ARTHRITIS & RHEUMATISM
Vol. 39, No. 5 , May 1996, pp 713-722
8 1996, American College of Rheumatology
Arthritis & Rheumatism
Official Journal of the American College of Rheumatology
SPECIAL ARTICLE
GUIDELINES FOR THE MANAGEMENT O F RHEUMATOID ARTHRITIS
AMERICAN COLLEGE OF KHEUMATOLOGY AD HOC COMMITTEE ON CLINICAL GUIDELINES
Rheumatoid arthritis (RA) is an autoimmune
disorder of unknown etiology characterized by sym-
metric, erosive synovitis and sometimes multisystem
involvement (1). Most patients exhibit a chronic fluc-
tuating course of disease that, if left untreated, results
in progressive joint destruction, deformity, disability,
and premature death (2). RA results in more than 9
million physician visits and more than 250,000 hospi-
talizations per year (3). It frequently affects patients in
their most productive years, and thus, disability re-
sults in major economic loss. It has been estimated
that working individuals with arthritis have a yearly
earnings deficit of $17.6 billion (1986 dollars) compared
with earnings of individuals without arthritis, and $6.5
billion of this shortfall is attributable to RA (3).
RA affects 1% of the adult population (2). This
low prevalence means that the average physician often
develops little experience with its diagnosis or man-
agement. The following guidelines for the management
Members of the Ad Hoc Committee on Clinical Guidelines
are as follows. C. Kent Kwoh, MD (co-chair): Case Western
Reserve University, Cleveland, Ohio; Robert W. Simms, MD (co-
chair): Boston University School of Medicine, Boston, Massachu-
setts; Larry G. Anderson, MD: Rheumatology Associates, Portland,
Maine; Diane M. Erlandson, RN, MS, MPH: Harvard School of
Public Health, Boston, Massachusetts; Jerry M. Greene, MD:
Veterans Affairs Medical Center, West Roxbury, Massachusetts;
Carolee Moncur, PhD, PT: tiniversity of Utah, Salt Lake City;
James R. O’Dell, MD: University of Nebraska Medical Center,
Omaha; Alison J. Partridge, LICSW: Robert B. Brigham Multipur-
pose Arthritis and Musculoskeletal Diseases Center, Boston, Mas-
sachusetts; W. Neal Roberts, MD: Medical College of Virginia,
Richmond; Mark L. Robbins, MD, MPH: Harvard Pilgrim Health
Care, Boston, Massachusetts; Robert A. Yood, MD: Fallon Clinic,
Worcester, Massachusetts; Matthew H. Liang, MD, MPH: Brigham
and Women’s Hospital, Boston, Massachusetts.
Address reprint requests to American College of Rheuma-
tology, 60 Executive Park South, Suite 150, Atlanta, GA 30329.
Submitted for publication August 9, 1995; accepted in
revised form March 4, 19%.
713
of RA assume a correct diagnosis, which may be
difficult in the earlier stages (4). If there is any uncer-
tainty about the diagnosis, consultation with a rheu-
matologist should be considered.
A detailed algorithm for management would be
an unjustified simplification of the many decisions that
must be made over the course of a patient’s illness.
Instead, these guidelines outline the treatment op-
tions, the critical decisions, and the essential skills and
knowledge necessary for optimal care. This set of
guidelines was developed by a group of rheumatolo-
gists, primary care physicians who practice rheuma-
tology, and other arthritis health professionals based
on consensus, and on literature review where pub-
lished data were available. Separate guidelines address
the monitoring of medications used in RA (5). Al-
though much is known, the lack of data necessitates
that these guidelines must also be based in part on
community standards of care.
Goals of treating rheumatoid arthritis
There is no known cure for RA or means of
preventing it. Optimal management requires early di-
agnosis and timely introduction of agents that reduce
the probability of irreversible joint damage. Figure 1
outlines an approach to the evaluation and treatment
of the patient after the diagnosis has been established.
Periodic assessment of disease activity, drug toxicity,
and the effectiveness of the treatment program is
essential, with revisions of the treatment program as
nccessary.
Studies show that patients with active, poly-
articular, rheumatoid factor (RFbpositive RA have a
>70% probability of developing joint damage or ero-
sions within 2 years of the onset of disease (610).
714 ACR CLINICAL GUIDELINES COMMITTEE

.. -.~
[ Establish Diagnosis
~

- of Rheumatoid A r t h r i t i d

-Disease activity and extent of synovitis

-Structural damage

JI

J
Initiate Treatment
*Patient education
.Physical and occupatioiial therapy, etc.
*h'SAIDs
.Possible local or oral steroids ( 5 10 mg. Prednisone)
~.

