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. 2026 Aug;32(8):955–967. doi: 10.18553/jmcp.2025.25219

RAPID3 disease activity trajectory among patients with rheumatoid arthritis new to specialty pharmacy medications

Alicia L Zagel 1,✉, Dana Simonson 1, R May O’Donnell 1, Ann Harty 1, Tori Grier 1, Ann McNamara 1
PMCID: PMC13404591  PMID: 42329711

Abstract

BACKGROUND:

Understanding disease activity and therapy goals of patients with rheumatoid arthritis (RA) is important to provide patient-centered specialty pharmacy care and achieve positive therapy outcomes. The Routine Assessment of Patient Index Data 3 (RAPID3) is a validated metric to track patient-reported RA disease activity. Consistent and frequent monitoring of RAPID3 scores may provide clinically meaningful insights.

OBJECTIVE:

To describe the trajectory of RAPID3 scores over time and factors related to changes in RAPID3 scores among patients new to specialty medications.

METHODS:

Adult patients with RA who initiated specialty medications were included if they filled medications at least 3 times and had at least 2 RAPID3 scores documented in 6 months. Linear mixed effects regression models estimated trends in RAPID3 scores over time with respect to patient identifiers. Logistic regression models adjusted for baseline RAPID3 severity and estimated adjusted odds ratios (aOR) and associated 95% CIs of achieving a minimal clinically important improvement (≥3.8 points) or low severity/near remission (LS/NR) RAPID3 severity score at 6 months, by patient characteristics.

RESULTS:

Of 312 patients with RA, 195 (63%) had baseline high severity RAPID3 scores. Patients with baseline high severity achieved significant RAPID3 decreases over 6 months (5.9 points; P < 0.0001). Nearly half of patients (N = 147, 47%) had a clinically important improvement and 105 (34%) were LS/NR at follow-up; 67 patients (21%) met both criteria. After adjusting for baseline RAPID3 severity category, medication change (aOR, 0.39; 95% CI, 0.21-0.71) and opting out of full therapy management (aOR, 0.36; 95% CI, 0.19-0.65) were inversely associated with achieving a clinically important improvement. Being LS/NR at follow-up was also inversely associated with medication change (aOR, 0.19; 95% CI, 0.075-0.48) and opting out of full therapy management (aOR, 0.27; 95% CI, 0.12-0.63). Low medication adherence (aOR, 0.28; 95% CI, 0.11-0.72) and Medicaid insurance (aOR, 0.52; 95% CI, 0.29-0.93) were also inversely associated with being LS/NR at follow-up.

CONCLUSIONS:

RAPID3 is a valuable tool in the specialty pharmacy setting, helping assess patient outcomes beyond traditional metrics. Specialty pharmacies should support their patients in striving to reach clinically important improvement and/or achieving LS/NR as measures of quality pharmacy care during the crucial months after therapy initiation and throughout care. Active collaboration between patients and pharmacists is crucial in reaching positive RA disease activity outcomes. To support this, implementing programs that foster patient engagement with pharmacists may be important for optimizing care delivery.

Plain language summary

This study looked at patient-reported disease activity in people with rheumatoid arthritis. People reported their disease activity before and after starting specialty medications. People starting with poorly controlled disease activity had large and helpful changes in disease activity after they started specialty medications. Working closely with the specialty pharmacist and receiving regular medication refills, among other reasons, were related to good disease activity outcomes at 6 months.

Implications for managed care pharmacy

Patients with rheumatoid arthritis who started specialty medications had improved disease activity outcomes when therapy management pharmacists were actively involved in the care team after initiation of specialty medications. Other factors such as not switching medications, payer type, and adherence were also related to positive disease activity outcomes. Promoting patient engagement with specialty pharmacists to assess disease activity and treatment goals, and intervene when goals are not achieved, promotes overall quality and cost-effective health care.

