Clin Dermatol. 2004;22(2):
Criteria are available to help with classifying lupus, but 157-166.
are only intended for use in scientific research. A lupus

JAAPA Journal of the American Academy of Physician Assistants www.JAAPA.com 23

Copyright © 2015 American Academy of Physician Assistants

CME
diagnosis is very difficult to make, so clinicians may refer
to these classification systems for guidance.
One of the most commonly used systems for diagnosing
lupus was developed in 1971 by the American College of
Rheumatology (ACR) and is known as the ACR SLE clas-
sification criteria. This system was revised in 1982 and
again 1997 (Table 2).10,11 The presence of four of the 11
criteria (concurrently or consecutively on two separate
occasions) yields a sensitivity of 86% and a specificity of
93% for diagnosing lupus.10,11
In 2012, the Systemic Lupus International Collaborating
Clinics (SLICC) group, an international group dedicated
to lupus research, modified and validated the ACR criteria
and came up with new criteria called the SLICC criteria.
The reason for the modification was due to many drawbacks
that became apparent with the ACR criteria.12 One of these
concerns included duplication of highly associated terms
such as malar rash and photosensitivity. The criteria also
failed to include other cutaneous and neurologic symptoms
of lupus, or exclude low complement levels in its immu-
nologic criteria.12 In addition to these limitations, the ACR
criteria were never validated. Overall the revision’s goal
TABLE 2. ACR criteria for systemic lupus erythematosus
Patients must meet four criteria for a diagnosis of lupus.
• Malar rash
• Discoid rash
• Photosensitivity—patient history or provider observation
• Oral or nasopharyngeal ulcers
• Nonerosive arthritis—tenderness, swelling, or effusion in
two or more peripheral joints
• Pleurisy (a convincing history of pleuritic pain, pleural
rub, or effusion) or pericarditis (ECG evidence, rub, or
effusion)
• Renal abnormalities—persistent proteinuria (>0.5 g/day
or >3+ by dipstick) or cellular casts on microscopy (red,
granular, tubular, or mixed)
• Neurologic abnormalities—seizures of psychosis in the
absence of drugs or metabolic derangements
• Hematologic abnormalities—at least one of the following:
hemolytic anemia with reticulocytosis, leukopenia (<4,000
cells/mm3) on two or more occasions, lymphopenia
(<1,500 cells/mm3 on two or more occasions), or throm-
bocytopenia (<100,000 cells/mm3) not caused by drugs
• Immunologic abnormalities—at least one of the following:
anti-DNA antibody, anti-Smith antibody, or positive
antiphospholipid antibodies identified by a positive lupus
anticoagulant or an abnormal serum level of IgM or IgG
anticardiolipin antibodies
• Positive antinuclear antibodies.
Adapted with permission from Hochberg MC. Updating the American
College of Rheumatology revised criteria for the classification of
systemic lupus erythematosus. Arthritis Rheum. 1997;40(9):1725.
24 www.JAAPA.com
Copyright © 2015 American Academy of Physician Assistants
was to make the criteria more consistent with lupus’ evolv-
ing pathogenesis.
SLICC criteria require the patient to meet at least four
criteria, including one clinical criterion and one immuno-
logic criterion, or the patient must have confirmed lupus
nephritis via a biopsy with positive antinuclear (ANA)
antibodies or anti-double-stranded-DNA (anti-dsDNA)
antibodies (Table 3).12 A study that evaluated the SLICC
and ACR lupus criteria revealed that, “In the derivation
sample researchers concluded the SLICC misclassified fewer
cases and had higher sensitivity (94%) but lower specific-
ity (92%) compared with the ACR criteria 86% and 93%.