JI
Spontnneoics fhiissiori
(iincoinnion)
+ Periodically
Persistent Artiue Disease

JI

Control

Persistent Active 1)beaAe ( 0\5ease

4 &\@
;\0* O'

- Consult Rheuniatologist
.Change NShIDs
* Chaiige/add DMARDs
Remission 07 Sds/nrtor! + Periodically
-- ~

.I.ocal or oral steroids

Symptoms r
Pewistent Acfioe Discuse
o\ 6"
JI &J~
,

"""

Mechanical
. $Joint y m
Consul&Hheuma~ologist
~ o < ~ ~ ~ ~ h ~
- Most effective NSAlD
- Most effective DMARD (single or conibinatioii) Hemissiu7io~SnliAfucrory Coirfrol
.Possible local or oral steroids
*Rehabilitative measures

Figure 1. Management of rheumatoid arthritis. See the text for a discussion of monitoring of disease activity
and adequacy of the treatment program, and for descriptions of persistent active disease and disease
remission. NSAID = nonsteroidal antiinflammatorydrug; DMARD = disease-modifying antirheumaticdrug.

Other studies suggest that early aggressive treatment
may alter the disease course (11,12), and most rheu-
matologists who care for patients with RA favor
aggressive treatment early in the course of the disease.
While the ultimate goal of treating RA is to
induce a complete remission, this occurs only in rare
cases. Complete remission is defined as the absence of
1) symptoms of active inflammatory joint pain (in
contrast to mechanical joint pain), 2) morning stiff-
ness, 3) fatigue, 4) synovitis on joint examination, 5 )
progression of radiographic damage on sequential ra-
diographs, and 6) elevated erythrocyte sedimentation
GUIDELINES FOR RA MANAGEMENT
Table 1. Baseline evaluation of patients with rheumatoid arthritis
Subjective
Degree of joint pain
Duration of AM stiffness
Presence or absence of fatigue
Limitation of function
Physical examination
Documentation of actively inflamed joints
Documentation of mechanical joint problems: loss of motion,
crepitus, instability, malalignment and/or deformity
Documentation of extraarticular manifestations
Laboratory
Erythrocyte sedimentation rate/C-reactive protein
Rheumatoid factor*
Complete blood cell count?
Electrolytes?
Creatininet
Hepatic panel:
Urinalysist
Synovial fluid analysis$
Stool guaiact
Radiography
Radiography of selected involved joints5
* Performed only at baseline to establish the diagnosis; may be
repeated 6-12 months after disease onset if negative initially.
t Performed at baseline to assess organ dysfunction due to comor-
bid diseases, before starting medications.
$ Performed at baselinc if necessary, to rule out other diseases; may
be repeated during disease flares to rule out septic arthritis.
0 May have limited diagnostic value early in the disease, but helps to
establish a baseline for periodically monitoring disease progression
and response to treatment.
rate (ESR) or C-reactive protein (CRP) level (13). If
complete remission is not achieved, the management
goals are to control disease activity, alleviate pain,
maintain function for essential activities of daily living
and work, maximize quality of life, and slow the rate
of joint damage.
Initial evaluation and treatment of rheumatoid
arthritis
The initial evaluation of the patient with RA
should document symptoms of active disease (joint
pain, morning stiffness, fatigue), functional status,
objective evidence of disease activity (synovitis, ESR
or CRP level), mechanical joint problems, the pres-
ence of extraarticular disease and comorbid condi-
tions, and the presence of radiographic damage in
selected involved joints (Table 1). Later comparison
with this baseline information facilitates assessment of
disease progression and response to treatment.
Careful history-taking, a complete review of
systems, and a thorough physical examination (both
general and musculoskeletal) are necessary. The se-
verity and duration of morning stiffness and constitu-
715
tional symptoms such as fatigue should be recorded.
Patient’s and physician’s global assessment, tender
and swollenjoint counts, a quantitative assessment of
pain by a visual analog scale or other mechanism, and
functional evaluation are useful parameters to follow
during the course of the disease (14,15).
Baseline laboratory evaluations should include
complete blood cell count (CBC), platelet count,
chemistry profile, RF measurement, and measurement
of ESR or CRP. Evaluation of renal and hepatic
function is necessary since many antirheumatic agents
have renal or hepatic toxicity and may be contraindi-
cated if these organs are impaired. Initial radiographs
of the hands and/or feet should be obtained since
structural damage cannot be deduced by physical