Rheumatoid arthritis (RA) is a chronic, inflammatory autoimmune disease affecting up to 1% of the US population and disproportionately affecting women.1,2 RA usually begins with pain, stiffness, and swelling in peripheral joints such as the fingers and toes; over time, RA may progress in damaging proximal joints, creating cartilage and bone erosion, and leading to joint deformities.3 Although there is no cure, therapy for RA often begins with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) such as methotrexate. Over time, therapy may advance to targeted synthetic DMARDs (tsDMARDs), like tofacitinib or upadacitinib, or biologic DMARDs (bDMARDs), such as adalimumab or etanercept, which are usually dispensed by specialty pharmacies.3–6 The primary goal of DMARD therapy is to stop or slow disease progression by decreasing inflammation, with additional goals of decreasing pain and improving function and overall quality of life.5 In practice, tsDMARD and bDMARD therapy may take up to 3 to 6 months to reveal a patient’s initial response to treatment. However, patient responses can fluctuate over time, necessitating regular assessment of disease activity. Ongoing patient evaluation ensures barriers to care can be identified and therapeutic strategies can be adjusted as needed to achieve optimal patient outcomes.4,6,7

Disease activity caused by RA often precipitates a range of disability including reduced physical and mental health, development of co-occurring chronic diseases, functional and work disability, and premature mortality.3 Monitoring and documenting disease activity at diagnosis and routine follow-up is integral to understanding and managing each patient’s RA therapy. There are 5 standardized and validated assessments of RA disease activity that are favored by the American College of Rheumatology8–10; these assessments facilitate categorization of RA disease activity, which form the foundation of the American College of Rheumatology and the European Alliance of Associations for Rheumatology treat-to-target guidelines, which recommend initially achieving low disease activity then remission.9 The Routine Assessment of Patient Index Data 3 (RAPID3) is one such validated assessment that is commonly used in clinical practice owing to its ease of administration and overall vantage of physical function, pain, and patient global status estimates that can be collected either verbally or via written assessment, and does not require in-person physical or laboratory metrics.11 RAPID3 is subjective and thus may be a good interpretation of a patient’s overall sense of disease activity across time periods, and it correlates well with other validated measures of disease activity, including Disease Activity Score in 28 joints (DAS28) and Clinical Disease Activity Index (CDAI) for RA.12,13

When patients are prescribed specialty medications for RA, therapy management pharmacists engage with patients to dispense the medication, evaluate medication appropriateness, set and assess treatment goals, and provide education on dosing, adherence, side effects, and expected response to therapy.14,15 Specialty pharmacies offer a unique opportunity to measure disease activity over time, providing valuable insight into how medications, patient factors, and interventions influence patient self-reported health outcomes. This study aims to examine the trajectory of RAPID3 scores during the crucial first 6 months of initiating care within the specialty pharmacy. It also seeks to identify factors associated with the improvement of RAPID3 scores between baseline and 6-month follow-up. These insights may help specialty pharmacies identify patients requiring closer monitoring or additional support services, thus enabling more efficient and targeted care for individuals with RA.

Methods

STUDY SETTING

This was a retrospective study of patients with RA who received therapies from a large, full-service specialty pharmacy. This specialty pharmacy treats patients within all 50 United States and is affiliated with a large, Midwestern academic health system. It has in-house therapy management pharmacists who educate, intervene, and work with patients to set and achieve treatment goals, improve quality of life, and mitigate medication therapy problems across several specialty disease states. The specialty pharmacy services approximately 15,000 patients annually. Study data were extracted from the specialty pharmacy therapy management software (Therigy, LLC; Maitland, FL) and medication dispensing system (EnterpriseRx, McKesson Corp.; Irving, TX). The Institutional Review Board at the University of Minnesota determined this study to be exempt from human subjects review.