In the validation sample the SLICC had a sensitivity of
97% and specificity of 84% compared with ACR, which
was 83% and 96%.”12 To date, no one set of criteria has
taken precedence.12
SERUM MARKERS
Some of the more notable serologic markers supporting
the diagnosis of lupus are ANA and anti-dsDNA antibod-
ies. ANA tests have a low specificity and can be positive
for many rheumatologic conditions.6,13 Only 11% to 13%
of patients with positive ANA tests have a confirmed
diagnosis of lupus.14 ANA also can be positive in 3% to
15% of healthy patients of all ages, and in 10% to 37%
of healthy patients over age 65 years.14
The two most popular ANA tests are the indirect immu-
nofluorescence assay (IFA) and the enzyme-linked immu-
nosorbent assay (ELISA). The IFA is the gold standard for
ANA detection because of its higher specificity, although
the ELISA is more sensitive.15 Some experts recommend
screening for ANA with ELISA if the clinician has a strong
suspicion of a connective tissue disorder based on the
patient’s signs and symptoms, then confirming the results
with an IFA.15
The presence of ANA in healthy people has raised many
questions. The assay system used to detect ANA and
intrinsic immunologic disturbances may cause positive
results.13,16 ANA appears to be more prevalent among
women, older adults, and blacks, and less common in
patients who are obese.17
An extractable nuclear antigen (ENA) panel can be used
when the ANA is positive and the clinician strongly suspects
lupus. This test includes anti-ribonucleoprotein, anti-Smith,
anti-SS-A (Ro), and anti-SS-B (La) autoantibodies.18 When
positive, these markers may be associated with certain
lupus manifestations. For example, anti-SS-A (Ro) has
been linked to serositis, cutaneous lupus, and hematologic
symptoms.19 Anti-RNP has shown correlation with arthri-
tis and Raynaud syndrome.19 Ro and La antibodies can
cross the placenta and cause neonatal lupus.20 Anti-Sm
antibodies usually reflect the severity and activity of renal
involvement.21
Patients with false-positive diagnostic test results may
be at risk for lupus or other autoimmune diseases, and
Volume 28 • Number 9 • September 2015

should be followed closely because antibody positivity
TABLE 3.
can precede symptoms.22 Careful monitoring can help
patients obtain early aggressive treatment and reduce
the likelihood for a severe course if they develop the
disease.
ORGAN DAMAGE AND COMORBIDITIES
Lupus-related organ damage is defined as any irreparable
tissue damage occurring since the diagnosis of lupus and
lasting at least 6 months.23 Damage can result from the
disease or its treatments, and tends to accrue over time.
One area that is still under deliberation is whether disease-
induced damage or treatment-induced damage should be
categorized as different measures or as one.2,3 Lopez and
colleagues found that age, renal activity, immunosuppres-
sant use, and preexisting burden of organ damage were
major predictive factors of irreparable organ damage and
mortality.24 The SLICC Inception Cohort determined that
increasing age, male sex, black Americans, and Hispanic
residents of Mexico all had a higher risk of damage accrual.25
Lupus also is associated with many comorbid condi-
tions, including cardiovascular disease (CVD), nephritis,
and osteoporosis; T2T strategies hope to target these
conditions.
CVD The chronic inflammation caused by lupus appears
to cause coronary microvascular dysfunction.26 Women
with lupus have twice the risk of CVD as women without
lupus; pericarditis is one of the most common cardiac
complications in patients with lupus.27,28 Myocarditis,
endocarditis, and coronary artery disease also are common
in patients with lupus.27
Lupus nephritis Characterized by proteinuria, hematu-
ria, rising anti-dsDNA levels, and low complement levels,
lupus nephritis affects 40% of patients and is more common
in women, blacks, and Hispanics.29,30
Osteoporosis This common comorbidity can be attributed
to the recommendation for patients with lupus to avoid
sun exposure, the association between the disease and renal
impairment, the overall inflammatory component of the
disease, and patients’ chronic use of corticosteroids.31
Corticosteroids pose a clinical challenge because they suc-
cessfully treat lupus, but cause adverse reactions and
contribute to organ damage.3 Because of the association
between corticosteroids and organ damage, using the low-
est corticosteroid dose possible is an important T2T goal.2,3
Patients with lupus who develop these or other comor-
bidities may have a more complicated disease course and
decreased survival, making early diagnosis, treatment, and
follow-up critical to preventing organ damage.
