Session Details

Patient ID: MS116-01

Patient is a 45−year−old woman diagnosed with RA nearly 2 years ago. She

presents today experiencing major joint symptoms with swelling, stiffness, and pain
on movement in the hands, wrists, knees, ankles, and feet. She has about 45
minutes of morning stiffness and is feeling very tired and worn out, but denies
symptoms of depression.

Case Summary
This patient with rheumatoid arthritis (RA) has had persistent symptoms and
progressive joint damage despite efforts to treat her with conventional DMARDs
including MTX. Despite these interventions, the disease has remained highly
active, and a change in therapy is warranted.

Several therapeutic possibilities can be considered. First of all, an anti−TNF agent

(such as adalimumab, etanercept, infliximab, golimumab or certolizumab) may be
started. This approach is consistent with ACR guidelines. Should an agent with a
different mechanism of action become necessary or desirable, three biologics with
other mechanisms could be considered in this patient: abatacept (a blocker of
T−cell costimulation), rituximab (a B−cell depleting agent) and tocilizumab (an IL−6
antagonist).

The synthetic targeted agent tofacitinib (a JAK−inhibitor), may be a consideration

as well. The choice between these other options above remains empirical for now;
there have been insufficient or no head−to−head trials comparing many of them
directly.

The patient should be followed closely with at least 1 of the recommended tests of
RA activity, such as the CDAI, and a sensitive imaging study, such as
Musculoskeletal Ultrasound exams. This is important since some patients who
appear clinically and even by severity scores to be in remission may have evidence
of ongoing inflammatory changes using sonography.

For the patient on whom this case was based, the faculty author considered all
options and discussed them extensively with the patient, who requested that
methotrexate be stopped if possible. As such, biologics that would not be an option
without concomitant methotrexate (according to FDA package inserts) would
include infliximab, golimumab, and rituximab, making the following amended list:
  adalimumab

 etanercept

 certolizumab

Should the patient progress or not reach their target on an anti−TNF agent and
methotrexate is not being given concomitantly, then future options would include

 abatacept

 tocilizumab

 Finally, tofacitinib may be given with or without methotrexate.

Successful treatment of RA requires a multidisciplinary approach. The importance

of physical therapy, screening for depression and managing it, and yearly
immunizations, as well as patient education and counseling about RA, the
importance of drug adherence, and which side effects and toxicities to watch for
are also important.

Rheumatoid arthritis (RA) is a chronic autoimmune disease that damages the lining of the
joints causing swelling, cartilage and bone erosion, and joint deformity. RA affects joints on
both sides of the body, and may also affect the skin, eyes, lungs, and blood
vessels. 125 RA occurs more often in women than in men, and the rate of onset is highest
among people in their 60s. An estimated 1.5 million adults in the United States have RA. 5

A patient with suspected RA should have a thorough physical exam where the clinician
examines each joint to check for pain, swelling, warmth, and limited range of motion.
Recent European League Against Rheumatism (EULAR) recommendations state that
conventional radiography, ultrasound, or magnetic resonance imaging (MRI) can be used
to improve the certainty of a diagnosis when there is diagnostic doubt. If there is clinical
suspicion that a patient's cervical spine is involved, then the stability of the cervical spine
should be monitored using lateral X−rays in flexed and neutral positions. If the X−ray is
positive, then the clinician should order an MRI. 7

TREATMENT

Treating to Target

Structural damage can happen early in the disease course of RA, but early treatment can
reduce inflammation and limit structural damage. In 2010, treat−to−target
recommendations in RA were formulated, and clinicians were encouraged to target
remission or low disease activity in their patients with RA. 20 Recently, an international
task force issued updated treat−to−target recommendations. The task force created 4
overarching principles to guide treatment: 1) treatment must be based on shared
decision−making between patient and rheumatologist, 2) the primary goal of treatment is
to maximize long−term quality of life, 3) controlling inflammation is the most important way
to achieve treatment goals, and 4) treatment to target means measuring disease activity
and adjusting therapy to optimize outcomes. 21

