A budget impact analysis for making treatment decisions based on anti-cyclic citrullinated peptide (anti-CCP) testing in rheumatoid arthritis

Abstract

Aim: Given that rheumatoid arthritis (RA) patients with high anti-citrullinated protein antibodies (ACPA) titer values respond well to abatacept, the aim of this study was to estimate the annual budget impact of anti-cyclic citrullinated peptide (anti-CCP) testing and treatment selection based on anti-CCP test results.

Materials and methods: Budget impact analysis was conducted for patients with moderate-to-severe RA on biologic or Janus kinase inhibitor (JAKi) treatment from a hypothetical US commercial payer perspective. The following market scenarios were compared: (1) 90% of target patients receive anti-CCP testing and the results of anti-CCP testing do not impact the treatment selection; (2) 100% of target patients receive anti-CCP testing and the results of anti-CCP testing have an impact on treatment selection such that an increased proportion of patients with high titer of ACPA receive abatacept. A hypothetical assumption was made that the use of abatacept would be increased by 2% in Scenario 2 versus 1. Scenario analyses were conducted by varying the target population and rebate rates.

Results: In a hypothetical health plan with one million insured adults, 2,181 patients would be on a biologic or JAKi treatment for moderate-to-severe RA. In Scenario 1, the anti-CCP test cost was $186,155 and annual treatment cost was $101,854,295, totaling to $102,040,450. In Scenario 2, the anti-CCP test cost increased by $20,684 and treatment cost increased by $160,467, totaling an overall budget increase of $181,151. This was equivalent to a per member per month (PMPM) increase of $0.015. The budget impact results were consistently negligible across the scenario analyses.

Limitations: The analysis only considered testing and medication costs. Some parameters used in the analysis, such as the rebate rates, are not generalizable and health plan-specific.

Conclusions: Testing RA patients to learn their ACPA status and increasing use of abatacept among high-titer ACPA patients result in a small increase in the total budget (<2 cents PMPM).

Keywords:

• RA
• ACPA
• abatacept
• adalimumab
• budget impact analysis
• anti-CCP

JEL CLASSIFICATION CODES:

• I10
• I11

Introduction

Biomarkers are objective indications of physiological or pathogenic processes that can be measured and evaluated accurately and reproducibly^1,2. In rheumatology, biomarkers contribute to various clinical objectives such as earlier diagnosis, risk identification to prognosis, disease activity monitoring, assessment of therapy response, and evaluation of drug toxicity^3,4.

Anti-citrullinated protein antibodies (ACPA) are an important diagnostic and prognostic biomarker for rheumatoid arthritis (RA), a chronic heterogenous autoimmune disease^3–5. ACPA are a group of autoantibodies that are directed against citrulline, a nonessential amino acid that triggers immunogenicity. In 2010, the American College of Rheumatology (ACR) and the European League Against Rheumatism (EULAR) included ACPA as part of the serology classification criteria to assist in early RA diagnosis, since ACPA are present before the onset of RA symptoms⁶. Studies have found that patients with ACPA may initially present with similar clinical presentations as patients with no ACPA, but have worse disease course over time, with higher rates of swollen joints, radiological damage, and even mortality^7,8. Due to the worse prognosis associated with the concentration of ACPA, ACPA is associated with higher healthcare resource utilization and thus higher RA-related cost burden⁹. Current guidelines in rheumatologist practice, however, do not incorporate ACPA status in treatment management¹⁰. The rationale for the exclusion of ACPA in treatment selection, specifically for first-line methotrexate, is that some studies have reported that disease activity did not differ between serologic subgroups^11–13.