CURRENT TREATMENTS
The goal of treatment for rheumatic conditions, including
lupus, is to suppress the immune system, reduce inflam-
mation, decrease disease activity, prevent flares, and achieve
remission. Lupus has a varied course depending on the
JAAPA Journal of the American Academy of Physician Assistants
Copyright © 2015 American Academy of Physician Assistants
Systemic lupus erythematosus: An update on treat-to-target
SLICC clinical and immunologic criteria
Criteria are cumulative and need not be present concur-
rently. A patient has systemic lupus erythematosus if she or
he meets at least four criteria, including one clinical
criterion and one immunologic criterion, or has confirmed
lupus nephritis via a biopsy with positive ANA or anti-
dsDNA antibodies.
Clinical criteria
• Acute cutaneous lupus—lupus malar rash (do not count if
malar discoid), bullous lupus, toxic epidermal necrolysis
variant of lupus, maculopapular lupus rash, photosensitive
lupus rash, or subacute cutaneous lupus (nonindurated
psoriaform and/or annular polycystic lesions that resolve
without scarring, although occasionally with postinflamma-
tory dyspigmentation or telangiectasias)
• Chronic cutaneous lupus—classical discoid rash
(localized—above the neck; generalized—above and
below the neck), hypertrophic (verrucous) lupus, lupus
panniculitis (profundus), mucosal lupus, lupus erythema-
tosus turnidus, chilblains lupus, discoid lupus/lichen
planus overlap
• Oral ulcers—palate (buccal, tongue) or nasal ulcers in
the absence of other causes
• Nonscarring alopecia
• Synovitis—two or more joints, characterized by swelling
or effusion, or tenderness in two or more joints and 30
minutes or more of morning stiffness
• Renal abnormalities—urine protein/creatinine ratio (or
24-hour urine protein) representing 500 mg protein in 24
hours, or red blood cells casts
• Neurologic abnormalities—seizures, psychosis, mononeu-
ritis multiplex, myelitis, peripheral or cranial neuropathy,
acute confusional state (in the absence of other causes)
• Hemolytic anemia
• Leukopenia (<4,000 cells/mm3 at least once) or lympho-
penia (<1,000 cells/mm3 at least once)
• Thrombocytopenia—platelets <100,000 cells/mm3 at
least once
Immunologic criteria
• ANA above reference range
• Anti-dsDNA two or more times normal level if measured
via ELISA
• Anti-Smith
• Antiphospholipid—lupus anticoagulant, false-positive
RPR, medium- or high-titer anticardiolipin (IgA, IgG, or
IgM), anti-beta2 glycoprotein I (IgA, IgG, or IgM)
• Low complement (low C3, C4, or CH50)
• Positive direct Coombs test in the absence of hemolytic
anemia
Adapted with permission from Petri M, Orbai AM, Alarcón GS,
et al. Derivation and validation of the systemic lupus international
collaborating clinics classification criteria for systemic lupus
erythematosus. Arthritis Rheum. 2012;64(8):2677-2686.
www.JAAPA.com 25
CME
patient, so treatment goals vary. Treatment is continuing
to evolve and improve; however, lupus has no cure.
Belimumab, the newest drug for lupus, was approved in
2011.32 Previously, the only approved drugs for lupus were
hydroxychloroquine, corticosteroids, and aspirin.32 Beli-
mumab is a biologic that inhibits the B-lymphocyte stimu-
lator, a pathological factor in patients with lupus.33-35
Patients with low complement levels, anti-dsDNA positiv-
ity, and more severe disease appear more responsive to
belimumab in combination with standard therapy than to
standard therapy alone.33
Rituximab, another biologic that targets B cells, was
unsuccessful at achieving and maintaining a major clinical
response (maintaining stable mild or inactive disease with-
out a moderate or severe flare by week 52).36,37 However,
patients receiving rituximab did have a significant improve-
ment in their anti-dsDNA and complement levels, which
correlated with reductions in proteinuria.38 Patients taking
biologics as the primary treatment must receive appropri-
ate vaccinations (such as an annual influenza vaccine and
pneumococcal pneumonia vaccine) at baseline due to the
risk of immunosuppression. However, patients should
avoid live vaccines while taking immunosuppressants, and
should be monitored closely for signs of infection.