Imaging

Plain radiographs are used to evaluate patients with RA, and they allow clinicians to
assess disease progression if serial images are available. However, early damage caused
by RA cannot be seen on X−ray. 22

Ultrasound and MRI are better than clinical examination in detecting joint inflammation and
are more useful than conventional radiographs in monitoring disease activity. 7 Both of
these imaging techniques can detect synovitis and inflammation in the lining of the joints,
as well as tendon abnormalities. MRI can also detect bone marrow edema, which is a
predictor for the development of bone erosions. 3 The major advantage of these types of
imaging over X−rays is that joint damage can be detected earlier in the disease
course. 22 MRI may also be useful in monitoring patients who are in remission. In a study
of 56 patients in sustained clinical remission, 96.4% were found to have synovitis on MRI
examination. In addition, those patients with erosion progression had significantly higher
bone marrow edema scores, and this may explain why some patients in remission
continue to have progressing bone erosions. This study was limited by the small number of
participants. 11 MRIs are much more expensive than X−rays and require an experienced
radiologist to read them, which may limit their use. 3

Rheumatologists often have access to Doppler ultrasound in their offices to for both
diagnostic and therapeutic applications (to guide joint aspirations and injections).
Musculoskeletal ultrasound is used to examine disease activity in patients with
RA. 3 Ultrasonography can be augmented with amplitude color Doppler (ACD) imaging, a
technique that was originally developed to improve vascular sonography. ACD imaging
has been used in RA patients to evaluate hyperemia in the tissues surrounding the
inflamed joints. Synovial hyperemia is a fundamental feature in RA and is common in the
tendon sheath as well. It is highly likely that synovial hyperemia is responsible for
periarticular demineralization viewed on X−rays, a classic feature of RA. It is thought that
this demineralization occurs in proportion to joint−destructive disease activity. 22Currently,
data are lacking as to how exactly RA should be measured on ultrasound and how many
joints must be examined.3
Imaging Guidelines

In 2013, recommendations for the use of imaging in RA were formulated by a EULAR task
force. EULAR recommends that X−rays of the hands and feet be used first to detect
damage. However, if X−rays do not show damage in a patient with suspected RA, then
ultrasound and MRI should be used. EULAR recommends periodic X−rays of the hands
and feet to monitor joint damage. MRI can show changes in joint damage more precisely
and may also be used to monitor disease progression. Finally, even when a patient is in
remission, ultrasound and MRI can detect persistent inflammation predictive of future joint
damage. The recommendations do not address the detection of joint space narrowing, but
mention its impact on a patient's functional status. EULAR states that this will be the
subject of future research. 7

Measurement of Disease Activity

To assess the effectiveness of treatment, clinicians must be able to assess disease activity
regularly. 19 Swollen joint counts correlate with joint damage progression, while tender
joint counts correlate with physical function; therefore, instruments that include both
measurements are preferred. Furthermore, formal joint counts are included in
treat−to−target recommendations. 20 There are 3 assessments available that include both
swollen and tender joint counts.

The Disease Activity Score 28 (DAS28) includes the provider's assessment of 28 joints for
tenderness and swelling, a general health assessment on a visual analogue scale, and
either an erythrocyte sedimentation rate (ESR) or C−reactive protein (CRP)
measurement. 2 The formula used to compute DAS28 yields a score from 0−9.4, with
remission being defined as <2.6. 19 ESR and CRP are weighted more heavily in the
DAS28 formula, such that therapies that affect the acute phase response (eg, those that
inhibit the interleukin−6 pathway) will show exaggerated remission rates. 20

The Clinical Disease Activity Index (CDAI) includes the provider's assessment of 28 joints
for tenderness and swelling; the patient's global assessment of disease activity; and the
provider's global assessment of disease activity. The sum of these scores will range from
0−76. Remission is ≤2.8, low activity is 2.9−10, moderate activity is 10.1−22, and high
activity is 22.1−76. 2