MANAGEMENT OF RA IN THE SPECIALTY PHARMACY

Initial RA assessments, completed when the patient first receives service from the specialty pharmacy, starts a new medication, or switches to biosimilar medication, serve as a comprehensive evaluation of each patient’s disease history, current symptoms, and baseline RAPID3 score. These assessments also review past and current RA treatments and ensure medication appropriateness. Around the time when the first dose of specialty medication is dispensed, patients are provided with tailored education, pharmacists work with patients to establish personalized goals for specialty care, and staff assess patient preferred method of communication (phone, e-mail, or text messaging system). Through ongoing follow-up assessments, patients are contacted by therapy management pharmacists via telephone to reassess RA disease activity via RAPID3, answer medication questions, discuss side effects, assist with resolving medication issues, monitor adherence, and make referrals to other services as needed. Although the specialty pharmacy attempts to obtain baseline and follow-up assessments on all patients receiving RA specialty medications, patients may choose not to participate in therapy management assessments, including answering RAPID3 questions, at any time.

PATIENT POPULATION

Patients were included in the study if they completed their initial RA assessment in the specialty pharmacy between January 1, 2019, and December 31, 2023, were aged 18 years or older, and filled at least 3 prescriptions within 6 months of initial assessment for a specialty medication including abatacept, adalimumab, anakinra, baricitinib, certolizumab, etanercept, golimumab, sarilumab, secukinumab, tocilizumab, tofacitinib, upadacitinib, and their biosimilars. Included patients also had both a baseline RAPID3 score measured within 30 days of their initial RA assessment and at least 1 follow-up RAPID3 score documented between 3 and 7 months following their initial assessment. To ensure patients were new to the specialty pharmacy, patients were excluded if they had a tsDMARD or bDMARD dispense from this specialty pharmacy documented during the 12 months prior to their initial RA assessment or if their initial RA assessment indicated that they had previously been on specialty RA medications. Patients with a dispense of csDMARD or corticosteroid were included.

VARIABLES OF INTEREST

Disease Activity

Patient disease activity was examined as the primary outcome of interest and measured using the standardized and validated RAPID3 assessment. RAPID3 determines total scores using Likert score assessment of 3 overarching components: function, pain, and global domains, with a total of 10 points available in each domain and 30 points total using an unadjusted scale. Overall, unadjusted RAPID3 scores were classified into severity categories as near remission (0 to 3), low severity (3.1 to 6), moderate severity (6.1 to 12), or high severity (12.1 to 30).11 Equally valid in the clinical setting, weighed RAPID3 scores can be obtained by dividing the cumulative RAPID3 score by 3 and using categories of near remission (0 to 1), low severity (1.3 to 2), moderate severity (2.3 to 4), or high severity (4.3 to 10).

Baseline RAPID3 scores occurred within 30 days of the initial RA assessment, and the score closest to the day of the initial RA assessment was used in analysis. All follow-up scores occurring within 6 months after initial RA assessment were used for longitudinal analyses to assess the trajectory of change in disease activity over time. For analyses centered specifically on outcomes at 6 months, the RAPID3 score documented closest to 6 months following initial RA assessment was considered if it occurred between 3 and 7 months following initial RA assessment, because the specialty pharmacy aims to assess RAPID3 within this time frame. RAPID3 scores of low severity or near remission at 6 months or meeting the minimal clinically important improvement between baseline and 6 months follow-up were goal clinical outcomes. These are consistent with the American College of Rheumatology, which recommends a treat-to-target goal of remission or low disease activity9; a minimal clinically important improvement in RAPID3 score was considered to be a decrease of at least 3.8 points between the baseline RAPID3 measurement and 6-month follow-up RAPID3 score, as per previously published literature.16

Predictors of Interest

Other variables of interest included sociodemographic and treatment-level characteristics. Sociodemographic features were age, gender, primary payer (commercial, Medicare, or Medicaid), and social vulnerability index as per 2023 statewide rankings based on patient zip code, which used census data to rank communities based on household and neighborhood characteristics and ranked communities by their vulnerability to public health, natural, and other disasters on a scale of 0 to 1, where 1 represents the most vulnerable communities.17

Treatment-level factors included specific medications prescribed, wherein biosimilars were grouped with brand-name biologics for analysis; medication therapy problems, as collected by pharmacists within therapy management assessments; medication adherence, as calculated using proportion of days covered (PDC), a measure of medication availability, with adherence achieved as PDC greater than or equal to 80%18; medication switches, as they occurred between specialty medications; and concurrent RA therapies, defined as use of corticosteroids or csDMARDs (methotrexate, hydroxychloroquine, leflunomide, sulfasalazine, or cyclosporine).