The antimalarial drug hydroxychloroquine was found
to exert a protective effect on survival in addition to
controlling flares and disease activity in patients with
lupus.39 Antimalarial drugs usually have anti-inflamma-
tory and antithrombotic properties, and are added to the
regimen to reduce the dosages of other required medica-
tions.39,40 One of the advantages of hydroxychloroquine
is its high tolerability compared with corticosteroids;
hydroxychloroquine usually is given for the length of the
disease, and can be taken by pregnant women without
harming the fetus.39-41 Dosages may need to be adjusted
for patients with kidney damage or low body weight.41
Although this drug causes few adverse reactions, rarely,
patients may develop retinal toxicity, so the ACR recom-
mends that all patients starting hydroxychloroquine have
a baseline ophthalmologic examination within the first
year of treatment.41,42
Corticosteroids control the inflammation associated with
lupus and suppress the immune system. They can be
administered orally, intramuscularly, topically, or IV (for
high doses over a short period of time).43 Higher doses
usually are reserved for patients with more severe compli-
cations, such as nephritis or myocarditis. Because of con-
cern over the long-term adverse reactions to corticosteroids,
a goal of T2T is to have patients on the lowest effective
dose of corticosteroids.37,44 Patients taking long-term cor-
ticosteroids should be monitored for osteoporosis and
cataracts.
Medications that are used off-label for lupus (due to the
complexity of treating the disease) include rituximab,
azathioprine, mycophenolate, and methotrexate.45
26 www.JAAPA.com
Copyright © 2015 American Academy of Physician Assistants
T2T GOALS FOR LUPUS
Using T2T for rheumatic conditions is more complicated
than using it for diabetes or hypertension because the goal
is a reduction in disease activity or remission, rather than
a numeric target such as A1C or BP.5 The T2T recom-
mendations for lupus were developed by a working group
of specialists proficient in research and treatment of lupus
and an international expert panel.3 The recommendations
are steppingstones that providers can use, along with
clinical judgment, to apply T2T to lupus.3 Primary T2T
goals should be to achieve remission, prevent damage
accrual, and improve health-related quality of life to reduce
patient morbidity and mortality.2,3 When remission is not
feasible, the target should be the lowest possible disease
activity.3 These targets have been the primary endpoints
of many studies of T2T for rheumatoid arthritis, and can
be measured by the various disease activity/damage indices
discussed below.
Remission The main obstacle to using remission as a
target is that the task force and other researchers have been
unable to agree on a definition of remission from lupus.3
One study defined complete remission as clinical and
laboratory dormancy in a patient no longer taking corti-
costeroid, antimalarial, or immunosuppressive treatment.46
However, patients could be taking nonsteroidal anti-
inflammatory therapy. Prolonged remission was defined
as remission for 5 years. However, this study determined
that both prolonged and complete remissions were rare.
Prolonged remission only occurred in 1.7% of patients
and 6.5% of patients achieved complete remission for at
least 1 year.46
Preventing organ damage Because of its large effect on
prognosis and the connection between organ damage and
subsequent impairment, preventing damage accrual is a
key treatment target.3 Predicting and preventing lupus-
related organ damage has always been a major obstacle
for clinicians and researchers.24 Research demonstrates
that damage accrual was associated with higher disease
activity and corticosteroid use.24,25 Ruiz-Arruza found
that 21% of patients on no prednisone accrued organ
damage, compared with 30% on low doses (7.5 mg/day
or less) and 53% on medium (7.5 to 30 mg/day) to high
doses (more than 30 mg/day). The primary damage
observed in these patients was cataracts, osteoporotic
fractures, avascular necrosis, and diabetes.43 The task
force was unable to come up with a safe dose of cortico-
steroids so the recommendation is to have patients on
the lowest effective dose.3
Improving health-related quality of life Fatigue, depres-
sion, and pain can have devastating effects, so health-related
quality of life is another primary T2T target. Although
treatment decisions are based on remission, low disease
activity, and damage prevention, factors that improve
quality of life also must be considered as patients achieve
long-term survival.3
Volume 28 • Number 9 • September 2015

Reducing disease activity Because remission is not always
possible, low disease activity is a more realistic target.