examination alone. Arresting and preventing struc-
tural damage is a primary goal of therapy, and repeat
radiographic studies of sentinel or major involved
joints may be needed periodically.
Managed or coordinated multidisciplinary care
is efficacious in maintaining the function and produc-
tivity of patients with RA (16-24). Depending on the
patient’s problems, expertise from nursing, physical
and occupational therapy (25-29), social work, health
education, clinical psychology, vocational rehabilita-
tion (30), podiatry, and/or orthopedic surgery perspec-
tives may be needed. For example, patients with
active RA who have compromised joint range of
motion or function secondary to the disease benefit
from instruction by rehabilitation specialists on how to
protect their joints, maintain range of motion of their
joints, conserve energy, and strengthen their muscles.
A longitudinal treatment plan needs to be de-
veloped with the patient. The discussion should ad-
dress disease prognosis and treatment options, taking
into account the costs, adverse effects, expected time
for response, and monitoring requirements of pharma-
cologic agents, in addition to the patient’s preferences.
Expectations for treatment and potential barriers to
carrying out the recommendations should be dis-
cussed. Patient education is critical to engaging the
patient in an effective partnership for managing the
disease. Useful patient education materials are avail-
able from the Arthritis Foundation.
The aggressiveness and timing of the treatment
program require an assessment of prognosis. Poor
prognosis is suggested by earlier age at onset, high
titer of RF, elevated ESR, and swelling of >20 joints
(31). Extraarticular manifestations of RA, including
rheumatoid nodules, Sjogren’s syndrome, episcleritis
and scleritis, interstitial lung disease, pericardial dis-
ease, systemic vasculitis, and Felty’s syndrome, indi-
716
Table 2. Use of nonsteroidal antiinflammatory drugs for rheuma-
toid arthritis
Goal
Symptomatic relief of pain and swelling
Limitation
Unlikely to prevent damage
Factors for selecting drugs
Dosing regimen
Efficacy
Tolerance
costs
Patient’s age
Presence of comorbid disease(s)
Concurrent drugs
Patient preferences
Monitoring efficacy
Symptoms and signs of active synovitis
Monitoring toxicity*
* For symptoms and signs of toxicity, see the American College of
Rheumatology Guidelines for Monitoring Drug Therapy in Rheuma-
toid Arthritis (5).
cate a worse prognosis. These manifestations may
vary in severity and significance. Consultation with a
rheumatologist is advised for their treatment.
The history, joint examination, and functional
assessment are the primary tools used to assess prog-
nosis during the first 2 years of disease.
Drug treatment of rheumatoid arthritis
Nonsteroidal antiinflammatory drugs (NSAIDs).
The initial drug treatment of RA usually involves the
use of NSAIDs to reduce joint pain and swelling and
improve function (Table 2). NSAIDs have analgesic
and antiinflammatory properties but do not alter the
course of the disease or prevent joint destruction.
There are no significant differences in efficacy
among the NSAIDs, although there are some differ-
ences in the incidence of side effects. Salicylates are
inexpensive, and blood levels may be measured to
confirm that there has been an adequate antiinflamma-
tory dose and to assess compliance. The choice of
NSAID is based principally on cost, duration of ac-
tion, and patient preference (32). Analgesic effects of
salicylates and NSAIDs are prompt in onset, but
reduction of signs of inflammation may take up to 1-2
weeks.
To reduce gastrointestinal (GI) toxicity, pa-
tients should take NSAIDs with food, rather than on
an empty stomach. Patients with NSAID-induced GI
intolerance or toxicity may require the concomitant
use of GI-protective agents (e.g., the prostaglandin
ACR CLINICAL GUIDELINES COMMITTEE
analog misoprostol) (33,34). Use of GI-protective
agents when NSAID treatment is started should be
considered for elderly patients and patients with prior
peptic ulcer disease, GI bleeding, or cardiovascular
disease (33). Patients should be informed about the
potential symptoms of gastric irritation or bleeding,
with instructions to stop the medication and contact
the physician in the event of serious problems. Older
patients, patients with comorbid diseases (e.g., hyper-
tension, diabetes, congestive heart failure, renal im-
pairment, cirrhosis, or other states of renal hypoper-
fusion), and patients taking concurrent medications