Recently, however, an increasing number of studies are finding that ACPA is an independent factor for predicting treatment responses to some biologic disease-modifying antirheumatic drugs (bDMARDs), particularly with T-cell activation inhibitor (i.e. abatacept). A post hoc study of data from AMPLE, a randomized control trial of moderate-to-severe RA patients, found that patients with high concentration of ACPA have high response rates to abatacept¹⁴. Specifically, 36.4% of patients in the highest quartile (Q4) of ACPA concentration who received abatacept achieved Clinical Disease Activity Index (CDAI) ≤2.8 after one year of treatment. In the same study, 22.7% of Q4 ACPA patients treated with adalimumab achieved CDAI ≤2.8. After 2 years of treatment, 51.2% of the Q4 ACPA patients on abatacept achieved CDAI ≤ 2.8 and 30.8% of those on adalimumab¹⁴. These results suggest that abatacept may be an effective treatment choice for patients with high ACPA titer. Consistent findings were observed in a recent real-world data study. Harrold et al.¹⁵ used the Corrona RA registry in the United States (US) to compare change in CDAI prior to biologic initiation and 6 months after initiation between patients initiating abatacept and patients initiating a tumor necrosis factor inhibitor (TNFi). While the CDAI response was significantly greater in ACPA positive patients compared to negative patients when treated with abatacept, no difference was observed between ACPA positive and negative groups for TNFi initiatiors. The same study group carried out a follow-up study with an increased number of patients who were also propensity matched on baseline characteristics. The follow-up study found a statistically significantly higher CDAI change with abatacept compared to TNFi among ACPA positive patients who had previously used TNFi¹⁶. The differences in treatment response may be related to the treatments’ different mechanism of actions, with abatacept inhibiting the autoantibody-mediated upregulation of cytokines¹⁷. All of these studies suggest that considering ACPA status could inform appropriate treatment selection, as treatment response varied by ACPA status and the treatment’s mechanism of action.

Given the results of the post hoc AMPLE study analysis, we conducted a budget impact analysis (BIA) to estimate the cost impact of using anti-cyclic citrullinated peptide (anti-CCP) testing to guide treatment selection and increasing abatacept uptake for RA patients with high ACPA titer. This analysis informs payers and decision makers of the budget impact of anti-CCP testing and treatment selection based on anti-CCP test results.

Methods

Model structure

The BIA was structured as a simple cost calculator programmed in Microsoft Excel. The analysis was from a hypothetical US commercial payer perspective with one million insured adults (age ≥18 years) and the target population was patients with moderate-to-severe RA on biologic or Janus kinase inhibitor (JAKi). The two market scenarios compared in this analysis were:

1. Scenario 1: 90% of target patients receive anti-CCP testing and the results of anti-CCP testing do not impact the treatment selection. The current treatment rate of 90% was based on a recent chart review study and an assumption that the test uptake will increase overtime¹⁸.

2. Scenario 2: 100% of target patients receive anti-CCP testing and the results of anti-CCP testing have an impact on treatment selection such that an increased proportion of patients with high titer of ACPA receive abatacept. A hypothetical assumption that the use of abatacept would be increased by 2% in the overall RA population was made.

The total budget in each market scenario was calculated as the sum of anti-CCP test cost and the total treatment cost for the target patient population. The budget impact of increasing anti-CCP testing and the uptake of abatacept for patients with high ACPA titer was calculated by taking the difference in total annual costs between the two market scenarios. In addition to the total budget impact, findings were also reported on a per member per year (PMPY), per member per month (PMPM), per patient per year (PPPY), and per patient per month (PPPM) basis.

Model parameters

Population

The target population for this analysis was adult US patients with moderate-to-severe RA eligible for the initiation or continuation of treatment with biologic or JAKi. An annual RA prevalence rate of 0.5%¹⁹ was applied to the hypothetical 1 million member health plan and estimated that 65.5% of RA patients had moderate-to-severe disease activity²⁰. We estimated 88.4% of patients used disease-modifying anti-rheumatoid drug (DMARD) therapy²¹, of whom 39% received conventional synthetic DMARD (csDMARD) and 61% received non-csDMARD therapy²². We assumed that non-csDMARD patients had already started a biologic or JAKi therapy whereas patients with inadequate response to csDMARD (36.9% of users)²² would switch to non-csDMARDs for the first time. Thus, we estimated 12.7% of moderate-to-severe RA patients were initiating biologics or JAKi and 53.9% were experienced biologic or JAKi users. Figure 1 summarizes the inputs used to estimate the target population.

Figure 1. Derivation of target population. ^aAssuming 0.5% RA prevalence¹⁹. ^bAssuming 65.5% of RA patients have moderate to severe disease activity²⁰. ^cAssuming 88.4% of patients use DMARD therapy²¹, of whom 39% use csDMARD and 61% use non-csDMARD²². 88.4% × 61% = 53.9%; 88.4% × 39% × 36.9% csDMARD non-responder²² = 12.7%. Abbreviations. csDMARD, conventional synthetic disease-modifying antirheumatic drug; DMARD, disease-modifying antirheumatic drug; JAKi, Janus kinase inhibitor; RA, rheumatoid arthritis.