The Simplified Disease Activity Index (SDAI) includes the same components as the CDAI,
but also includes a CRP measurement. The sum of all the components yields a score from
0−86. Remission is ≤3.3, low activity is 3.4−11, moderate activity is 11.1−26, and high
activity is 26.1−86. 2 SDAI and CDAI remission have been shown to be associated with no
or minimal joint involvement, even by ultrasound, and these remission states have also
been shown to best reflect quality of life and reduction of cardiovascular risk. SDAI and
CDAI improvement criteria are simple enough to use in both clinical practice and clinical
trials: a reduction of 50% in the score indicates minor improvement (ACR20 response), a
reduction of 70% in the score is moderate improvement (ACR50 response), and a
reduction of 85% constitutes major improvement (ACR70 response). 20

Pharmacologic Agents

Disease−Modifying Antirheumatic Drugs (DMARDs)

DMARDs are the usual first−line treatment for RA. Methotrexate (MTX) is the most
common DMARD. It is generally well tolerated, even during long−term use. Adverse
effects include rash and stomach upset, but taking folic acid may reduce some of the
adverse effects. Leflunomide works as well as MTX, and may be used in combination with
MTX. In some patients, leflunomide may cause diarrhea, forcing treatment discontinuation.
Leflunomide should not be used during pregnancy. Hydroxychloroquine is typically used in
mild RA. It may cause rare eye problems (maculopathy), so patients should have yearly
eye exams. Sulfasalazine tablets are also used for mild cases of RA and may be
combined with other DMARDs. 23 ACR guidelines recommend that patients taking
leflunomide, MTX, or sulfasalazine have laboratory monitoring every 2 to 4 weeks during
the first 3 months of therapy, every 8 to 12 weeks during months 3−6 of therapy, and every
12 weeks after 6 months of therapy. For patients taking hydroxychloroquine, no routine
laboratory monitoring is required after baseline tests are performed (except for periodic
ophthalmologic exams). 19

Anti−Tumor Necrosis Factor (Anti−TNF) Biologics

Anti−TNF agents are injected intravenously or subcutaneously and neutralize TNF, an

immune molecule that causes inflammation leading to joint damage. Currently, 5 of these
agents have been approved by the US Food and Drug Administration (FDA) to treat RA.
They are often used in combination with MTX and are thought to have a better adverse
effect profile than other treatments. They may also work more quickly than traditional
DMARDs. 23 Patients may also develop anti−drug antibodies to these drugs, especially
those that are monoclonal antibodies, leading to decreased serum drug levels and
diminished treatment effectiveness. 4 Based on available evidence, clinicians should not
administer live vaccines to patients who are receiving anti−TNF therapy. 19 Clinicians
should monitor patients for signs and symptoms of infection including tuberculosis and
invasive fungal infections. 19 Targeted TNFα inhibitor use may be associated with heart
failure (HF); therefore, the ACR treatment guidelines prefer other biologic DMARDS for
use in patients with HF.

Adalimumab is a fully human antibody that may be taken without MTX. 13 It is

administered subcutaneously. The usual dosage is 40 mg every other week, but patients
who are not taking MTX may benefit from taking 40 mg every week. Adalimumab carries a
black box warning for serious infections and malignancy. Common adverse effects include
infections, injection site reactions, headache, and rash. Adalimumab should not be used
concomitantly with anakinra or abatacept. 9

Certolizumab pegol binds to TNF cells to reduce inflammation; it may be given with or
without MTX. 13It is administered subcutaneously; the initial dose is 400 mg and this dose
is repeated at weeks 2 and 4. Afterward, patients receive 200 mg every other week.
Clinicians may also consider maintenance dosing where patients receive 400 mg every 4
weeks. Certolizumab carries a black box warning for serious infections and malignancy.
Common adverse events include upper respiratory tract infection, rash, and urinary tract
infection. 6