that reduce renal blood flow (such as diuretics) must
be monitored carefully for renal insufficiency when
given NSAIDs. NSAIDs are associated with lower
rates of GI bleeding and cause fewer GI side effects
than antiinflammatory doses of non-enteric-coated
aspirin (35).
The frequency of some side effects may vary
among different NSAIDs. Combinations of 2 or more
NSAIDs should be avoided since they are no more
effective and may have additive adverse effects (32).
Disease-modifying antirheumatic drugs
(DMARDs). All patients whose RA remains active
despite adequate treatment with NSAIDs are candi-
dates for DMARD therapy (Table 3). Active RA may
lead to irreversible joint damage even in the early
months of the disease (9); while NSAIDs and gluco-
corticoids may alleviate symptoms, joint damage may
occur and progress. DMARDs have the potential to
reduce or prevent joint damage, preserve joint integ-
rity and function, and, ultimately, to reduce the total
costs of health care and maintain economic productiv-
Table 3. Use of disease-modifying antirheumatic drugs for rheu-
matoid arthritis
~~~~
Goal
Remission or optimal control of inflammatoryjoint disease
Limitations
May not prevent damage in spite of apparent clinical control
May not have lasting efficacy
May not be tolerated due to toxicity
Factors for selecting drugs
Convenience and cost of medication and monitoring for toxicity
Risk of adverse reactions, including frequency and seriousness
Physician estimate of efficacy and disease prognosis
Monitoring efficacy
Is disease in remission or optimally controlled?
Monitoring toxicity*
* For symptoms and signs of toxicity, see the American College of
Rheumatology Guidelines for Monitoring Drug Therapy in Rheuma-
toid Arthritis (5).
GUIDELINES FOR RA MANAGEMENT
Table 4. Disease-modifying antirheumatic drugs used in treatment of rheumatoid arthritis*
~~ ~
Approximate
time to
Drug benefit
Hydroxychloroquine 2 4 months
Sulfasalazine 1-2 months
Methotrexate 1-2 months
Injectable gold salts 3-6 months
Oral gold 4-6 months
Azathioprine 2-3 months
D-penicillamine 3-6 months
* GI = gastrointestinal; IM = intramuscular; elevated LITs = elevated results on liver function tests.
t For more detailed information on monitoring the symptoms and signs of toxicity, see the American
College of Rheumatology Guidelines for Monitoring Drug Therapy in Rheumatoid Arthritis (5).
ity of the patient with RA. These drugs include hy-
droxychloroquine (HCQ), sulfasalazine (SSZ), metho-
trexate (MTX), gold salts, D-penicillamine (DP), and
azathioprine (AZA).
Timing is critical. The initiation of DMARD
therapy should not be delayed beyond 3 months for
any patient with an established diagnosis who, in spite
of adequate treatment with NSAIDs, has ongoing joint
pain, significant morning stiffness or fatigue, active
synovitis, or persistent elevation of the ESR or CRP
level. Rheumatology consultation should be consid-
ered for confirmation of the diagnosis of RA and for
the decision regarding the initiation and selection of a
DMARD. The goal of treatment is to intervene in the
disease before joints are damaged. Any untreated
patient with persiqtent synovitis and joint damage
already documented by joint examination or radiogra-
phy should have DMARD treatment started promptly
to prevent or slow further damage.
DMARDs have common characteristics. All are
relatively slow acting, with a delay of 1 4 months
before a clinical response is evident. Efficacy cannot
be predicted for the individual patient, but up to
two-thirds of patients may have a response to these
agents. Each DMARD has specific toxicity that re-
quires careful monitoring. Detailed descriptions of
drug toxicity and recommendations for monitoring are
specified in the American College of Rheumatology
(ACR) Guidelines for Monitoring Drug Therapy in
717
Usual
maintenance
dose Toxicityt
200 mg twice Infrequent rash, diarrhea, rare retinal
daily toxicity
1,OOO mg Rash, infrequent myelosuppression, GI
twice or 3 intolerance
times daily
7.5-15 mg GI symptoms, stomatitis, rash, alopecia,
per week infrequent myelosuppression, hepa-
totoxicity, rare but serious (even life-
threatening) pulmonary toxicity
25-50 mg IM Rash, stomatitis, myelosuppression,
every 2 - 4 thrombocytopenia, proteinuria
weeks
3 mg daily or Same as injectable gold but less
twice daily frequent, plus frequent diarrhea
50-150 mg Myelosuppression, infrequent hepa-
daily totoxicity, early flu-like illness with
fever, GI symptoms, elevated LFTs
250-750 mg Rash, stomatitis, dysgeusia, proteinuria,