Full therapy management occurred when pharmacists and patients collaborated closely at protocol-defined cadences (ie, within month 1, at 3 months, 6 months, and then based on RAPID3 results) to monitor medications, set and track therapy goals, and monitor disease progress. Partial therapy management occurred when patients opted out of 1 or more assessments. Patients could contact pharmacists to receive support when needed. Additionally, treatment management variables such as pharmacist interventions, referrals to the health coach, and therapy goal achievement status were considered. Therapy goals are patient-centered and set collaboratively by the pharmacist and patient based on a patient’s lifestyle and interests (eg, walking a mile without pain, gardening for an hour without pain); follow-up occurs to determine if patients are meeting, progressing toward, or not meeting goals.

STATISTICAL ANALYSIS

Descriptive statistics (ie, frequency and percent, or median and IQR) summarized demographic and treatment characteristics for patients in the sample, compared across baseline RAPID3 severity category using nonparametric tests, specifically chi-square tests for categorical variables and Wilcoxon signed rank tests for continuous variables. Because there were few patients in the baseline low severity and near remission categories, they were combined for analysis. Nonparametric locally weighted scatterplot smoothing (LOESS) regressions estimated the trajectory of all available RAPID3 scores over time based on baseline RAPID3 severity category with smoothness criteria set at 0.15 to evaluate and visualize overall fluctuations in RAPID3 scores over time, and mixed effects linear regression models also provided estimates of RAPID3 scores over time with patient identifiers serving as the random effects to evaluate linear trends in RAPID3 over time while accounting for individual patient variability. Within linear mixed effects regression models, studentized residual plots, specifically, plots of residuals vs predicted values, histograms of residuals, and leverage by residuals, and their associated statistics were examined to determine that model assumptions such as normality, linearity, and homoscedasticity were met.

To understand factors associated with meeting RAPID3 outcomes at 6 months (ie, reaching minimal clinically important improvement between baseline and follow-up RAPID3 score or reaching low severity/near remission), nonparametric tests (ie, chi-square or Fisher exact tests, as appropriate, or Wilcoxon signed rank test) compared demographics and treatment characteristics by outcome group. Variables that were significant at α = 0.10 were then adjusted for baseline RAPID3 severity category to estimate adjusted odds ratios (aORs) and their corresponding 95% CIs of achieving favorable RAPID3 outcomes at 6 months. All analyses were conducted in SAS version 9.4 (Cary, NC).

Results

There were 312 adult patients with RA new to specialty medications who had at least 1 follow-up RAPID3 measured around 6 months following their initial assessment. Of these patients, 195 (62.5%) had a high severity baseline score, 77 (24.7%) scored moderate severity, 20 (6.4%) were low severity, and 20 (6.4%) scored near remission at their initial RAPID3 assessment. Most patients were female (N = 252, 80.8%); many were prescribed adalimumab (N = 197, 63.1%) and used additional RA treatments at baseline (corticosteroids: N = 110, 35.3%; methotrexate: N = 138, 44.2%; other csDMARDs: N = 111; 35.6%). Patients at baseline low severity/near remission were more likely to be male (N = 13, 32.5%) compared with other severity groups (high severity: N = 28, 14.4%; moderate severity: N = 19, 24.7%; P = .011), while high severity baseline patients were more likely to be covered by Medicaid (N = 83, 42.6%) compared with other baseline groups (moderate severity: N = 22, 28.6%; low severity/near remission: N = 11, 27.5%; P = 0.012). Table 1 indicates characteristics of 312 patients by their baseline RAPID3 severity category.

TABLE 1.