The average weight of a patient was assumed to be 80.4 kg, calculated as the weighted average of US female and male patient weight, with gender distribution sourced from an RA study^19,23.

High ACPA titer

Given the limited understanding on clinical indication of ACPA titers, the threshold of high titer of ACPA is not clearly specified in the practice. Therefore, in this analysis, high ACPA titer was defined as 250 AU/mL or greater, which was the cutoff value of the Q4 ACPA distribution in a chart review study for biomarkers²⁴. Using this definition, 24.9% of the target population would have high ACPA titer and the remainder would be categorized as low ACPA titer²⁴.

Market share

The analysis included both intravenous and subcutaneous forms of abatacept as well as other treatment options including JAKi, TNFi biologics/biosimilars, and other non-TNFi biologics currently available and in use in the US market. Table 1 lists all treatment options considered in the analysis and the overall market shares in both market scenarios. In Scenario 1, market shares represent the current use of biologics or JAKi²⁵ and are assumed to be the same regardless of ACPA status. In Scenario 2, the low ACPA titer group was assumed to have the same market shares as Scenario 1; for the high ACPA titer group, it was assumed that market share increased for abatacept by 2% overall and decreased for all other medications proportionally to their market shares in Scenario 1. The 2% increase in abatacept in Scenario 2 was applied to both intravenous and subcutaneous abatacept products, proportional to their market shares in Scenario 1.

Table 1. Treatment options and market share scenarios.

Drug class	Drug name	Scenario 1^25 (%)	Scenario 2 (%)
T-cell activation	Abatacept IV	7.90	9.23
	Abatacept SC	3.96	4.63
CD-20	Rituximab IV	6.51	6.36
TNFi biologics	Adalimumab SC	25.45	24.87
	Certolizumab pegol SC	3.05	2.98
	Etanercept SC	21.18	20.70
	Golimumab SC	1.47	1.44
	Golimumab IV	4.33	4.23
	Infliximab IV	10.55	10.31
	Infliximab dyyb IV	1.22	1.19
JAKi	Tofacitinib PO	9.09	8.88
	Baricitinib PO	0.17	0.17
IL-6	Sarilumab SC	0.61	0.59
	Tocilizumab IV	2.02	1.97
	Tocilizumab SC	2.20	2.15
IL-1	Anakinra SC	0.31	0.30

Abbreviations. IV, intravenous; IL, interleukin; PO, oral; JAKi, Janus kinase inhibitor; SC, subcutaneous; TNFi, tumor necrosis factor inhibitors.

Anti-CCP testing costs

A one-time cost of $94.83 was applied to all patients receiving anti-CCP testing, consisted of a $14.39 clinical lab fee (CPT: 86200)²⁶ and a $80.44 physician fee (CPT: 99211-99215)²⁷.

Medication costs

Wholesale acquisition costs (WAC) in the year 2019 were used for medication costs²⁸. The prescribing information for each product was referenced to estimate the number of doses needed separately for newly initiating patients and experienced patients over a 1-year course assuming complete adherence to the medication. Medication costs (in 2019 US dollars) and prescribing information for each drug are presented in Table 2. The amount of medication needed was rounded up in the calculation to reflect no vial sharing. Methotrexate and other concomitant drug costs were not considered, since they would be similar across all treatment arms.

Table 2. Medication costs (2019 US Dollars).