daily myelosuppression, infrequent but
serious autoimmune disease
Rheumatoid Arthritis (5). The decision to start a
DMARD must be preceded by a discussion with the
patient about the expectations of risks versus benefits
of the treatment.
Many factors influence the choice of a DMARD
for an individual patient (Table 4). From the patient’s
perspective, the convenience of administration of the
drug, the requirements of the monitoring program, the
costs of the medication and its monitoring, the time
until expected benefit, and the frequency and potential
seriousness of adverse reactions are important consid-
erations. The physician should also assess patient
factors such as compliance and comorbid diseases, the
severity and prognosis of the patient’s disease, and the
physician’s own confidence in administering and moni-
toring the drug.
It is not known which is the best initial DMARD
for patients with RA. Because of safety, convenience,
and cost, HCQ or S S Z is often the initial selection for
patients with milder disease. Generally well tolerated,
HCQ requires no laboratory monitoring, although pa-
tients need periodic ophthalmologic examinations for
early detection of reversible retinal toxicity (i.e., mac-
ulopathy manifested by decreased night vision or loss
of peripheral vision) (36-38). SSZ requires monitoring
(i.e., periodic CBC) for rare hematologic complica-
tions. Within 1-6 months, the response to these agents
should be apparent and the need for a change in
therapy may be determined.
718 ACR CLINICAL GUIDELINES COMMITTEE
Many rheumatologists select MTX as the initial
DMARD, especially for patients with severe disease
as evidenced by the presence of RF positivity, ero-
sions, or extraarticular manifestations. MTX is the
DMARD with the most predictable benefit. More than
50% of patients taking MTX continue the drug beyond
3 years, longer than any other DMARD (3843).
Disadvantages of MTX include its expense and the
need for laboratory monitoring. Stomatitis, nausea,
diarrhea, and perhaps alopecia from MTX use may
decrease with concomitant folic acid (44,45) or folinic
acid (46) treatment, without loss of efficacy. Liver
disease, renal impairment, significant lung disease, or
alcohol abuse are relative contraindications for MTX
therapy. The risk of liver toxicity is small, but liver
function must be monitored (47). The ACR guidelines
for monitoring liver toxicity in patients receiving MTX
state that liver biopsy should be performed in patients
who develop liver function blood test abnormalities
that persist during treatment with, or after discontin-
uation of, the drug (47). Rare but potentially serious
and even life-threatening pulmonary toxicity may oc-
cur any time with MTX at any dosage. Rarely, lym-
phoproliferative disorders may occur in patients taking
MTX (48), but the relationship to the medication is
unclear. This relationship is addressed in more detail in
the guidelines for monitoring drug treatment in RA (5).
Intramuscular gold treatment is effective (49-
5 l), but weekly intramuscular injections are required
for 22 weeks before less frequent maintenance dosing
is initiated. Monitoring for proteinuria, thrombocyto-
penia, and neutropenia should be performed prior to
each weekly injection. In patients receiving long-term
gold therapy (>6 months), toxicity monitoring may be
performed with every other injection. Although oral
gold is more convenient than injectable gold, there is a
long delay (up to 6 months) before benefit is evident,
and it is less efficacious (50,52).
DP is effective (50,51,53,54), but its use is
limited by an inconvenient dosing schedule (i.e., slow
increases in dosage) and infrequent but potentially
serious complications of autoimmune diseases such as
Goodpasture’s syndrome or myasthenia gravis. AZA,
a purine analog myelosuppressant, has demonstrated
benefit for controlling KA (50,51). Low-dose cyclo-
phosphamide is effective, but carcinogenic. Although
studies have documented the efficacy of cyclosporin A
in the treatment of RA, it has not yet received Food
and Drug Administration (FDA) approval for use in
RA (55,56), and its use is limited by cost and potential
renal toxicity.
For women of childbearing age, effective con-
traception is required when most DMARDs are pre-
scribed (5). The drug regimen will need modification if
the patient is or wishes to become pregnant, or if
breastfeeding is contemplated (5).
Whether DMARDs should be given in a sequen-
tial or additive manner for patients with persistently
active disease remains controversial (31,5137). Rheu-