Baseline Demographics and Clinical Characteristics of 312 Patients With RA New to Specialty Medications

Total population N = 312 (100.0) Baseline disease severity category P value
High severity N = 195 (62.5) Moderate severity N = 77 (24.7) Low severity/near remission N = 40 (12.8)
Age group, n (%), years 18-34 42 (13.5) 24 (12.3) 8 (10.4) 10 (25.0)
35-49 87 (27.9) 57 (29.2) 25 (32.5) 5 (12.5)
50-64 162 (51.9) 101 (51.8) 40 (52.0) 21 (52.5)
65+ 21 (6.7) 13 (6.7) 4 (5.2) 4 (10.0) 0.14
Gender, n (%) Female 252 (80.8) 167 (85.6) 58 (75.3) 27 (67.5)
Male 60 (19.2) 28 (14.4) 19 (24.7) 13 (32.5) 0.011
Payer type, n (%) Commercial 171 (54.8) 92 (47.2) 52 (67.5) 27 (67.5)
Medicaid 116 (37.2) 83 (42.6) 22 (28.6) 11 (27.5)
Medicare 25 (8.0) 20 (10.3) 3 (3.9) 2 (5.0) 0.012
Social Vulnerability Index, median (IQR) 0.5 (0.2-0.7) 0.5 (0.2-0.7) 0.5 (0.3-0.6) 0.5 (0.2-0.7) 0.50
RA assessments within 6 months, median (IQR) 3 (2-4) 3 (2-4) 3 (3-3) 3 (2-3) 0.36
Baseline RAPID3 domain scores, median (IQR) Function 2.7 (1.3-4.0) 3.7 (2.7-4.7) 1.7 (1.0-2.3) 0.3 (0.0-0.7) <0.0001
Pain 6.0 (4.0-7.0) 7.0 (6.0-8.0) 4.5 (3.5-5.0) 2.0 (0.0-2.0) <0.0001
Global 5.0 (3.5-7.0) 6.0 (5.0-8.0) 4.0 (3.0-5.0) 0.8 (0.0-2.0) <0.0001
First specialty medication dispensed, n (%) Abatacept 16 (5.1) 10 (5.1) 4 (5.2) 2 (5.0)
Adalimumab 197 (63.1) 123 (63.1) 52 (67.5) 22 (55.0)
Etanercept 42 (13.5) 29 (14.9) 7 (9.1) 6 (15.0)
Tofacitinib 17 (5.5) 10 (5.1) 4 (5.2) 3 (7.5)
Other specialty medicationsa 40 (12.8) 23 (11.8) 10 (13.0) 7 (17.5) 0.91
Baseline RA treatment, n (%) Corticosteroids use 110 (35.3) 63 (32.3) 31 (40.3) 16 (40.0) 0.37
Methotrexate use 138 (44.2) 82 (42.1) 38 (49.4) 18 (45.0) 0.55
Other conventional DMARDs 111 (35.6) 74 (38.0) 29 (37.7) 8 (20.0) 0.088
Baseline TM interaction, n (%) Opt in to full TM care 293 (93.9) 181 (92.8) 75 (97.4) 37 (92.5)
Opt out of full TM care 19 (6.1) 14 (7.2) 2 (2.6) 3 (7.5) 0.34
Pharmacist intervention 14 (4.5) 6 (3.1) 6 (7.8) 2 (5.0) 0.24
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a

Other specialty medications included anakinra, baricitinib, certolizumab, golimumab, sarilumab, secukinumab, tocilizumab, and upadacitinib, which were reported in less than 5% of the population in each subcategory.

DMARD = disease-modifying antirheumatic drug; RA = rheumatoid arthritis; RAPID3 = Routine Assessment of Patient Index Data 3; TM = therapy management.

Figure 1 plots LOESS regressions of RAPID3 scores over time by baseline RAPID3 severity category. Patients who scored high disease severity at baseline reached the threshold for moderate severity by 56 days following initial RA assessment. Among patients with baseline high severity, LOESS regressions indicated a change of −37.2% between baseline and 6 months (a 6.3-point decrease), and patients with baseline moderate severity indicated a −18.3% change (−1.8 points). Linear mixed effect models indicated similar improvements, with a 35.9% decrease between baseline and 6 months (a 5.9-point decrease) among patients with baseline high severity (P < 0.0001), and a decrease of 2.5 points (−26.5% change; P < 0.0001) among patients with baseline moderate severity. Baseline low severity/near remission did not indicate statistically significant changes over time (P = 0.85), indicating similar RAPID3 scores throughout 1 year following initial RA assessment. Supplementary Table 1 (468.1KB, pdf) (available in online article) indicates estimates of RAPID3 scores at different time points based on LOESS or linear mixed effects regressions.