Disease activity, which can be reversed by treatment, can
be relapsing-remitting, chronically active, or long quiescent.2
(Damage, in contrast, is irreversible.2) Lower disease activ-
ity has been associated with a reduction in damage accrual
and improved prognosis.47 Because disease activity is a
major therapeutic target, researchers are trying to develop
a validated index to assess disease activity in clinical trials.
Clinicians now use clinical expertise to evaluate disease
activity in routine clinical practice.2
ASSESSING T2T GOALS
Assessing disease activity, organ damage, and quality of
life are important to monitor response to therapy, predict
future organ damage, and determine if T2T goals are being
met. No one instrument has been confirmed as the standard
measurement system. Some available assessment tools are
described below; health-related quality of life assessments
also can be used.48-50
Physician Global Assessment (PGA) Considered by many
as the gold standard measurement tool for disease activity,
the PGA can be used to determine if T2T goals are being
met.48,49 This tool uses a visual analog scale to assess activ-
ity globally and by organ system.49 The tool is quick and
easy to use, but many providers have varying opinions on
its level of importance.49
SRI One of the newer disease activity indices, SRI com-
bines three disease assessments: Safety of Estrogen in Lupus:
National Assessment-SLE Disease Activity Index, British
Isles Lupus Assessment Group Scale, and PGA, and assesses
disease improvement and treatment responsiveness.51
Because of the time needed for this tool, it is mostly used
in clinical trials.51
Health-related quality of life is assessed via questionnaires
such as the Lupus Quality of Life (LupusQoL), Systemic
Lupus Erythematosus-Specific Quality-of-Life, and SLE
Quality of Life.52 The LupusQoL is the most validated of
these tools.53
CONCLUSION
After a sudden decrease in mortality among patients with
lupus, mortality has plateaued in the last 30 years.47 This
triggered the need for other approaches such as T2T, which
are aimed at achieving complete remission possible and
ultimately stopping the acceleration of end-organ damage.
Because lupus has such an unpredictable and inconsistent
progression, a standardized way is needed to assess disease
activity and flares in order to develop T2T goals, formulate
appropriate treatment plans, and determine if the targets
are being reached. Treatment guidelines are still evolving
to incorporate a T2T model; however, the research on T2T
is still in the nascent phases. T2T has shown great success
in the treatment and prognosis of rheumatoid arthritis,
diabetes, spondyloarthritis, and other chronic conditions,
JAAPA Journal of the American Academy of Physician Assistants
Copyright © 2015 American Academy of Physician Assistants
Systemic lupus erythematosus: An update on treat-to-target
so the future of using this strategy to effectively manage
lupus has great potential.2
Until adequate evidence supports the T2T approach in
patients with lupus, providers must work collaboratively
following the current standard of care to help control this
disease. Like many other diseases, early intervention and
diagnosis is key to reducing morbidity, mortality, and
healthcare-related costs.54 JAAPA
Earn Category I CME Credit by reading both CME articles in this issue,
reviewing the post-test, then taking the online test at http://cme.aapa.org.
Successful completion is defined as a cumulative score of at least 70%
correct. This material has been reviewed and is approved for 1 hour of
clinical Category I (Preapproved) CME credit by the AAPA. The term of
approval is for 1 year from the publication date of September 2015.
REFERENCES
1. Danchenko N, Satia JA, Anthony MS. Epidemiology of systemic
lupus erythematosus: a comparison of worldwide disease
burden. Lupus. 2006;15(5):308-318.
2. Mosca M, Boumpas DT, Bruce IN, et al. Treat-to-target in
systemic lupus erythematosus: where are we today? Clin Exp
Rheumatol. 2012;30(4 suppl 73):S112-S115.
3. van Vollenhoven RF, Mosca M, Bertsias G, et al. Treat-to-target
in systemic lupus erythematosus: recommendations from an
international task force. Ann Rheum Dis. 2014;73(6):958-967.
