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Medical Policy

Policy Num:      11.001.003
Policy Name:     Anti-CCP Testing for Rheumatiod Arthritis
Policy ID:          [11.001.003]  [Ar / B / M+ / P-]  [2.01.78]

Last Review:      May 26, 2023
Next Review:      Policy Archived
 

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Related Policies: None

Anti-CCP Testing for Rheumatiod Arthritis

Summary

Extensive evidence has established that anti-CCP has a moderately high sensitivity, a high specificity, and is a strong predictor of future erosive arthritis. The test is useful in confirming the diagnosis of RA in patients with early disease, especially when the criteria for a diagnosis of RA are not met by other clinical or laboratory measures. Early identification of patients with RA is important, since early treatment with DMARDs can prevent progression of destructive arthritis and improve functional status. The use of antiCCP for diagnosing RA has been incorporated into the latest diagnostic criteria for RA developed by the American College of Rheumatology (ACR). The evidence suggests that anti-CCP is not useful as a measure of disease activity and/or response to treatment. As a result, the use of anti-CCP is considered medically necessary for the diagnosis of RA and is considered investigational for monitoring disease activity in RA.

Objective

The objective of this review is to evaluate the use of Anti-citrullinated peptide antibodies — Testing in the diagnostic evaluation of patients for RA.

Policy Statements

Measurement of anti-CCP may be considered medically necessary when used as part of the diagnostic workup for rheumatoid arthritis. Measurement of anti-CCP is considered investigational when used to monitor disease activity and/or treatment response.

Policy Guidelines

There is a CPT code specific to anti-CCP testing:

86200: Cyclic citrullinated peptide (CCP), antibody.

According to laboratory information on the internet, Exagen’s Advise MCV which measures IgG antibodies to mutated citrullinated vimentin (MCV) is reported using CPT 83520 – Immunoassay for analyte other than infectious agent antibody or infectious agent antigen, qualitative or semiquantitative; multistep method; not otherwise specified.

Benefit Application

BlueCard/National Account Issues

State or federal mandates (eg, FEP) may dictate that all devices approved by FDA may not be considered investigational. Therefore, FDA-approved devices may only be assessed on the basis of their medical necessity. Review of a claim may not provide information about whether it is being used for diagnosis or to monitor treatment. However, repeated assays would likely represent use to monitor treatment.

Benefits are determined by the group contract, member benefit booklet, and/or individual subscriber certificate in effect at the time services were rendered.  Benefit products or negotiated coverages may have all or some of the services discussed in this medical policy excluded from their coverage.

Background

Anti-CCP assay — In an ELISA assay for ACPA, arginine residues are replaced by citrulline in a mixture of CCP, increasing the sensitivity of the assay for ACPA. These anti-CCP assays have become the principal commercially available assay kits for the detection of ACPA.

The newer-generation assays, including the second-generation anti-CCP antibody assays (anti-CCP2), have improved sensitivity and specificity compared with the original anti-CCP assays [21,26,28,30-32]. The best data regarding test performance characteristics of ACPA come from a 2010 systematic review and meta-analyses of 151 studies [28]. Sensitivity of ACPA was 67 percent and the specificity was 96 percent.

This analysis included the following findings:

●There was substantial heterogeneity in test performance, which resulted from differences in study design, stage of disease, and type of ACPA used in a given study. Cross-sectional and case-control studies of patients with established RA overestimated sensitivity.

●In the cohort studies of patients with RA for less than two years, the sensitivity of anti-CCP2 and RF were nearly the same (58 versus 56 percent), but specificity was significantly higher for anti-CCP2 (96 versus 86 percent).

●There was insufficient evidence to determine whether the combination of anti-CCP2 and RF provides greater benefit than the use of anti-CCP2 alone.

Regulatory Status

N/A

Rationale

Autoantibodies directed against cyclic citrullinated proteins (anti-CCP) has been proposed both as a diagnostic test for rheumatoid arthritis (RA) and as a potential marker of disease activity and/or treatment response. These two potential uses of anti-CCP antibodies will be discussed separately.

Promotion of greater diversity and inclusion in clinical research of historically marginalized groups (e.g., People of Color [African-American, Asian, Black, Latino and Native American]; LGBTQIA (Lesbian, Gay, Bisexual, Transgender, Queer, Intersex, Asexual); Women; and People with Disabilities [Physical and Invisible]) allows policy populations to be more reflective of and findings more applicable to our diverse members. While we also strive to use inclusive language related to these groups in our policies, use of gender-specific nouns (e.g., women, men, sisters, etc.) will continue when reflective of language used in publications describing study populations.