Drug name	Dose^a	Dose frequency^a	Strength	Package size	WAC (2019 USD)^28	Total pharmacy cost (2019 USD)^b
Abatacept IV	750 mg	Following initial dose, give at 2 and 4 weeks, then every 4 weeks.	250 mg	each	1,109.03	44,522.06
Abatacept SC	125 mg/1 mL	Once weekly	125 mg/1 mL	Four syringes	4,378.89	56,925.57
Rituximab IV	2 × 1,000 mg	Two 1,000 mg infusions every 24 weeks	10 mg/1 mL	10 mL	939.52	37,580.80
Adalimumab SC	40 mg	Every 2 weeks	40 mg/0.8 mL	Two syringes	5,174.09	67,263.17
Certolizumab pegol SC	400 mg for initial 3 doses, followed by 200 mg thereafter	Every 2 weeks	200 mg/1 mL	each	4,327.43	114,990.73
Etanercept SC	50 mg	Once weekly	50 mg/1 mL	Each	1,293.52	67,263.04
Golimumab SC	50 mg	Once monthly	50 mg/0.5 mL	Each	4,809.02	57,708.24
Golimumab IV	2 mg/kg	Taken at 0 and 4 weeks, then every 8 weeks thereafter	50 mg/4 mL	Each	1,818.51	52,306.46
Infliximab IV	3 mg/kg	Taken at 0, 2, and 6 weeks, then every 8 weeks thereafter	100 mg	Each	1,167.82	25,192.82
Infliximab dyyb IV	3 mg/kg	Taken at 0, 2, and 6 weeks, then every 8 weeks thereafter	100 mg	Each	946.28	20,413.65
Tofacitinib PO	5 mg	Twice daily	5 mg	60s each	4,480.63	54,514.33
Baricitinib PO	2 mg	Once daily	2 mg	30s each	2,136.90	25,998.95
Sarilumab SC	150 or 200 mg	Every 2 weeks	150–200 mg/1.14 ml	2 syringes	3,323.27	43,202.51
Tocilizumab IV	4–8 mg/kg	Every 4 weeks	20 mg/1 ml	4 mL	436.81	28,392.65
Tocilizumab SC	162 mg	Every 2 weeks	162 mg/0.9 ml	Each	984.72	25,602.72
Anakinra SC	100 mg	Once daily	100 mg/0.67 ml	Seven syringes	1,029.47	53,532.44

Abbreviations. IV, intravenous; PO, oral; SC, subcutaneous; USD, US dollar; WAC, wholesale acquisition cost.

^a Dose and dose frequency information from each product’s package insert.

^b The cost presented is before applying any rebates.

In the base case, a 30% discount was applied to WAC cost for adalimumab and etanercept to reflect real-world rebate pricing.

Administration costs

For intravenous medications, administration fees were added. For each initial hour of infusion, there was a cost of $143.08 (HCPCS: 96413) and each additional hour of infusion cost $30.99 (HCPCS: 96415)²⁶. The number of infusions over one year and the number of hours infused at each visit were estimated from the prescribing information. The number of hours infused at each visit was rounded up. Cost of administration or dispensing fee was not considered for subcutaneous or oral products.

Scenario analyses

We conducted scenario analyses on target population and rebates. In the base case, the target population was all patients on biologics or JAKi regardless of their prior exposure to those medications. As a scenario analysis, we evaluated the budget impact for biologic or JAKi-experienced patients only, as well as for naïve patients only. Market shares by previous use of biologic or JAKi status are shown in Supplementary Table S1.

Additionally, we varied the products for receiving rebates. In the base case scenario, 30% rebates were applied to adalimumab and etanercept. In additional scenario analyses, we evaluated scenarios with (1) 30% rebates for all TNF inhibitors and (2) 30% rebates for all TNF and JAKi.

Results

Based on the epidemiological data, in a hypothetical 1 million-member health plan, 3,275 patients were estimated to have moderate-to-severe RA, of whom 2,181 patients would be on a biologic or JAKi treatment.

In the base case with 30% rebates for adalimumab and etanercept, the total estimated budget for the 2,181 patients in Scenario 1 was $102,040,450 (anti-CCP test cost: $186,155; treatment cost: $101,854,295). In Scenario 2, with additional 2% patients receiving abatacept, the anti-CCP test cost budget increased by $20,684; with a higher number of patients on abatacept (n = 63), treatment cost increased by $160,467 totaling an overall budget increase of $181,151. This was equivalent to a PMPM increase of $0.015 (Table 3).

Table 3. Base case results: 30% rebate for adalimumab and etanercept, overall patients (2019 USD).

Outcome	Market share scenario 1	Market Share Scenario 2	Difference
Total budget impact	$102,040,450.00	$102,221,601.00	$181,151.00
Testing cost	$186,154.61	$206,838.45	$20,683.85
Pharmacy + administration cost	$101,854,295.04	$102,014,762.45	$160,467.41
Per member per year (PMPY)	$102.04	$102.22	$0.18
Per member per month (PMPM)	$8.50	$8.52	$0.015
Per patient per year (PPPY)	$46,783.00	$46,866.00	$83.00
Per patient per month (PPPM)	$3,899.00	$3,905.00	$7.00

Abbreviation. USD, United States dollar.

The budget impact results were consistently negligible across the scenario analyses (Table 4). When only biologic or JAKi-naïve patients were considered, the total cost difference was less than $49,000 with a PMPM impact of $0.004. When considering biologic or JAKi-experienced patients only, the PMPM was $0.011.