4. Pincus T, Castrejón I. Evidence that the strategy is more
important than the agent to treat rheumatoid arthritis. Data
from clinical trials of combinations of non-biologic DMARDS,
with protocol-driven intensification of therapy for tight control
or treat-to-target. Bull Hosp Jt Dis. 2013;71(suppl 1):S33-S40.
5. Doria A, Gatto M, Zen M, et al. Optimizing outcome in SLE:
treating-to-target and definition of treatment goals. Autoimmun
Rev. 2014;13(7):770-777.
6. Bertsias G, Cervera R, Boumpas D. Systemic lupus erythemato-
sus: pathogenesis and clinical. In: Bijlsma JWJ, ed. EULAR
Textbook of Rheumatic Diseases. 1st ed. London: BMJ Group;
2012:476-505.
7. Antonov D, Kazandjieva J, Etugov D, et al. Drug-induced lupus
erythematosus. Clin Dermatol. 2004;22(2):157-166.
8. American College of Rheumatology. Systemic lupus erythemato-
sus (lupus). www.rheumatology.org/practice/clinical/patients/
diseases_and_conditions/lupus.asp. Accessed June 10, 2015.
9. Mak A, Cheung MW, Chiew HJ, et al. Global trend of survival
and damage of systemic lupus erythematosus: meta-analysis and
meta-regression of observational studies from the 1950s to
2000s. Semin Arthritis Rheum. 2012;41(6):830-839.
10. American College of Rheumatology. 1997 Update of the 1982
American College of Rheumatology revised criteria for classifica-
tion of systemic lupus erythematosus. https://www.rheumatology.
org/Practice/Clinical/Classification/SLE/1997_Update_of_Revised_
Systemic_Lupus_Erythematosus. Accessed June 10, 2015.
11. Hochberg MC. Updating the American College of Rheumatology
revised criteria for the classification of systemic lupus erythemato-
sus. Arthritis Rheum. 1997;40(9):1725.
12. Petri M, Orbai AM, Alarcón GS, et al. Derivation and Valida-
tion of the systemic lupus international collaborating clinics
classification criteria for systemic lupus erythematosus. Arthritis
Rheum. 2012;64(8):2677-2686.
13. Wichainun R, Kasitanon N, Wangkaew S, et al. Sensitivity and
specificity of ANA and anti-dsDNA in the diagnosis of systemic
lupus erythematosus: a comparison using control sera obtained
from healthy individuals and patients with multiple medical
problems. Asian Pac J Allergy Immunol. 2013;31(4):292-298.
www.JAAPA.com 27
CME
14. American College of Rheumatology. Antinuclear antibodies
(ANA). https://www.rheumatology.org/Practice/Clinical/Patients/
Diseases_And_Conditions/Antinuclear_Antibodies_(ANA)/.
Accessed June 10, 2015.
15. Copple SS, Sawitzke AD, Wilson AM, et al. Enzyme-linked
immunosorbent assay screening then indirect immunofluores-
cence confirmation of antinuclear antibodies: a statistical
analysis. Am J Clin Pathol. 2011;135(5):678-684.
16. Pisetsky DS. Antinuclear antibodies in healthy people: the tip of
autoimmunity’s iceberg? Arthritis Res Ther. 2011;13(2):109.
17. Satoh M, Chan EK, Ho LA, et al. Prevalence and sociodemo-
graphic correlates of antinuclear antibodies in the United States.
Arthritis Rheum. 2012;64(7):2319-2327.
18. Lab Tests Online. ENA Panel. American Association for Clinical
Chemistry. http://labtestsonline.org/understanding/analytes/
ena-panel/tab/test. Accessed June 25, 2015.
19. Cozzani E, Drosera M, Gasparini G, Parodi A. Serology of lupus
erythematosus: correlation between immunopathological features
and clinical aspects. Autoimmune Dis. 2014;2014:321359.
20. Lupus Foundation of America website. What are the laboratory
tests for Lupus? www.lupus.org/answers/entry/lupus-tests.
Accessed June 25, 2015.