Population Reference No. 1 

Anti-CCP in the Diagnosis of Rheumatoid Arthritis

Current guidelines for the diagnosis of rheumatoid arthritis. The traditional guidelines for diagnosing RA were developed in 1987 and depended on a combination of clinical, laboratory, and radiographic features (see Table 1).(1) This classification system was criticized as suboptimal for use as a diagnostic tool, especially regarding the low sensitivity for patients with early arthritis.(2-4) In 2010, a new set of criteria for diagnosis were developed jointly by the American College of Rheumatology (ACR) and the European League against Rheumatism (EuLAR), which incorporate anti-CCP as a diagnostic criterion for RA(5):

Use of this classification system is intended for patients who have at least 1 joint with clinical evidence of synovitis and for whom the synovitis is not better explained by another disease. For this patient population, a score of 6 or greater is considered to be definitive evidence for RA. (5)

These guidelines are intended to permit diagnosis of RA earlier in the course of the disease. Treatment guidelines for RA support the early initiation of disease-modifying antirheumatic drug (DMARD) therapy to prevent the onset, or slow the progression, of joint damage. (6) The current guidelines assert that early initiation of DMARD therapy leads to better control of disease activity and less joint damage over time. Early treatment with DMARDs can delay, or prevent, joint destruction and disability, thereby improving long-term functional outcomes. Therefore, DMARD therapy should be initiated within 3 months of diagnosis to minimize irreversible joint damage.

Accuracy of anti-CCP in diagnosing RA. The sensitivity and specificity of anti-CCP for the diagnosis of RA has been extensively studied. Several systematic reviews have been published that summarize the available evidence; these are discussed further below. On the most recent update performed in 2012, there continue to be systematic reviews published that summarize the overall diagnostic accuracy of the test.(7) Other research focused on the comparative accuracy of different types of anti-CCP antibodies, such as anti-vimentin.(8-11) The results of these studies may impact the specific type of anti-CCP test performed in clinical care but do not change the overall approach to use of anti-CCP for diagnosing RA.

Whiting et al published a comprehensive systematic review of the diagnostic accuracy of anti-CCP in 2010. (12) A total of 151 studies were identified that contained information on sensitivity and specificity of anti-CCP for diagnosing RA. There was a high degree of heterogeneity for the parameters of sensitivity and specificity across the range of studies included. The pooled sensitivity for all studies was 67% (95% confidence interval [CI], 64% to 70%), and the pooled specificity was 95% (95% CI, 94% to 96%). When confined to cohort studies (n=27), the sensitivity was lower at 60% (95% CI, 54% to 64%), while the specificity was unchanged at 96% (95% CI, 94% to 98%). The sensitivity was higher for secondgeneration anti-CCP tests compared to first-generation tests. Limited data from third-generation testing suggested similar sensitivity for second- and third-generation testing.

Avouac et al published a systematic review (13) that included 68 publications that evaluated the diagnostic accuracy of anti-CCP in patients who met the 1987 ACR criteria for RA and used a control population of either patients with other rheumatologic disorders, or healthy controls. A total of 42 studies evaluated antiCCP2, while the remainder evaluated anti-CCP1, the first-generation version of anti-CCP that is not commercially available. The pooled sensitivity for anti-CCP2 was 68%±15%, and the pooled specificity was 95%±5%. The specificity of anti-CCP2 in healthy controls was greater than 99%, and when the analysis of specificity was confined to patients with other rheumatologic diseases, the specificity ranged from 91% to 99%.

This systematic review included 11 studies that evaluated the predictive ability for anti-CCP in patients with early undifferentiated arthritis. Anti-CCP was not a sensitive marker for RA in these patients with early arthritis, being present initially in only 23% of patients who eventually developed RA. However, the presence of anti-CCP was a powerful predictor of future RA, conferring a 25-fold increased risk of eventually developing RA (95% CI, 18 to 35).