Table 4. Scenario analyses results (2019 USD).

Outcome	Market share scenario 1	Market share scenario 2	Difference
Scenario analysis: biologic or JAKi-naïve patients only
Total budget impact	$20,330,287.00	$20,379,109.00	$48,822.00
Testing cost	$35,525.90	$39,473.22	$3,947.32
Pharmacy + administration cost	$20,294,761.58	$20,339,636.26	$44,874.68
Per member per year (PMPY)	$20.33	$20.38	$0.05
Per member per month (PMPM)	$1.69	$1.70	$0.004
Per patient per year (PPPY)	$48,841.00	$48,959	$117.00
Per patient per month (PPPM)	$4,070.00	$4,080	$10.00
Scenario analysis: biologic or JAKi-experienced patients only
Total budget impact	$81,579,303.00	$81,714,843.00	$135,540.00
Testing cost	$150,628.71	$167,365.23	$16,736.52
Pharmacy + administration cost	$81,428,674.64	$81,547,477.80	$118,803.16
Per member per year (PMPY)	$81.58	$81.71	$0.14
Per member per month (PMPM)	$6.80	$6.81	$0.011
Per patient per year (PPPY)	$46,223.00	$46,300.00	$77.00
Per patient per month (PPPM)	$3,852.00	$3,858.00	$6.00
Scenario analysis: 30% discount for all TNF inhibitors; overall patients
Total budget impact	$95,811,264.00	$96,133,768.00	$322,504.00
Testing cost	$186,154.61	$206,838.45	$20,683.85
Pharmacy + administration cost	$95,625,109.12	$95,926,929.42	$301,820.30
Per member per year (PMPY)	$95.81	$96.13	$0.32
Per member per month (PMPM)	$7.98	$8.01	$0.027
Per patient per year (PPPY)	$43,927.00	$44,075.00	$148.00
Per patient per month (PPPM)	$3,661.00	$3,673.00	$12.00
Scenario analysis: 30% discount for all TNF and JAKi; overall patients
Total budget impact	$92,539,389.00	$92,936,139.00	$396,750.00
Testing cost	$186,154.61	$206,838.45	$20,683.85
Pharmacy + administration cost	$92,353,234.87	$92,729,300.65	$376,065.78
Per member per year (PMPY)	$92.54	$92.94	$0.40
Per member per month (PMPM)	$7.71	$7.74	$0.033
Per patient per year (PPPY)	$42,427.00	$42,609.00	$182.00
Per patient per month (PPPM)	$3,536.00	$3,551.00	$15.00

Abbreviations. JAKi, Janus kinase inhibitor; TNF, tumor necrosis factor; USD, United States dollar.

With a 30% rebate considered for all TNF inhibitors, the total cost difference was $322,504 with a PMPM difference of $0.027. When the same rebate was applied to all TNF and JAKi, the total budget impact difference increased to $396,750 with a PMPM cost difference of $0.033.

Discussion

There has been an effort to discover biomarkers that can effectively guide and improve treatment selection in RA. Studies have shown the clinical benefits of using abatacept compared to other biologics among patients with high ACPA titer, including higher response rate and treatment retention^{14–16,29–32}. Given such clinical evidence, the goal of this study was to understand the economic impact of increasing the use of anti-CCP testing to guide treatment selection for patients with moderate-to-severe RA on biologics or JAKi and increasing the use of abatacept for those with high ACPA titer. Results from our study showed that the budget impact was a negligible $0.015 PMPM for a hypothetical health plan with one million commercially insured adults in the US. The scenario analyses confirmed the robustness of the results and continued to predict negligible budget impact with varied parameters. Even with higher rebates for other RA agents, the difference in PMPM was consistently less than $0.04. Our results suggest that the budget impact of increasing the use of anti-CCP testing and adding more patients on abatacept will have a minimal budget impact while potentially treating patients more effectively with abatacept.