Etanercept is a manufactured protein that is created by fusing 2 human proteins

together. 13It is administered subcutaneously once weekly, and the usual dosage for RA is
50 mg once weekly with or without MTX. Etanercept carries a black box warning for
serious infections and malignancy. Common adverse events include infections and
injection site reactions. 8

Infliximab is a manufactured antibody that must be administered intravenously over a

period of at least 2 hours. In combination with MTX, the usual dose is 3 mg/kg at 0, 2, and
6 weeks. Treatment is then given every 8 weeks. Some patients may do better when the
dose is increased up to 10 mg/kg or given as often as every 4 weeks. Infliximab carries a
black box warning for serious infections and malignancy and is contraindicated at doses
>5 mg/kg in patients with moderate or severe HF. Common adverse events include
infections, injection site reactions, headache, and abdominal pain.1513

Golimumab is a fully human antibody indicated for moderate to severe RA in combination

with MTX. It is injected subcutaneously once each month, and the usual dose is 50 mg.
Golimumab carries a black box warning for serious infections and malignancy. The most
common adverse events are upper respiratory tract infection, nasopharyngitis, and
injection site reactions. Golimumab should not be given with abatacept or anakinra. 18 13

Non−Anti−TNF Biologics

Non−anti−TNF agents have other therapeutic targets within the immune system. Patients
who are receiving non−anti−TNF biologic therapy should not receive live vaccines. 19

Rituximab binds to CD20 on the surface of certain B cells and causes cell lysis. The
resulting depletion of B cells reduces inflammation in the body. Rituximab is used in
combination with MTX in patients who have not responded to ≥1 anti−TNF agents.
Rituximab carries a black box warning for fatal infusion reactions, severe mucocutaneous
reactions, hepatitis B reactivation, and progressive multifocal leukoencephalopathy. The
normal treatment course comprises 2 intravenous infusions of 1000 mg each separated by
2 weeks. A treatment course is typically administered every 24 weeks. Patients should
receive 100 mg of methylprednisolone intravenously 30 minutes before each rituximab
infusion. The most common adverse events are upper respiratory tract infection,
nasopharyngitis, and urinary tract infection. Patients should be advised to avoid becoming
pregnant while taking rituximab and for 12 months after completing treatment. 17

Tocilizumab is a biologic directed against the interleukin−6 receptor and is used for
patients who have not responded to treatment with ≥1 DMARDs. It may be used alone or
in combination with MTX or other DMARDs. For intravenous dosing (whether administered
as monotherapy or in combination with other DMARDs), 4 mg/kg is given every 4 weeks
and can be increased to 8 mg/kg every 4 weeks depending on how the patient responds to
the medication. For subcutaneous use, the normal dose is 162 mg for patients weighing
<100 kg. This dose is given every other week and may be increased to every week
depending on patient response. Patients weighing >100 kg should receive 162 mg
subcutaneously every week. Tocilizumab carries a black box warning for serious
infections. Lipid perturbations and cytopenias are also seen. Common adverse events
include upper respiratory tract infection, nasopharyngitis, headache, and
hypertension. 1 Patients receiving tocilizumab need regular monitoring of complete blood
counts (CBC) and lipids.

Abatacept is a selective T cell costimulation modulator. It prevents the activation of T cells

to suppress the immune response. It may be used alone or with other non−anti−TNF
agents. For some patients, clinicians may use an intravenous, weight−based loading dose
(ie, 10 mg/kg). The normal dose is 125 mg given subcutaneously each week. Common
adverse reactions are headache, upper respiratory infections, nasopharyngitis, and
nausea. Abatacept use is associated with a risk of exacerbation of COPD. 16 14

Other Therapies

Tofacitinib is a janus kinase (JAK) inhibitor and is often used in patients who are no longer
responding to treatment with MTX. It may be used in combination with MTX or other
DMARDs but should not be used with biologics. The recommended dose is a 5−mg pill
taken twice daily, or 11 mg once daily. Cytopenias, lipid perturbations, and rare intestinal
perforations have been described with tofacitinib. Tofacitinib carries a black box warning
for serious infections and malignancy. Common adverse events include upper respiratory
infections, headache, diarrhea, and nasopharyngitis.24 23 Patients receiving tofacitinib
need regular monitoring of complete blood counts and lipids.