Another systematic review (14) evaluated the accuracy of a subset of anti-CCP antibodies, antimutated citrullinated vimentin (anti-MCV). These auto-antibodies are considered by some experts to have higher sensitivities than that of general anti-CCP autoantibodies. These authors included 16 observational studies in their review. Pooled sensitivity was calculated at 77% (95% CI, 75% to 78%), and pooled specificity was estimated at 89% (95% CI, 87% to 90%). The area under the curve (AUC) on summary receiver operating characteristics analysis was 0.92.

Prospective studies that have assessed the predictive ability of anti-CCP for erosive arthritis confirmed that anti-CCP is a strong independent predictor of future erosive arthritis. In a cohort of 238 patients with the diagnosis of RA followed for a 10-year period, Syversen et al (15) evaluated the predictive ability of anti-CCP, rheumatoid factor (RF), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and other clinical variables. They reported that anti-CCP was the strongest independent predictor of erosive arthritis. Patients with low or moderate anti-CCP levels were 2.6 times (95% CI, 0.9 to 7.2) more likely to exhibit radiographic progression of joint damage, and patients with high levels of anti-CCP were 9.9 times (95% CI, 2.7 to 36.7) more likely to have radiographic progression. Bukhari et al reported data from the Norfolk Arthritis registry, (16) which followed an inception cohort of 427 patients with inflammatory polyarthritis for 5 years. This study also reported that anti-CCP was a strong independent predictor of erosive arthritis (odds ratio, 10.2; 95% CI, 6.2 to 16.9). The authors also concluded that anti-CCP testing was most useful in patients who are RF negative, since 63% of patients who were RF negative and antiCCP positive developed erosive arthritis. In this population, anti-CCP testing may result in an earlier diagnosis of RA, earlier administration of DMARD therapy, and an improvement in long-term functional status.

In another prospective cohort study, Yamane et al (17) assessed the diagnostic utility of anti-CCP in 435 patients seen with arthritic symptoms over a 3-year period, 209 in whom RA was diagnosed. These authors compared numerous permutations of anti-CCP, RF, CRP, and the presence of swollen joints as means of diagnosing RA, using clinician diagnosis as the gold standard. They also examined the variability in diagnostic performance by length of symptoms, with particular emphasis on patients with symptom duration of less than 3 months. The specificity of anti-CCP testing alone was highest in patients with symptoms for less than 3 months (95.4%; 95% CI, 91.4 to 99.3), with a correspondingly high positive predictive value of 87.8%. Therefore, the authors concluded that for this patient population, a positive anti-CCP by itself is sufficient to confirm a diagnosis of RA. The combination of anti-CCP with other clinical and lab markers resulted in a diagnostic algorithm that had a high specificity, ranging from 90.7 to 98.7 and a low sensitivity, ranging from 19.4 to 65.6. None of the tested combinations were clearly superior to the others, nor were they demonstrably superior to the ACR criteria.

Some studies have reported higher sensitivities associated with more recent assays of anti-CCP. These have included third-generation anti-CCP tests, as well as variants of anti-CCP autoantibodies such as mutated citrullinated vimentin (MCV). Wagner et al, (18) as well as other researchers, have reported that measurement of anti-MCV improves the sensitivity of anti-CCP testing. In 193 patients with RA, sensitivity of anti-MCV testing was 71%. Shidara et al (19) reported sensitivities of 88.7% and 89.5% associated with kits for anti-CCP2 and anti-CCP3, respectively. Ryu et al reported a sensitivity of 85% for anti-CCP2 by ELISA. (20) Hwang et al (21) reported accuracy of a commercially available automated chemiluminescent immunoassay. The sensitivity and specificity were 76.8% and 95.3%, respectively, with an AUC of 0.90.

Anti-citrullinated peptide antibodies — Testing for ACPA is useful in the diagnostic evaluation of patients for RA . The sensitivity of ACPA assays for RA varies from about 50 to 75 percent, depending upon the assay and study population, while specificity of ACPA for RA is relatively high, usually over 90 percent . Measurement of ACPA is useful in the differential diagnosis of early polyarthritis because of the relatively high specificity for RA of these antibodies.

Section Summary. A large body of literature has been published on the diagnostic accuracy of anti-CCP antibodies, including several systematic reviews. These studies establish that anti-CCP has a moderately high sensitivity and a high specificity for the diagnosis of RA. The pooled specificity in the systematic reviews ranged from 90% to 95%. This evidence indicates that anti-CCP can confirm diagnosis of RA in patients with signs and symptoms of RA but who do not meet the clinical criteria for diagnosis. A number of different variants of anti-CCP testing have been identified, and the type of anti-CCP antibodies with the optimal clinical performance is being evaluated.