FIGURE 1.

Trajectory of RAPID3 Scores Since Starting bDMARDs or tsDMARDs in the Specialty Pharmacy Among Patients With at Least 2 RAPID3 Measurements

FIGURE 1

bDMARD = biologic disease-modifying antirheumatic drug; LOESS = locally weighted scatterplot smoothing; RAPID3 = Routine Assessment of Patient Index Data 3; tsDMARD = targeted synthetic disease-modifying antirheumatic drug.

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When examining RA disease severity outcomes at 6 months, 147 patients (47.1%) had a clinically important improvement of at least 3.8 points at follow-up and 105 (33.7%) achieved low severity/near remission at follow-up; 67 patients (21.5%) met both outcomes and 127 (40.7%) met neither metric (data not shown). The median change in RAPID3 score between baseline and 6 months differed by baseline severity group (baseline high severity: median, −5.00; IQR, −9.33 to −1.50; baseline moderate severity: median, −3.50; IQR, −5.50 to −0.33; baseline low severity/near remission: median, −0.58; IQR, −2.00 to 1.08; P < 0.0001; data not shown). Further, baseline high severity patients were more likely to reach a clinically important improvement of 3.8 points (N = 111, 56.9% vs not reaching clinically important improvement: N = 84, 43.1%; P < 0.0001) but less likely to achieve low severity/near remission at follow-up (N = 157, 80.5% vs achieving low severity/near remission: N = 38, 19.5%; P < 0.0001). Patients who changed medications during the 6-month follow-up were less likely to meet either outcome (reach clinically important difference: N = 21, 33.9%; P = 0.02; achieve low severity/near remission: N = 7, 11.3%; P < 0.0001), as were patients who opted out of full therapy management pharmacist care (reach clinically important difference: N = 21, 32.8%; P = 0.01; achieve low severity/near remission: N = 9, 14.1%; P < 0.0002). Table 2 indicates univariate associations of sociodemographic and clinical characteristics by disease activity outcomes, namely, reaching the clinically important improvement of 3.8 points and achieving low severity/near remission, at 6 months.

TABLE 2.

Examination of Factors Related to RAPID3 Score Trajectory as Measured by a Clinically Important Improvement (≥3.8 Points) or Being Low Severity/Near Remission at 6 Months