21. Migliorini P, Baldini C, Rocchi V, Bombardieri S. Anti-Sm and
anti-RNP antibodies. Autoimmunity. 2005;38(1):47-54.
22. Isenberg DA, Manson JJ, Ehrenstein MR, Rahman A. Fifty years
of anti-ds DNA antibodies: are we approaching journey’s end?
Rheumatology (Oxford). 2007;46(7):1052-1056.
23. Gladman DD, Urowitz MB, Goldsmith CH, et al. The reliability of
the Systemic Lupus International Collaborating Clinics/American
College of Rheumatology damage index in patients with systemic
lupus erythematosus. Arthritis Rheum. 1997;40(5):809-813.
24. Lopez R, Davidson JE, Beeby MD, et al. Lupus disease activity
and the risk of subsequent organ damage and mortality in a
large lupus cohort. Rheumatology (Oxford). 2012;51(3):
491-498.
25. Bruce IN, O’Keeffe AG, Farewell V, et al. Factors associated with
damage accrual in patients with systemic lupus erythematosus:
results from the Systemic Lupus International Collaborating Clinics
(SLICC) Inception Cohort. Ann Rheum Dis. [e-pub May 16, 2014].
26. Knight JS, Kaplan MJ. Cardiovascular disease in lupus: insights
and updates. Curr Opin Rheumatol. 2013;25(5):597-605.
27. Lupus Foundation of America. How does lupus affect the heart
and circulation? www.lupus.org/answers/entry/lupus-and-the-
heart. Accessed June 25, 2015.
28. Hak AE, Karlson EW, Feskanich D, et al. Systemic lupus
erythematosus and the risk of cardiovascular disease: results from
the nurses’ health study. Arthritis Rheum. 2009;61(10):1396-1402.
29. Lupus Foundation of America. How does lupus affect the renal
(kidney) system? www.lupus.org/answers/entry/lupus-and-
kidneys. Accessed June 25, 2015.
30. Saxena R, Mahajan T, Mohan C. Lupus nephritis: current
update. Arthritis Res Ther. 2011;13(5):240.
31. García-Carrasco M, Mendoza-Pinto C, Escárcega RO, et al.
Osteoporosis in patients with systemic lupus erythematosus. Isr
Med Assoc J. 2009;11(8):486-490.
32. US Food and Drug Administration. FDA approves Benlysta
to treat lupus. www.fda.gov/newsevents/newsroom/
pressannouncements/ucm246489.htm. Accessed June 25, 2015.
33. van Vollenhoven RF, Petri MA, Cervera R, et al. Belimumab in the
treatment of systemic lupus erythematosus: high disease activity
predictors of response. Ann Rheum Dis. 2012;71(8):1343-1349.
34. Sanz I, Lee FE. B cells as therapeutic targets in SLE. Nat Rev
Rheumatol. 2010;6(6):326-337.
35. Wallace DJ, Stohl W, Furie RA, et al. A phase II, randomized,
double-blind, placebo-controlled, dose-ranging study of
belimumab in patients with active systemic lupus erythematosus.
Arthritis Rheum. 2009;61(9):1168-1178.
36. Mosca M, van Vollenhoven R. New drugs in systemic lupus
erythematosus: when to start and when to stop. Clin Exp
Rheumatol. 2013;31(4 suppl 78):S82-S85.
28 www.JAAPA.com
Copyright © 2015 American Academy of Physician Assistants
37. Merrill JT, Neuwelt CM, Wallace DJ, et al. Efficacy and safety of
rituximab in moderately-to-severely active systemic lupus
erythematosus: the randomized, double-blind, phase II/III
systemic lupus erythematosus evaluation of rituximab trial.
Arthritis Rheum. 2010;62(1):222-233.
38. Rovin BH, Furie R, Latinis K, et al. Efficacy and safety of
rituximab in patients with active proliferative lupus nephritis:
the lupus nephritis assessment with rituximab study. Arthritis
Rheum. 2012;64(4):1215-1226.