American College of Rheumatology (ACR) Treatment Recommendations

The 2015 ACR Guideline for the Treatment of RA provides recommendations for treating
patients with symptomatic early RA (defined as disease duration of <6 months) as well as
established RA. For both early and established RA, the most important recommendation is
that clinicians should use a treat−to−target strategy regardless of disease activity level.

For early RA, if disease activity is low and the patient has never taken a DMARD, then
DMARD monotherapy (preferably MTX) is the best option. If disease activity is moderate
or high and the patient has never taken a DMARD, then DMARD monotherapy is
preferred. If the patient's disease activity is still moderate or high after DMARD
monotherapy (with or without glucocorticoids), the ACR recommends a combination of
DMARDs or an anti−TNF biologic or a non−anti−TNF biologic (with or without MTX), rather
than continuing DMARD monotherapy. If disease activity remains moderate or high, the
ACR recommends anti−TNF agent monotherapy over tofacitinib monotherapy or an
anti−TNF agent plus MTX over tofacitinib plus MTX. Finally, the ACR recommends adding
low−dose glucocorticoids when disease activity remains moderate or high despite DMARD
or biologic therapy as well as for short−term use during disease flares. 19

For established RA, if disease activity is low and the patient has never taken a DMARD,
then DMARD monotherapy (preferably MTX) is preferred. If disease activity is moderate or
high and the patient has never taken a DMARD, then DMARD monotherapy (using MTX)
is preferred over tofacitinib and over combination DMARD therapy. If disease activity is still
moderate or high after DMARD monotherapy, the ACR recommends a combination of
traditional DMARDs or adding an anti−TNF agent or a non−anti−TNF biologic or tofacitinib
(with or without MTX), rather than continuing DMARD monotherapy.

If disease activity remains moderate or high in patients who are taking anti−TNF therapy,
but not DMARDs, the ACR recommends adding 1 to 2 DMARDs to the patient's anti−TNF
regimen. For patients whose disease activity is still moderate to high while taking a single
anti−TNF agent, clinicians should use a non−anti−TNF biologic (with or without MTX)
rather than another anti−TNF agent (with or without MTX). For patients taking a single
non−anti−TNF biologic whose disease activity is still moderate to high, clinicians should
use another non−anti−TNF biologic (with or without MTX) rather than tofacitinib (with or
without MTX). If disease activity is still moderate to high despite ≥2 sequential anti−TNF
agents, first use a non−anti−TNF biologic (with or without MTX) rather than an anti−TNF
agent or tofacitinib (with or without MTX).

If disease activity remains moderate to high after multiple anti−TNF agents, use tofacitinib
(with or without MTX) over another anti−TNF agent (with or without MTX) if a
non−anti−TNF biologic cannot be used. The ACR recommends adding short−term,
low−dose glucocorticoids when disease activity remains moderate or high despite
DMARD, anti−TNF, or non−anti−TNF biologic therapy and for short−term use during
disease flares. Once the patient is in remission, taper DMARD, anti−TNF, non−anti−TNF,
or tofacitinib therapy, but do not discontinue all RA therapies. If disease activity is low,
continue DMARD, anti−TNF, non−TNF biologic, or tofacitinib therapy. 19

Other Areas of Concern

Before beginning biologic or tofacitinib therapy, patients should be tested for tuberculosis
(TB). If there is no latent or active infection, treatment can begin. Patients with risk factors
for TB infection should be screened annually. If the TB test is positive, the patient should
have chest radiography, and possibly sputum cultures, to determine if the infection is
active or latent. If the TB infection is latent, the patient should receive at least 1 month of
treatment for latent TB before resuming RA therapy. If the TB infection is active, the
patient must complete a treatment regimen for active TB before resuming RA therapy. 19