Total N = 312 (100.0) Clinically important improvement ≥ 3.8 points P value Low severity/near remission P value
No N = 165 (52.9) Yes N = 147 (47.1) No N = 207 (66.3) Yes N = 105 (33.7)
Baseline RAPID3 severity, n (%) High 195 84 (43.1) 111 (56.9) 157 (80.5) 38 (19.5)
Moderate 77 42 (54.5) 35 (45.5) 43 (55.8) 34 (44.2)
Low/near remission 40 39 (97.5) 1 (2.5) <0.0001 7 (17.5) 33 (82.5) <0.0001
Age group, n (%), years 18-34 42 22 (52.4) 20 (47.6) 27 (64.3) 15 (35.7)
35-49 87 44 (50.6) 43 (49.4) 60 (69.0) 27 (31.0)
50-64 162 89 (54.9) 73 (45.1) 107 (66.0) 55 (34.0)
65+ 21 10 (47.6) 11 (52.4) 0.87 13 (61.9) 8 (38.1) 0.91
Gender, n (%) Female 252 131 (52.0) 121 (48.0) 174 (69.0) 78 (31.0)
Male 60 34 (56.7) 26 (43.3) 0.51 33 (55.0) 27 (45.0) 0.039
Payer, n (%) Commercial 171 84 (49.1) 87 (50.9) 99 (57.9) 72 (42.1)
Medicaid 116 69 (59.5) 47 (40.5) 88 (75.9) 28 (24.1)
Medicare 25 12 (48.0) 13 (52.0) 0.20 20 (80.0) 5 (20.0) 0.022
Corticosteroid use, n (%) Baseline 110 52 (47.3) 58 (52.7) 0.14 71 (65.0) 39 (35.0) 0.62
Follow-up 72 33 (45.8) 39 (54.2) 0.17 50 (69.4) 22 (30.6) 0.53
Methotrexate use, n (%) Baseline 138 77 (55.8) 61 (44.2) 0.36 92 (66.7) 46 (33.3) 0.92
Follow-up 56 32 (57.1) 24 (42.9) 0.48 41 (73.2) 15 (26.8) 0.23
Other DMARD use, n (%) Baseline 111 49 (44.1) 62 (55.9) 0.022 74 (66.7) 37 (33.3) 0.93
Follow-up 46 24 (52.2) 22 (47.8) 0.92 34 (73.9) 12 (26.1) 0.24
Medication change, n (%) 62 41 (66.1) 21 (33.9) 0.020 55 (88.7) 7 (11.3) <0.0001
PDC, median (IQR) 97 (87, 100) 96 (87, 100) 98 (89, 100) 0.16 96 (82, 100) 99 (91, 100) 0.012
Adherent: PDC ≥ 80%, n (%) 260 136 (52.3) 124 (47.7) 0.65 162 (62.3) 98 (37.7) 0.0007
TM care interactions, n (%) Opt in to full TM care 248 122 (49.2) 126 (50.8) 152 (61.3) 96 (38.7)
Opt out of full TM care 64 43 (67.2) 21 (32.8) 0.010 55 (85.9) 9 (14.1) 0.0002
RA goals met 93 38 (40.9) 55 (59.1) 0.0056 35 (37.6) 58 (62.4) <0.0001
Referral to health coach 6 5 (83.3) 1 (16.7) 0.13 6 (100.0) 0 (0.0) 0.10
Side-effect monitoring 32 19 (59.4) 13 (40.6) 0.44 23 (71.9) 9 (28.1) 0.48
Pharmacist intervention 44 26 (59.1) 18 (40.9) 0.37 34 (77.3) 10 (22.7) 0.098
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DMARD = disease-modifying antirheumatic drug; PDC = proportion of days covered; RA = rheumatoid arthritis; RAPID3 = Routine Assessment of Patient Index Data 3; TM = therapy management.

Figure 2 and Figure 3 plot odds ratios, adjusted for baseline RAPID3 severity category, and their associated 95% CIs for achieving a clinically important improvement and reporting low severity/near remission severity at 6 months, respectively, for variables significant at α = 0.10 in univariate analyses, as denoted in Table 2. After adjusting for baseline RAPID3 severity category, patients who met their patient-centered RA goals were 3.51 (95% CI, 1.93-6.37) times more likely to achieve a clinically important improvement in RAPID3 scores and 6.06 (95% CI, 3.36-10.93) times more likely to report low severity/near remission RAPID3 scores at 6 months. Similarly, patients who participated in full therapy management were 2.82 (95% CI, 1.53-6.37) times more likely to meet the clinically important improvement and 3.66 (95% CI, 1.59-8.40) times more likely to reach low severity/near remission at the 6-month follow-up compared with those who participated in partial therapy management. In contrast, those who had a medication change were 2.58 (95% CI, 1.40-4.76) times less likely to meet the clinically important improvement and 5.26 (95% CI, 2.09-13.33) times less likely to achieve low severity/near remission. It is also notable that patients covered by Medicaid (aOR, 1.93; 95% CI, 1.08-3.46) and those who were nonadherent (aOR, 3.51; 95% CI, 11.39-8.85) were less likely to achieve low severity/near remission RAPID3 scores at 6 months.

FIGURE 2.