Population Reference No. 2

Anti-CCP for Monitoring Disease Activity in RA

Some experts have proposed that levels of anti-CCP may serve as a marker of disease severity and/or as a measure of treatment response. Several studies have examined whether the presence of anti-CCP correlates with the severity of future joint erosions. Bongi et al (22) reported that the presence of anti-CCP antibodies was associated with a worse prognosis, as defined by the severity of joint erosions. Raza et al (23) reported similar findings and also that the combination of anti-CCP positivity and anti-rheumatoid factor positivity was associated with the greatest severity of erosive bone lesions. However, in patients with anti-CCP antibodies, there is little or no evidence that the absolute levels of anti-CCP are important prognostic indicators of disease activity or severity of joint erosions.

Landmann et al (24) correlated the level of anti-CCP and disease activity using the DAS-28, a measure of disease activity that includes the clinical examination of 28 joints, a patient-reported visual analog scale (VAS) score, and the ESR. Forty patients with RA were followed over a mean of 31 months. There was only a weak correlation found between anti-CCP levels and DAS-28 score (r=0.19, p=0.001), although there was wide variability among individual patients. Other measures, such as clinical symptoms or the ESR, showed a stronger correlation with overall disease activity than did anti-CCP.

Numerous studies have evaluated whether anti-CCP positivity, and the levels of anti-CCP, correlate with treatment response. (25) These studies have generally followed patients with established RA who are being treated with DMARDs, primarily methotrexate and anti-tumor necrosis factor (anti-TNF) agents and have generally found little correlation between treatment, anti-CCP levels, and other measures of disease activity.

In the largest study of this type, Ronnelid et al (26) followed 379 patients with RA under treatment for a total of 5 years. Anti-CCP positivity was reversed in only 3.9% of patients. There was a small but significant decrease in the mean anti-CCP level during the first year of treatment, and this decrease correlated with sulfasalazine treatment but not with other treatment agents. During the subsequent years of follow-up, there was no significant change in anti-CCP levels and no correlation between treatment response, disease activity, and anti-CCP levels.

Dejaco et al (27) evaluated changes in anti-CCP2 and anti-CCP3 in 42 RA patients treated with infliximab, etanercept, or adalimumab. Serum levels of anti-CCP were measured before treatment and following 6 months of treatment. Neither changes in anti-CCP2 nor anti-CCP3 levels were predictive of treatment response with anti-TNF agents. Fisher et al (28) reported that patients with anti-CCP antibodies had a poorer response to infliximab compared to patients without anti-CCP antibodies. Kolarz et al (29) reported that anti-CCP antibody levels in 32 patients with refractory RA who were treated with infliximab did not change significantly over a 6-month period.

Some studies have reported that there is a correlation between anti-CCP levels and treatment response. For example, Klaasen et al (30) prospectively followed 101 patients with RA who were treated with infliximab. Over a period of 16 weeks, there was a correlation between the initial level of anti-CCP antibodies and the degree of treatment response. However, the level of anti-CCP antibodies only explained a small percentage of the variation in treatment response, suggesting that the usefulness in clinical care is limited.
 

The evidence suggests that anti-CCP is not useful as a measure of disease activity and/or response to treatment. As a result, the use of anti-CCP is considered medically necessary for the diagnosis of RA and is considered investigational for monitoring disease activity in RA.

Section Summary. The available evidence on whether anti-CCP antibodies can be used to monitor disease activity or treatment response is insufficient to form conclusions. The majority of studies do not report that there is a significant correlation between anti-CCP levels and disease activity. In those studies that do report such a positive association, the strength of association is probably not strong enough to be useful in clinical care.

Supplemental Information

N/A

Practice Guidelines and Position Statements

Physician Specialty Society and Academic Medical Center Input

In response to requests, input was received from 1 physician specialty society (ACR) and 2 academic medical centers while this policy was under review. While the various physician specialty societies and academic medical centers may collaborate with and make recommendations during this process, through the provision of appropriate reviewers, input received does not represent an endorsement or position statement by the physician specialty societies or academic medical centers, unless otherwise noted. The input while this policy was under review in late 2008 uniformly supported the use of this testing in the diagnosis of rheumatoid arthritis and did not support its use in monitoring disease activity.