The ACR Guideline recommends that patients recently diagnosed with RA receive the
pneumococcal, influenza (intramuscular), hepatitis B, human papilloma, and herpes zoster
vaccines before beginning any therapy. Patients who are already taking RA treatment can
receive the pneumococcal, influenza (intramuscular), hepatitis B, and human papilloma
vaccines. 19

Clinical Guidance
Therapies

Ibandronate

According to ACR guidelines, use of a bisphosphonate or teriparatide is

reasonable due to this patient’s current and possible long-term reliance
on 5 mg of prednisone daily.

Adalimumab

Adalimumab would be a suitable choice whether used as monotherapy

without methotrexate or as dual therapy with methotrexate.

calcium-vitamin D

Calcium with vitamin D treatment is reasonable for this patient. Risks for
osteoporosis include smoking, inadequate calcium and vitamin D intake,
expected ongoing prednisone use, and RA itself (which can lead to
premature osteoporosis).
Prednisone

Many patients with RA are functionally dependent on glucocorticoids and

continue them long term. Recent evidence suggests that low-dose
glucocorticoids slow the rate of joint damage and, therefore, appear to
have disease-modifying potential. Joint damage may increase on
discontinuation of glucocorticoids. The benefits of low-dose systemic
glucocorticoids, however, should always be weighed against their
adverse effects (AEs). The AEs of long-term oral glucocorticoids at
moderate or high doses include osteoporosis, hypertension, weight gain,
fluid retention, hyperglycemia, cataracts, and skin fragility, as well as the
potential for premature atherosclerosis. To what extent these risks are
also present when given at low doses (for example, 5 mg daily) remains
somewhat unclear. Nonetheless, these kinds of AEs should be
considered and discussed with the patient before glucocorticoid therapy is
begun.

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Folic Acid

If the clinician wishes to continue this patient's MTX as part of a treatment

plan, her folic acid should be continued, too. Stomatitis, nausea, diarrhea,
and alopecia caused by MTX may decrease with concomitant folic acid or
folinic acid treatment without significant loss of efficacy.

Drug Interactions

ibandronate + calcium carbonate (calcium-vitamin D): ADJUST

DOSING INTERVAL: Products containing aluminum, calcium,
magnesium and other polyvalent cations such as antacids or vitamin with
mineral supplements are likely to interfere with the gastrointestinal
absorption of oral bisphosphonates. For example, the bioavailability of
tiludronate has been shown to decrease 80% during simultaneous
administration with calcium, and 60% when aluminum- or magnesium-
containing antacids were administered one hour before tiludronate.
MANAGEMENT: Antacids or other oral medications containing aluminum,
calcium, magnesium and other polyvalent cations should be administered
at least 30 minutes after the bisphosphonate dose.
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predniSONE + calcium carbonate (calcium-vitamin D): Antacids and
agents with acid-neutralizing effects may impair the absorption of
dexamethasone, prednisolone, prednisone, and other corticosteroids,
although data from published studies are somewhat conflicting. The
mechanism of interaction and clinical significance are unknown. No
particular intervention is necessary during concomitant therapy with these
agents, but clinicians should be aware of the potential for interaction.