Several studies have incorporated the clinical benefits of abatacept among ACPA positive patients who had inadequate response to methotrexate to evaluate the cost-effectiveness of abatacept compared to adalimumab. In a cost per responder/remission study, the monthly cost per responder/remission was always lower for ACPA positive patients using abatacept compared to adalimumab regardless of the definition used for responder (i.e. ACR [American College of Rheumatology]20, ACR50, ACR70, ACR90, HAQ-DI [Health Assessment Questionnaire-Disability Index]) or remission (i.e. DAS[disease activity score]28, CDAI, SDAI [Simple Disease Activity Index]) in Germany (−€394 versus −€9,682 per month) and Spain (−€169 versus – €5,422)³³. The same study found similar results for Italy, Canada, and the US, favoring abatacept for ACPA positive patients, except for ACR50 response and DAS28 remission, in which there was a small increase in the monthly cost per responder/remission compared to ACPA positive patients treated with adalimumab (ranging from €5 in Italy to $488 in the US). This study included costs for drugs, concomitant drugs, disease monitoring, and adverse events. Another study developed a decision tree model to compare the cost-effectiveness of abatacept to adalimumab over 2 years in Germany among the same target population as the previous cost per responder/remission study³⁴. The model allowed switching to second-line and third-line of biologic therapy for patients who do not respond to the first line abatacept or adalimumab. The study found that the selection of first-line biologic (i.e. abatacept or adalimumab) impacted the cost per day in remission, with a lower average cost with abatacept compared to adalimumab (€330/day versus €384/day) whereas the choice of second- or third-line biologic had insignificant economic impact. Alemao et al. conducted a cost-effectiveness study comparing abatacept to adalimumab that incorporated HAQ-DI score to calculate quality-adjusted life years (QALYs) from a United Kingdom (UK) payer perspective and stratified the results by ACPA quartile. In all quartiles, the treatment cost with abatacept was higher than adalimumab but QALY was higher with abatacept treatment. The authors concluded that with incremental cost effectiveness ratio of £6,200/QALY for the highest ACPA titer group, abatacept is an effective alternative to adalimumab in patients with high ACPA levels. It is important to note that all these studies referenced the AMPLE trial as the efficacy data source. All studies had different study designs and endpoints but consistently found that abatacept is a cost-effective treatment choice despite the higher drug cost, due to its superior clinical efficacy among ACPA-positive patients.

As a chronic disease, the goal of RA treatment is achieving sustained remission. Due to medical advancement, there are many biological treatment options with different mechanism of actions available today. Given the variety of RA treatments, however, patients are often administered therapies on a trial-and-error basis, with dose escalation, combination therapies, and therapy switch, before finding an optimal treatment therapy³⁵. This can lead to a greater cost of switching medications, lower efficacy of the therapy, extra health care utilization and cost, and potentially lower quality of life for patients^36–39. These negative implications highlight the importance of selecting the optimal treatment early on in the treatment course.

The findings from this study help enhance our understanding of the pharmacy budget impact of increased anti-CCP testing and abatacept use. However, several limitations should be considered when interpreting the results. First, the analysis only considers testing cost and medication costs (i.e. drug cost and intravenous administration fee). Concomitant medications and drug monitoring tests were not considered, which indicate that the total budget in both market scenarios may have been underestimated. However, these costs are typically low and would be similar between the two scenarios; therefore, excluding these costs would not have had a significant impact on the results. Next, some parameters used in the analysis, such as the rebate rates, are not generalizable and health plan-specific. To mitigate this limitation, we conducted scenario analyses around target population and products with rebates, which showed consistent results. In addition, more low-cost biosimilars are being approved in the US for RA, and with higher market shares of biosimilars the results may change⁴⁰. Currently, however, not all approved biosimilars are commercialized in the US and the penetration of biosimilars have been limited. Given their slow uptake, it may take some time for biosimilars to have any meaningful impact on the results of this analysis. Finally, the uptake of abatacept was assumed to increase by 2% in Scenario 2; this was an assumption and varying this value will impact the results.

Conclusion

In conclusion, our analysis shows that testing RA patients to learn their ACPA status and increasing use of abatacept among high-titer ACPA patients results in a small increase in the total budget (<2 cents PMPM). Given that patients with high ACPA titer values respond well to abatacept¹⁴, considering anti-CCP testing for precision medicine and treating ACPA positive patients with abatacept may be a valuable investment.

Transparency

Declaration of funding

The study was funded by Bristol-Myers Squibb (US), Inc.

Declaration of financial/other relationships

XH and FL are employees of Bristol-Myers Squibb (US), Inc. SP, DP, and DK are employees of Pharmerit International, which received consultancy fees from Bristol-Myers Squibb (US), Inc. for this study. FL is a stock shareholder of Bristol-Myers Squibb (US), Inc.

JME peer reviewers on this manuscript have received an honorarium from JME for their review work, but have no other relevant financial relationships to disclose.

Acknowledgements

None reported.