MEDICAL POLICY

For use with the UnitedHealthcare Laboratory Benefit Management Program, administered by BeaconLBS

RHEUMATOID FACTOR TESTING

Policy Number: CMP - 049
Effective Date: January 1, 2018

Table of Contents Page

BACKGROUND 1
POLICY 3
REFERENCES 5
POLICY HISTORY/REVISION HISTORY 6

INSTRUCTIONS FOR USE

This Medical Policy provides assistance in interpreting UnitedHealthcare benefit plans. When deciding
coverage, the enrollee specific document must be referenced. The terms of an enrollee's document (e.g.,
Certificate of Coverage (COC) or Summary Plan Description (SPD)) may differ greatly. In the event of a
conflict, the enrollee's specific benefit document supersedes this Medical Policy. All reviewers must first
identify enrollee eligibility, any federal or state regulatory requirements and the plan benefit coverage prior
to use of this Medical Policy. Other Policies and Coverage Determination Guidelines may apply.
UnitedHealthcare reserves the right, in its sole discretion, to modify its Policies and Guidelines as necessary.
This Medical Policy is provided for informational purposes. It does not constitute medical advice.

UnitedHealthcare may also use tools developed by third parties, such as the MCG™ Care Guidelines, to assist
us in administering health benefits. The MCG™ Care Guidelines are intended to be used in connection with the
independent professional medical judgment of a qualified health care provider and do not constitute the
practice of medicine or medical advice.

BACKGROUND

Rheumatoid arthritis (RA) is an autoimmune, systemic illness that typically presents in adulthood. The disease is
more common in women than men, and its prevalence in the United States is 0.5-1.0%.1 Tobacco use, family
history, and certain HLA genotypes are associated with increased risk of RA. There is an increased frequency of
HLA-DR1 and HLA-DR4 in Caucasians with RA.2 The hallmark of the disease is synovial inflammation. Subsequent
cartilage and bone erosion ultimately cause significant loss of function. Roughly a quarter of patients cannot
work due to disability within 2 to 3 years of diagnosis.2 In addition to joint manifestations of pain and swelling,
other organs and tissues affected include the lungs, the pleura, and the pericardium. A combination of clinical
and laboratory findings are used to make a diagnosis of RA. Current management is aimed at early identification
of patients with RA, as early diagnosis and treatment have proven to reduce disability.3 With early diagnosis,

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patients can receive treatment with disease-modifying antirheumatic drugs before significant erosive damage
occurs. Rheumatoid factor (RF) is an important diagnostic and prognostic serologic marker for RA.

RF is an antibody against the Fc region of immunoglobulin G (IgG). The antibody can be of the IgM, IgG, or IgA
class. RF was the first autoantibody described in patients with RA. RF is measured by immunoassay.

An early assay used to measure RF was the Rose-Waaler test, an agglutination technique utilizing sheep red
blood cells. The cutoff value for RF positivity depends on the assay used. By enzyme-linked immunosorbent
assay or laser nephelometry, it is >45 IU/mL; by latex fixation it is 1:80. The sensitivity is 70-80%, and the
specificity is 78% (in patients with an established diagnosis).4 Quantitative serum levels of RF may be clinically
useful, though following levels in a patient with an established diagnosis has not been shown to be useful.

Synovial fluid rheumatoid factor can also be assayed. Synovial fluid rheumatoid factor derives from peripheral
blood and synovial plasma cells.

Not all patients with RA are positive for RF. Those who test negative for RF are said to have seronegative
disease. A recent study found the conversion rate for RF in patients with early inflammatory arthritis to be small
(5% over four years).4 In patients with a diagnosis of RA, 50% become positive for RF in the first 6 months, and
85% become positive within the first 2 years.5 Seropositive RA is associated with a more aggressive disease
course characterized by radiographic erosions and a higher incidence of extra-articular disease. RF is not specific
for RA; it can also be elevated in Sjögren syndrome, systemic lupus erythematosus, primary biliary cirrhosis,
postvaccination arthropathy, and infections including bacterial endocarditis, malaria, tuberculosis, osteomyelitis,
and hepatitis C.

There is no gold standard for the diagnosis of RA; subsequently, it can be difficult to diagnose RA with certainty.
The current approach to diagnosis rests on information accumulated from the patient history, physical
examination, radiographic studies, and laboratory tests. A patient’s stated duration of pain and history of
trauma are key clinical points for the differential diagnosis. Joint tenderness on palpation is an important
indicator of synovitis. Serologic tests and acute phase reactants are important for establishing a diagnosis.

New classification guidelines from the American College of Rheumatology were drafted in 2010 to allow for the
earlier diagnosis and treatment of RA.3 The criteria were established to standardize the recruitment of patients
into clinical trials. The criteria are called classification criteria instead of diagnostic criteria due to the
importance of leaving the final diagnostic call in the hands of the physician, independent of the score assigned
to the patient by the classification criteria. The major classification criteria include the number of joints
involved, the serology results (RF and/or anti-citrullinated protein antibody), acute phase reactant results (C-
reactive protein and/or erythrocyte sedimentation rate) and duration of symptoms. In this system, an RF level
>3 times the upper limit of normal for the laboratory and the assay is considered a high-positive RF, and an RF
higher than the upper limit of normal but ≤3 times the upper of limit of normal is considered a low-positive RF.
If a patient has a high-positive RF, 3 points are assigned for the serology category; a low-positive RF is scored 2
points. If the RF result is only reported as positive or negative, the score for a low-positive is assigned. Points
are assigned for all categories. The total score is determined by adding the points from each category. A cutoff
score of ≥ 6 is considered an indicator that a patient is at high risk for developing persistent and/or erosive RA.
While symmetrical involvement of joints was previously considered an important diagnostic criterion, it was
dropped from the new criteria due to a data-driven assessment that concluded it was not an important factor in
predicting which patients would develop an inflammatory arthritis consistent with RA.6