matology referral is strongly recommended for pa-
tients with refractory disease in whom combination
DMARDs are considered. Some rheumatologists
initiate treatment with a combination of several
DMARDs and gradually withdraw the drugs as disease
control is achieved (58). Most rheumatologists use
combinations of DMARDs to treat patients who have
had a partial response to a DMARD or whose disease
has been refractory to different individual DMAKDs.
Table 5. Use of glucocorticoid therapy for rheumatoid arthritis
Local injection
Goals
Treatment of the most symptomatic joints early in the disease
course
Treatment of flares in 1 or a few joints
Recovery of lost joint motion
Limitations
Local therapy, but disease is a systemic process
Only temporary benefit if disease is not controlled
systemically
Factors for selecting drugs
Need for long-acting preparation
Concentration varies with size of joint being injected
Monitoring efficacy
Improvement in synovitis, restoration of range of motion
Monitoring toxicity*
Avoid repetitive injections into same joint more than once
every 3 months
Low-dose oral (510 mg prednisone daily)
Goalst
Minimizing disease activity while awaiting DMARD response
Decreasing disease activity for a limited time period (i.e., a
short course for flares or special life events)
Control of active disease in spite of optimal NSAID treatment
and trials of DMARDS (i.e., unacceptable discomfort or
limitations of function)
Limitation
Damage may progress despite symptomatic control
Factors for selecting drugs
Initial and maintenance dose selection critical
Monitoring efficacy
Symptoms and signs of active synovitis
Improvement in function
Monitoring toxicity*
* For symptoms and signs of toxicity, see the American College of
Rheumatology Guidelines for Monitoring Drug Therapy in Rheuma-
toid Arthritis ( 5 ) .
t DMARD = disease-modifying antirheumatic drug; NSAID =
nonsteroidal antiinflammatory drug.
GUIDELINES FOR RA MANAGEMENT
The most commonly used combinations are MTW
HCQ, MTWSSZ, and gold/HCQ (59-63). Studies are
needed to determine the most effective combination of
DMARDs for use in RA.
The majority of patients with active RA receive
an NSAID and at least I DMARD, with or without
low-dose oral glucocorticoids. If disease remission is
observed, regular NSAID or systemic glucocorticoid
treatment may no longer be needed. DMARDs control
RA but usually do not cure the disease. For that
reason, if remission or optimal control of RA is
achieved with a DMARD, it should be continued at a
maintenance dosage. Discontinuing a DMARD may
reactivate disease or cause a “rebound flare,” with no
assurance that disease control will be reestablished
upon resumption of the medication.
Glucocorticoids. Low-dose oral glucocorticoids
(510 mg prednisone daily or equivalent) and local
injections of glucocorticoids are highly effective for
relieving symptoms in patients with active RA (Table
5 ) . Low-dose glucocorticoids appear to slow the rate
ofjoint damage (64). The adverse effects of systemic
glucocorticoids, especially when taken in higher doses
for extended periods of time, limit their use, however.
When administered by an experienced physician, glu-
cocorticoid injection of joints and periarticular struc-
tures is safe and effective. Injecting 1 or a few of the
most involved joints in a patient early in the course of
RA may provide local and even systemic benefit. The
effects are sometimes dramatic, but may be tempo-
rary. Prompt improvement from intraarticular gluco-
corticoids helps to instill confidence that treatment can
be effective. A patient who has flare in 1 or a few joints
can be treated successfully by injection of the flaring
joint or joints, without requiring a major change in the
prescribed regimen. Local glucocorticoid injections
may also allow the patient to participate more fully in
rehabilitation programs to restore lost joint function.
Not all joint flares in RA are from the disease.
Joint infection must be considered and ruled out
before local glucocorticoid injection. In general, the
same joint should not be injected more than once
within 3 months. The need for repeated joint injections
in the same joint or for multiple joint injections indi-
cates the need to reassess the adequacy of the overall
treatment program.
The adverse effects of systemic glucocorticoids
increase with higher doses and longer duration of
treatment. For uncomplicated RA, prednisone should
not be given at a dosage higher than 10 mg daily. Every
effort should be made to limit its use to a short course