Guidelines developed by ACR and the European League Against Rheumatism were published in 2010. (5) These guidelines focused on classification criteria for the diagnosis of RA, especially on early identification of patients who were at risk for persistent/erosive disease. Classification criteria were given in 4 major areas: Joint involvement, serology, acute-phase reactants, and duration of symptoms. AntiCCP was 1 of 2 serologies, the other being RF, that was considered to contribute to the diagnosis of RA. Serologies were classified as negative, low-titer, or high-titer, with different scores associated with each class.

Guidelines were published by the National Collaborating Centre for Chronic Conditions for the management of rheumatoid arthritis in adults under the NICE program in 2003. (31) These guidelines recommend that measurement of anti-CCP should be considered if: (1) there is a clinical suspicion for RA, (2) tests for rheumatoid factor are negative, and (3) there is a need to inform decision-making about starting combination therapy.

Medicare National Coverage

None.

References

1. Arnett FC, Edworthy SM, Bloch DA et al. The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum 1988; 31(3):315-24.
2. Kaarela K, Kauppi MJ, Lehtinen KE. The value of the ACR 1987 criteria in very early rheumatoid arthritis. Scand J Rheumatol 1995; 24(5):279-81.
3. Saraux A, Berthelot JM, Chales G et al. Ability of the American College of Rheumatology 1987 criteria to predict rheumatoid arthritis in patients with early arthritis and classification of these patients two years later. Arthritis Rheum 2001; 44(11):2485-91.
4. Visser H, le Cessie S, Vos K et al. How to diagnose rheumatoid arthritis early: a prediction model for persistent (erosive) arthritis. Arthritis Rheum 2002; 46(2):357-65.
5. Aletaha D, Neogi T, Silman AJ et al. 2010 rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. Ann Rheum Dis 2010; 69(9):1580-8.
6. Guidelines for the management of rheumatoid arthritis: 2002 Update. Arthritis Rheum 2002; 46(2):328- 46.
7. Gao F, Ren L, Zhang CQ et al. Diagnostic value of anti-cyclic citrullinated peptide antibody for rheumatoid arthritis in a Chinese population: a meta-analysis. Rheumatol Int 2011 [Epub ahead of print].
8. Montes A, Perez-Pampin E, Calaza M et al. Association of anti-citrullinated vimentin and anticitrullinated alpha-enolase antibodies with subsets of rheumatoid arthritis patients. Arthritis Rheum 2012 [Epub ahead of print].
9. Nicaise-Roland P, Nogueira L, Demattei C et al. Autoantibodies to citrullinated fibrinogen compared with anti-MCV and anti-CCP2 antibodies in diagnosing rheumatoid arthritis at an early stage: data from the French ESPOIR cohort. Ann Rheum Dis 2012 [Epub ahead of print].
10. Koivula MK, Heliovaara M, Rissanen H et al. Antibodies binding to citrullinated telopeptides of type I and type II collagens and to mutated citrullinated vimentin synergistically predict the development of seropositive rheumatoid arthritis. Ann Rheum Dis 2012 [Epub ahead of print]
11. Svard A, Kastbom A, Soderlin MK et al. A comparison between IgG- and IgA-class antibodies to cyclic citrullinated peptides and to modified citrullinated vimentin in early rheumatoid arthritis and very early arthritis. J Rheumatol 2011; 38(7):1265-72.
12. Whiting PF, Smidt N, Sterne JA et al. Systematic review: accuracy of anti-citrullinated Peptide antibodies for diagnosing rheumatoid arthritis. Ann Intern Med 2010; 152(7):456-64; W155-66.
13. Avouac J, Gossec L, Dougados M. Diagnostic and predictive value of anti-cyclic citrullinated protein antibodies in rheumatoid arthritis: a systematic literature review. Ann Rheum Dis 2006; 65(7):845- 51.
14. Qin X, Deng Y, Xu J et al. Meta-analysis: diagnostic value of serum anti-mutated citrullinated vimentin antibodies in patients with rheumatoid arthritis. Rheumatol Int 2011; 31(6):785-94.