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The clinical picture of RA is variable. Disease onset occurs most commonly at ages 30-50 years, although
juvenile RA and elderly onset RA also exist. Patients can present with pain and stiffness in multiple joints or with
pain in one joint progressing to more diffuse skeletal involvement. The small joints of the hands and feet or the
large joints can be the first involved. Hip involvement is rare.1 Patients usually notice morning stiffness lasting 1
hour or greater along with systemic symptoms including weight loss, anorexia, fever, and fatigue. Joint swelling
and tenderness on palpation are important diagnostic signs. Extra-articular manifestations of RA include
subcutaneous nodules, pulmonary fibrosis, pericardial effusion, and anemia.

Felty’s syndrome is a triad of RA, neutropenia, and splenomegaly with severe joint destruction and frequent
extra-articular manifestations. Over 95% of patients are positive for RF.7

Juvenile RA is classified by the American Rheumatologic Association into categories defined by the signs and
symptoms during the first 6 months of the disease course. These categories are systemic-onset disease,
polyarticular disease, and pauciarticular disease. The polyarticular variant (distinguished by involvement of five
or more joints) is further classified as RF-negative and RF-positive. Children with systemic-onset disease and RF-
positive disease are at highest risk for joint destruction.2

Elderly onset RA is classified into three groups based on symptoms, and treatment differs for the three groups.
One group has symptoms characteristic of polymyalgia rheumatica (a disease of the elderly characterized by
pain and stiffness). Most of these patients have seronegative arthritis and treatment with low-dose
corticosteroids usually suffices. A second group has symmetric joint changes and Sjögren syndrome. The group
with the most severe course has a classic RA presentation. Patients with RF-positive disease have a worse
prognosis.2

The differential diagnosis of RA includes osteoarthritis, fibromyalgia, gout, infectious arthritis, polymyalgia
rheumatic, and connective tissue diseases such as systemic lupus erythematosus. Hepatitis B and C along with
HIV are a few of the infections that cause joint symptomology. Reactive arthritis (formerly known as Reiter’s
syndrome) is a triad of conjunctivitis, urethritis, and arthritis that follows a sexually transmitted disease or an
enteric infection.

According to practice management guidelines from the American College of Rheumatology, patients with
synovitis of at least one joint that is not explained by another disease should be tested for RA.3 The baseline
laboratory tests that are recommended include RF, CBC with differential, erythrocyte sedimentation rate, and C-
reactive protein.2

POLICY

For the following CPT code(s) in Table 1, the patient should have a diagnosis (ICD-10-CM) code(s) listed in the
attached table below.

Table 1. HCPCS Codes (Alphanumeric, CPT AMA)

HCPCS Code Description

86430 Rheumatoid factor; qualitative
86431 Rheumatoid factor; quantitative

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 ICD-10 Diagnosis Codes (Proven)

CMP-049
Rheumatoid Factor ICD10_v2.3

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REFERENCES

1. Rheumatoid arthritis. Centers for Disease Control and Prevention Web site. Available at:
http://www.cdc.gov/arthritis/basics/rheumatoid.htm. Updated July 7, 2017. (Accessed August 10, 2017).

2. Birch JT and Bhattacharya S. Emerging trends in diagnosis and treatment of rheumatoid arthritis.
Primary care, 2010. 37(4): p. 779-792, vii.

3. Aletaha D,Neogi T,Silman AJ, et al. 2010 Rheumatoid arthritis classification criteria: an American College
of Rheumatology/European League Against Rheumatism collaborative initiative. Arthritis Rheum., 2010.
62(9): p. 2569-2581.

4. Barra L,Pope J,Bessette L, et al. Lack of seroconversion of rheumatoid factor and anti-cyclic citrullinated
peptide in patients with early inflammatory arthritis: a systematic literature review. Rheumatology,
2011. 50(2): p. 311-316.

5. Bose N and Calabrese LH. Q: Should I order an anti-CCP antibody test to diagnose rheumatoid arthritis?
Cleve. Clin. J. Med., 2012. 79(4): p. 249-252.

6. Funovits J,Aletaha D,Bykerk V, et al. The 2010 American College of Rheumatology/European League
Against Rheumatism classification criteria for rheumatoid arthritis: methodological report phase I. Ann.
Rheum. Dis., 2010. 69(9): p. 1589-1595.

7. Balint GP and Balint PV. Felty's syndrome. Best Pract Res Clin Rheumatol, 2004. 18(5): p. 631-645.

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POLICY HISTORY/REVISION HISTORY

Date Action/Description
12/07/2017 Annual Policy Review Completed: Updated ICD10 codes as per CMS recommendations.
01/21/2017 Updated ICD10 codes as per CMS recommendations. Removed ICD9 code file.
12/03/2015 Annual Policy Review Completed – changes made:

Added ICD9 diagnosis codes related to arthropathy: 729.5

Added ICD10 diagnosis codes related to arthropathy:

M79.601,M79.602,M79.603,M79.604,M79.605,M79.606,M79.609,M79.621,M79.622,M79.629,
M79.631,M79.632,M79.639,M79.641,M79.642,M79.643,M79.644,M79.645,M79.646,M79.651,
M79.652,M79.659,M79.661,M79.662,M79.669,M79.671,M79.672,M79.673,M79.674,M79.675,
M79.676
10/01/2015 Removed ICD9 table. Embedded ICD9/ ICD10 PDF files.

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