or, if maintenance treatment is necessary, to use the
lowest possible dosage.
719
Table 6. Monitoring rheumatoid arthritis activity
~~~ ~ ~~
Each visit: evaluate for subjective and objective evidence of
active disease
Degree of joint pain
Duration of AM stiffness
Severity of fatigue
Presence of actively inflamed joints on examination
Limitation of function
Periodically: evaluate for disease activity or progression
Evidence of disease progression on physical examination (loss
of motion, instability, malalignment, and/or deformity)
Erythrocyte sedimentation rate or C-reactive protein elevation
Progression of radiographic damage of involved joints
Other parameters for assessing response to treatment (outcomes)
Physician global assessment of disease activity
Patient global assessment of disease activity
Tender and swollen joint count
Pain assessment
Functional status assessment
Low-dose oral glucocorticoids may benefit the
patient during the period before a DMARD has gained
its full effect and at times when the disease is severe
enough to affect the patient’s function, sleep, or ability
to work. Glucocorticoids are also used for patients
with refractory RA in whom trials of NSAIDs and
DMARDs have failed. For patients receiving systemic
glucocorticoids who exhibit stable or improving dis-
ease, tapering of the dosage and eventual discontinu-
ation of the medication should be attempted.
Surgery
Even if joint inflammation is successfully con-
trolled or eliminated with medication, patients with
chronic RA may be symptomatic from joint damage.
If. in spite of optimal medical treatment, the patient
has unacceptable pain and/or limitation of function
because of structural joint damage, surgery should be
considered. The most successful surgical procedures
for RA are carpal tunnel release, resection of the
metatarsal heads, and total hip and total knee arthro-
plasty . Outcomes of surgery and complication rates
are related to the volume of surgery (i.e., number of
surgeries performed annually at an institution), timing
of surgery, experience of the surgeon, patient’s pre-
operative medical status, and postoperative manage-
ment and rehabilitation. Occupational and physical
therapy expertise is an important component of restor-
ing and optimizing function, especially after total knee
arthroplasty, shoulder surgery, and hand surgery.
Monitoring rheumatoid arthritis activity and the
safety and adequacy of the treatment program
Monitoring of the patient’s illness and his or her
response to treatment varies with disease severity,
720 ACR CLINICAL GUIDELINES COMMITTEE
activity, and the drug regimen used, but all patients
need to be followed up indefinitely. Patients whose
disease is in remission may be seen semiannually, with
the frequency of laboratory or other monitoring dic-
tated by the drug program. Patients with early disease,
flares, or persistently active disease require more
frequent physician visits until disease control is estab-
lished.
At each visit the physician must assess whether
the disease is active (Table 6). Symptoms of inflam-
matory (as contrasted with mechanical) joint disease,
prolonged morning stzness, fatigue, and active syno-
vitis seen on joint examination indicate active disease
and the need to consider changing the treatment
program. The joint examination may not adequately
reflect disease activity and structural damage. There-
fore, periodic measurements of ESR or CRP and
functional status and radiographic examinations of
involved joints should be performed. Functional status
assessment may be performed with questionnaires
such as the Arthritis Impact Measurement Scales (65)
or the Health Assessment Questionnaire (66).
If the patient’s disease is active or progressing,
other options, including consultation with a rheuma-
tologist, should be considered. If disease activity is
confined to 1 or a few joints, local glucocorticoid
injection may help. Change in the drug regimen may be
considered, especially increasing DMARD dosage,
changing the DMARD, or adding a DMARD. Patients
with severe symptoms may need to start taking or to
increase the dosage of systemic glucocorticoids. Ac-
tive joint disease may be aggravated by physical
activity; consultation with a physical therapist, occu-
pational therapist, and/or vocational counselor should
be considered. Periods of rest, time off from work,
changes in occupation, or stopping work may be
necessary. For symptoms that are mechanical, surgi-
cal options need to be explored.
Refractory rheumatoid arthritis