15. Syversen SW, Gaarder PI, Goll GL et al. High anti-cyclic citrullinated peptide levels and an algorithm of four variables predict radiographic progression in patients with rheumatoid arthritis: results from a 10-year longitudinal study. Ann Rheum Dis 2008; 67(2):212-7.
16. Bukhari M, Thomson W, Naseem H et al. The performance of anti-cyclic citrullinated peptide antibodies in predicting the severity of radiologic damage in inflammatory polyarthritis: results from the Norfolk Arthritis Register. Arthritis Rheum 2007; 56(9):2929-35.
17. Yamane T, Hashiramoto A, Tanaka Y et al. Easy and accurate diagnosis of rheumatoid arthritis using anti-cyclic citrullinated peptide 2 antibody, swollen joint count, and C-reactive protein/rheumatoid factor. J Rheumatol 2008; 35(3):414-20.
18. Wagner E, Skoumal M, Bayer PM et al. Antibody against mutated citrullinated vimentin: a new sensitive marker in the diagnosis of rheumatoid arthritis. Rheumatol Int 2009; 29(11):1315-2
19. Shidara K, Inoue E, Tanaka E et al. Comparison of the second and third generation anti-cyclic citrullinated peptide antibody assays in the diagnosis of Japanese patients with rheumatoid arthritis. Rheumatol Int 2011; 31(5):617-22.
20. Ryu HJ, Takeuchi F, Kuwata S et al. The diagnostic utilities of anti-agalactosyl IgG antibodies, anticyclic citrullinated peptide antibodies, and rheumatoid factors in rheumatoid arthritis. Rheumatol Int 2011; 31(3):315-9.
21. Hwang SM, Kim JO, Yoo YM et al. Performance analysis of the ARCHITECT anti-cyclic citrullinated peptide antibody in the diagnosis of rheumatoid arthritis. Clin Chem Lab Med 2010; 48(2):225-30.
22. Bongi SM, Manetti R, Melchiorre D et al. Anti-cyclic citrullinated peptide antibodies are highly associated with severe bone lesions in rheumatoid arthritis anti-CCP and bone damage in RA. Autoimmunity 2004; 37(6-7):495-501.
23. Raza K, Breese M, Nightingale P et al. Predictive value of antibodies to cyclic citrullinated peptide in patients with very early inflammatory arthritis. J Rheumatol 2005; 32(2):231-8.
24. Landmann T, Kehl G, Bergner R. The continuous measurement of anti-CCP-antibodies does not help to evaluate the disease activity in anti-CCP-antibody-positive patients with rheumatoid arthritis. Clin Rheumatol 2010; 29(12):1449-53.
25. Zendman AJ, van Venrooij WJ, Pruijn GJ. Use and significance of anti-CCP autoantibodies in rheumatoid arthritis. Rheumatology (Oxford) 2006; 45(1):20-5.
26. Ronnelid J, Wick MC, Lampa J et al. Longitudinal analysis of citrullinated protein/peptide antibodies (anti-CP) during 5 year follow up in early rheumatoid arthritis: anti-CP status predicts worse disease activity and greater radiological progression. Ann Rheum Dis 2005; 64(12):1744
27. Dejaco C, Duftner C, Klotz W et al. Third generation anti-cyclic citrullinated peptide antibodies do not predict anti-TNF-alpha treatment response in rheumatoid arthritis. Rheumatol Int 2010; 30(4):451- 4.
28. Fisher BA, Plant D, Lundberg K et al. Heterogeneity of anticitrullinated peptide antibodies and response to anti-tumor necrosis factor agents in rheumatoid arthritis. J Rheumatol 2012; 39(5):929-32.
29. Kolarz B, Majdan M, Dryglewska M et al. Antibodies against cyclic citrullinated peptide don't decrease after 6 months of infliximab treatment in refractory rheumatoid arthritis. Rheumatol Int 2011; 31(11):1439-43.
30. Klaasen R, Cantaert T, Wijbrandts CA et al. The value of rheumatoid factor and anti-citrullinated protein antibodies as predictors of response to infliximab in rheumatoid arthritis: an exploratory study. Rheumatology (Oxford) 2011; 50(8):1487-93.
31. National Institute for Health and Clinical Excellence (NICE). National Collaborating Centre for Chronic Conditions. Rheumatoid arthritis: the management of rheumatoid arthritis in adults. 2009. Available at http://publications.nice.org.uk/rheumatoid-arthritis-cg79. Last accessed July 2012.

Codes

Appplicable Modifiers

N/A

Policy History