39. Alarcón GS, McGwin G, Bertoli AM, et al. Effect of hydroxy-
chloroquine on the survival of patients with systemic lupus
erythematosus: data from LUMINA, a multiethnic US cohort
(LUMINA L). Ann Rheum Dis. 2007;66(9):1168-1172.
40. Lupus Foundation of America. What medications are used to
treat lupus? www.lupus.org/answers/entry/medications-to-treat-
lupus. Accessed June 25, 2015.
41. Lupus Foundation of America. Spotlight on hydroxychloro-
quine. www.lupus.org/magazine/entry/drug-spotlight-on-
hydroxychloroquine. Accessed June 25, 2015.
42. American Optometric Association. Retinal toxicity from
hydroxychloroquine. www.aoa.org/optometrists/education-and-
training/clinical-care/retinal-toxicity-from-hydroxychloroquine?
sso=y. [account required]. Accessed January 24, 2015.
43. Ruiz-Arruza I, Ugarte A, Cabezas-Rodriguez I, et al. Glucocorti-
coids and irreversible damage in patients with systemic lupus
erythematosus. Rheumatology (Oxford). 2014;53(8):1470-1476.
44. van der Goes MC, Jacobs JW, Boers M, et al. Monitoring
adverse events of low-dose glucocorticoid therapy: EULAR
recommendations for clinical trials and daily practice. Ann
Rheum Dis. 2010;69(11):1913-1919.
45. Lupus Research Institute. Lupus treatments. www.lupusresearch
institute.org/lupus-facts/lupus-treatments. Accessed June 30, 2015.
46. Urowitz MB, Feletar M, Bruce IN, et al. Prolonged remission in
systemic lupus erythematosus. J Rheumatol. 2005;32(8):1467-1472.
47. Wangnoo SK, Sethi B, Sahay RK, et al. Treat-to-target trials in
diabetes. Indian J Endocrinol Metab. 2014;18(2):166-174.
48. Mosca M, Bombardieri S. Assessing remission in systemic lupus
erythematosus. Clin Exp Rheumatol. 2006;24(6 suppl 43):
S100-S104.
49. Petri M. Measuring disease activity and severity in clinical trials
and then the clinic: same or different? Treatment of SLE:
bridging the gap from the clinical trials to practice. Annual
Congress of the American College of Rheumatology,
Washington, DC, November 11, 2012.
50. Kiani AN, Strand V, Fang H, et al. Predictors of self-reported
health-related quality of life in systemic lupus erythematosus.
Rheumatology (Oxford). 2013;52(9):1651-1657.
51. Luijten KM, Tekstra J, Bijlsma JW, Bijl M. The systemic lupus
erythematosus responder index (SRI): a new SLE disease activity
assessment. Autoimmun Rev. 2012;11(5):326-329.
52. Romero-Diaz J, Isenberg D, Ramsey-Goldman R. Measures of
adult systemic lupus erythematosus: updated version of British
Isles Lupus Assessment Group (BILAG 2004), European
Consensus Lupus Activity Measurements (ECLAM), Systemic
Lupus Activity Measure, Revised (SLAM-R), Systemic Lupus
Activity Questionnaire for Population Studies (SLAQ),
Systemic Lupus Erythematosus Disease Activity Index 2000
(SLEDAI-2K), and Systemic Lupus International Collaborating
Clinics/American College of Rheumatology Damage Index (SDI).
Arthritis Care Res (Hoboken). 2011;63(suppl 11):S37-S46.
53. Yazdany J. Health-related quality of life measurement in
adult systemic lupus erythematosus: Lupus Quality of Life
(LupusQoL), Systemic Lupus Erythematosus-Specific Quality
of Life Questionnaire (SLEQOL), and Systemic Lupus Erythema-
tosus Quality of Life Questionnaire (L-QoL). Arthritis Care Res
(Hoboken). 2011;63(suppl 11):S413-S419.
54. Turchetti G, Yazdany J, Palla I, et al. Systemic lupus erythemato-
sus and the economic perspective: a systematic literature review
and points to consider. Clin Exp Rheumatol. 2012;30(4 suppl
73):S116-S122.
Volume 28 • Number 9 • September 2015