RA may run a resistant course, with progres-
sive disability and joint damage. Rheumatology re-
ferral is strongly recommended for patients with re-
fractory disease. Medications which are not yet
FDA-approved for treating RA (such as cyclosporine)
may be useful. Some patients may be candidates for
treatment with investigational pharmacologic or bio-
logic agents. Patients with refractory RA frequently
require treatment with systemic glucocorticoids and/or
analgesics. With a chronic disease like RA, every
effort should be made to avoid creating dependency
upon narcotic analgesics, although some use may be
justified. The longitudinal management of the patient
with RA depends on mutual trust and confidence
between the patient and hidher health care providers,
who are expected to be supportive, empathetic, and
knowledgeable.
The responsibilities of primary and specialty care
physicians
Depending on the health care setting, the ma-
jority of the care of the patient with RA may be
provided by a single physician (primary care physi-
cian, rheumatologist, or rheumatologist who also pro-
vides primary care), or the responsibility may be
shared. The role of the primary care physician is to
recognize and diagnose RA at its onset and to ensure
that the patient receives timely treatment before per-
manent joint damage has occurred. The rheumatolo-
gist should provide support and consultation to the
patient and his or her primary care physician in the
diagnosis and treatment of RA. Since the level of
training and experience in diagnosing and caring for
RA varies among primary care physicians, the respon-
sibility for accurate diagnosis and monitoring of RA
activity and/or drug toxicity may appropriately be
assigned to a rheumatologist. If the care of a patient
with RA is to be shared, an explicit plan for monitoring
RA disease activity (Table 6) and/or drug toxicity
needs to be formulated. The patient’s preference may
be the most important factor in deciding which physi-
cian(s) assume responsibility for care.
General health maintenance
A general health maintenance strategy should
be developed and responsibility coordinated among
the patient’s health care providers. Routine prevention
measures should be recommended and risk factors
modified. The lifespan of a patient with RA may be
shortened by infection, pulmonary disease, renal dis-
ease, or GI bleeding (30). Patients at risk for GI
bleeding may benefit from avoidance of gastric irri-
tants and the use of gastroprotective drug therapy. For
patients at risk for osteoporosis (by history, inactivity,
and/or glucocorticoid treatment), evaluation with bone
densitometry at baseline and treatment with calcium
supplementation, vitamin D (400 units daily), bisphos-
phonates, or calcitonin should be considered. Estro-
gen replacement therapy should be discussed with
postmenopausal women.
Summary
RA is a chronic progressive polyarthritis (with
varying systemic features) associated with substantial
GUIDELINES FOR RA MANAGEMENT
disability and economic losses. Successful treatment
to limit joint damage and functional loss requires early
diagnosis and timely initiation of disease-modifying
agents. The goal of treatment is to arrest the disease
and to achieve remission. Although remission rarely
occurs, patients may still benefit from pharmacologic,
nonpharmacologic, and if necessary, surgical inter-
ventions. Optimal longitudinal treatment requires
comprehensive coordinated care and the expertise of a
number of providers. Essential components of man-
agement include 1) establishment of the diagnosis of
RA (versus other forms of polyarthritis), 3) systematic
and regular evaluation of disease activity, 3) patient
educationh-ehabilitation interventions, and initial
treatment with NSAIDs, 4) use of DMARDs, 5 ) pos-
sible use of local or low-dose oral glucocorticoids, 6)
minimization of the impact on the individual’s func-
tion, 7) assessment of the adequacy of the treatment
program, and 8) general health maintenance.
ACKNOWLEDGMENTS
The authors thank Drs. Mary Charlson, Doyt Conn,
John Eisenberg, John Esdaile, Christine Evelyn, Herbert
Kaplan, Donald Middleton, Daniel Rahn, S h a m Ruddy,
Burton Sack, Michael Schiff, Terence Starz, Bruce Trimble,
Michael Weinblatt, Jeffrey Wilson, and the American Col-
lege of Rheumatology Committee on Rheumatologic Care
for their thoughtful critique. We also thank Donna Cosola,
Steven Echard, Jacqueline Mazzie, and Mary Scamman for
technical assistance with the preparation of the manuscript.
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