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predniSONE + adalimumab: MONITOR CLOSELY: The use of tumor
necrosis factor (TNF) blockers with other immunosuppressive or
myelosuppressive agents may increase the risk of infections. Serious
infections and sepsis, including fatalities, have been reported with the use
of TNF blockers, particularly in patients on concomitant
immunosuppressive therapy. Agents that may be significantly myelo- or
immunosuppressive include antineoplastic agents, radiation, zidovudine,
linezolid, some antirheumatic agents, high dosages of corticosteroids or
adrenocorticotropic agents (greater than 10 mg/day to 1 mg/kg/day,
whichever is less, of prednisone or equivalent for more than 2 weeks),
and long-term topical or inhaled corticosteroids. Concomitant use of TNF
blockers with other immunosuppressants such as azathioprine or
mercaptopurine may also increase the risk of a rare and often fatal cancer
of white blood cells known as hepatosplenic T-Cell lymphoma (HSTCL),
which has primarily been reported in adolescent and young adult males
receiving treatment for Crohn's disease or ulcerative colitis. Cases of
HSTCL have also occurred during use of these agents alone. Because
individuals with rheumatoid arthritis, Crohn's disease, ankylosing
spondylitis, psoriatic arthritis, or plaque psoriasis may be more likely to
develop lymphoma than the general population, it is difficult to assess the
added risk of TNF blockers, azathioprine, and/or mercaptopurine.
MANAGEMENT: Patients receiving a TNF blocker alone or with other
immunosuppressive or myelosuppressive agents should be monitored
closely for the development of infections. TNF blocker therapy should be
discontinued if a serious infection or sepsis occurs. Close monitoring for
signs and symptoms of HSTCL (e.g., splenomegaly, hepatomegaly,
abdominal pain, persistent fever, night sweats, weight loss) is also
recommended during use of TNF blockers, particularly in combination
with other immunosuppressants such as azathioprine and
mercaptopurine.

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Tests

Complete Blood Count (CBC) w/ Differential

Ordering a CBC may be a suitable option. Patients on antirheumatic

therapy such as MTX must be monitored periodically for side effects
including cytopenias. This is even more important when the underlying
disease is highly active, which can also be associated with cytopenias.
This patient has a moderate anemia of chronic disease that also requires
monitoring.

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Missed Test: Musculoskeletal Ultrasound (MSKUS)

Ultrasound examination of the joints is an optional imaging test for this

patient at today's visit. Ultrasound is used to complement the physical
examination and other imaging modalities. It provides a relatively quick
and easy assessment of inflammation in multiple joints and can help
identify joint effusions, synovitis, and boney erosions of RA that are not
seen with conventional radiography. However, it is not critically important
in this present scenario.

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Rheumatoid Factor

While this test is very important in establishing the diagnosis of RA,

following the levels, does not provide additional useful information

Chemistry Screen

It is appropriate to screen periodically for evidence of renal dysfunction.

Missed Test: Liver Function Tests (LFTs)

Continued assessment of liver function is appropriate for patients taking

methotrexate.
RAPID 3 Assessment

RAPID3 (routine assessment of patient index data 3) is a pooled index of

the 3 patient-reported American College of Rheumatology RA Core Data
Set measures: function, pain, and patient global estimate of status. Each
of the 3 individual measures is scored 0 to 10, for a total of 30. Disease
severity may be classified on the basis of RAPID3 scores: >4 = high; 2.1-
4.0 = moderate; 1.1-2.0= low; and 3 = remission. RAPID3 scores are
correlated with the disease activity score 28 (DAS28) and clinical disease
activity index (CDAI) in clinical trials and clinical care, and are comparable
to these indices in capacity to distinguish active from control treatments in
clinical trials. The RAPID-3 is a patient-driven composite RA disease
activity measure that provides a single score on a continuous scale of 1-
10 based on patient questionnaire. This tool takes about 1.5 minutes of
patient time and <30 seconds of provider time. No laboratory assays are
used. The 2012 ACR guidelines considers the RAPID-3 acceptable for
reliability and responsiveness and to be of good validity.

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Clinical Disease Activity Index (RA CDAI)

The Clinical Disease Activity Index (CDAI) is a patient and provider

composite tool that includes the patient global assessment (PGA),
provider global assessment (PrGA), the 28 swollen joint count, and the 28
tender joint count. It does not require addition of a blood test to check for
an inflammatory marker (such as CRP). Provider-driven tools may be
more time-consuming than patient-based tools, and possible variability
between providers in joint counts must be considered. On the other hand,
the CDAI has been validated as one of the most effective disease activity
rating tools. It can be particularly useful in clinical practice since it can be
calculated in real time; unlike the DAS28, it does not require waiting for
an acute phase reactant test to return from the lab. The 2012 and 2015
ACR guidelines consider it to have good reliability and excellent validity
and responsiveness.

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Erythrocyte Sedimentation Rate (ESR)/C-Reactive Protein (CRP)
Ordering an ESR or CRP is a suitable option for today's visit. ESR and
CRP serve as useful markers of disease activity although in the individual
patient they may not always be helpful for following progression or
improvement of RA that well. The DAS28 is calculated using one of these
two blood tests.

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X-Ray (Hands/Feet)

After initial radiography, there is generally little value in repeating X-rays

regularly to provide evidence for insufficient efficacy of the chosen
treatment. Radiographs cannot demonstrate ongoing inflammation but
can show structural changes. The frequency with which to order
radiographs in RA is debated, but when highly active disease is present
and important therapeutic changes are going to be made then an
assessment of the joint anatomy may be warranted.

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Simplified Disease Activity Index (SDAI)

The Simplified Disease Activity Index (SDAI) is a patient, provider, and

laboratory composite tool that is included in the 6 methods recommended
in the 2012 ACR guidelines for measuring RA disease activity. This assay
consists of 5 items and gives a single score of 0-86 that incorporates
physician joint count, patient global VAS (0-10), provider global VAS (0-
10), 28 tender joint count (0-28), 28 swollen joint count (0-28), and a C-
reactive protein (0-10). The guidelines consider this test to have good
reliability (though retest reliability for the composite has not been
evaluated), excellent validity, and excellent responsiveness. Cut-offs for
the SDAI are as follows: 0-3.3 = remission; >3.3-11.0 = low activity; 11.1-
26.0 = moderate; and >26 is high activity.

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Missing Test: MRI (Hands)

Ordering an MRI is one option for this patient at this visit. It may
demonstrate pathological changes not seen clinically or on x-ray.
However, it only provides data on one or a few joints. This test may have
less impact on most treatment decisions. An MRI may add information not
shown in the plain radiograph, particularly in periarticular tissues and
other soft tissues, detecting bone marrow edema and joint surfaces.
Despite this, ultrasound maybe more preferable.

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Other Orders

Patient Education: Disease prevention

Appropriate management relies on an acceptance of the aggressive

nature of RA and the desirability of halting progression and seeking a
remission. Continued education in regard to this patient's RA and its
treatment is warranted.

Symptom Diary

Patient-driven tools consist of 3 primary components: patient global

assessment (PtGA), a VAS pain score, and quality of life measures
(HAQ, HAQII, or MDHAQ). These tools are relatively quick (< 3 min) and
easy for patients to complete in the waiting room. While these tools are
reliable, valid, and sensitive, they lack formal joint assessment.

Schedule Follow-up Visit: 2 weeks

With this patient's new treatment, ordering a follow-up visit, initially for 2-4
weeks, would be a suitable option. Subsequent follow-up could be done
at greater intervals until finally every 3 months when the patient becomes
stable.

Regular Aerobic Exercise

Gentle exercise can help maintain muscle tone and reduce the risk for a
cardiovascular event. Risks of osteoporosis include unknown calcium and
vitamin D intake, expected ongoing prednisone use, and RA itself (which
can lead to premature osteoporosis). To reduce the risk of fracture,
lifestyle interventions to prevent bone loss should be encouraged,
including increased weight-bearing exercise.

Consults
Physical Therapy

Gentle exercise can help maintain muscle tone and reduce the risk for a
cardiovascular event. Risks of osteoporosis include unknown calcium and
vitamin D intake, expected ongoing prednisone use, and RA itself (which
can lead to premature osteoporosis). To reduce the risk of fracture,
lifestyle interventions to prevent bone loss should be encouraged,
including increased weight-bearing exercise.