Odds Ratios, Adjusted for Baseline RAPID3 Severity Category, and Corresponding 95% CIs for Variables Associated With Reaching a Minimal Clinically Important Improvement (≥3.8 Points) in RAPID3 Scores by 6 Months

FIGURE 2

DMARD = disease-modifying antirheumatic drug; RA = rheumatoid arthritis; RAPID3 = Routine Assessment of Patient Index Data 3; TM = therapy management.

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FIGURE 3.

Odds Ratios, Adjusted for Baseline RAPID3 Severity Category, and Corresponding 95% CIs for Variables Associated With Reaching Low Severity/Near Remission by 6 Months

FIGURE 3

RA = rheumatoid arthritis; RAPID3 = Routine Assessment of Patient Index Data 3; TM = therapy management.

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Discussion

Specialty pharmacies play an integral role in evaluating disease activity and its impact on quality of life in patients with RA, while also facilitating personalized interventions that support individuals in achieving treatment goals.14,19 As such, evaluating RAPID3 trajectories within individuals or across populations, especially when considering the factors affecting disease activity, can offer valuable insight into delivering effective and efficient pharmacy services.14,20,21 The current analysis indicates that baseline RA disease activity scores affect the overall trajectory of RA disease activity scores. Patients entering the specialty pharmacy with baseline high severity RAPID3 scores achieve statistically significant and clinically important changes over a 6-month period, decreasing an average of approximately 6 points, whereas patients beginning with moderate severity decreased an average of approximately 2 points in that time. In contrast, those starting with low severity/near remission RAPID3 scores had limited potential for further decreases and tended to maintain stable disease activity over time, which is ideal from a clinical standpoint. Further, this study identified key factors that are adversely associated with 6-month disease activity outcomes, including medication changes, using partial instead of full therapy management care, poor adherence, and Medicaid insurance. This insight offers strategic guidance to establish meaningful patient goals, tailor assessment frequency and content, and uncover nonresponders and obstacles that hinder optimal outcomes, thus ultimately advancing the quality and effectiveness of specialty pharmacy care services.

Patient clinical characteristics were similar at baseline across RAPID3 disease severity categories; however, the trajectory of their RAPID3 scores varied significantly and meaningfully over 1 year. Patients beginning with high disease activity severity indicated significant improvements over time but were not as likely to achieve low severity/near remission. This indicates the strength of using the minimal clinically important improvement as a short-term goal for some patients entering the specialty pharmacy.16 Although reaching low severity may be the ultimate goal of specialty medication therapies,9 and has been shown to be associated with decreases in significant costs of care,22,23 additional knowledge such as patient comorbidities, lifestyle factors, and health care utilization may help patients and pharmacists gauge their expected disease activity trajectories accordingly, although these were not assessed in the current analysis. Considering both the minimal clinically important improvement and reaching near remission or low severity disease state as reporting metrics may aid specialty pharmacies in enhancing patient-centered care and more appropriately gauging the benefits they provide to their patient population.24 However, larger studies should further evaluate if there are subpopulations wherein one outcome is superior to better guide the use of these outcome metrics in the specialty pharmacy.

The American College of Rheumatology recommends treatment decisions be reevaluated within at least 3 months, based on treatment efficacy.9 It is noteworthy that despite the fact that 41% of patients failed to achieve a clinically significant improvement or reach low disease activity/near remission RAPID3 scores, only 20% underwent a medication change within the first 6 months of treatment. Among patients who failed to meet positive RAPID3 outcomes, treatment may have been optimized by increasing the dose, which may eventually lead to positive RAPID3 outcomes when a longer time frame is examined; in other situations, treatment adjustments may be delayed (eg, physician access or payer requirements) or overlooked for a variety of reasons. Specialty pharmacists are uniquely positioned to provide ongoing efficacy assessments and timely interventions during this critical phase of the patient journey. As such, the added support of full therapy management care to help mitigate medication adverse effects within the specialty pharmacy is an invaluable resource21 and notably associated with greater odds of achieving positive disease activity outcomes at 6 months in the current study compared with those who opted out of full therapy management; however, it should be noted that therapy management pharmacists follow patients to collaborate to achieve positive outcomes and reach treatment goals for the entire duration of their treatment within the specialty pharmacy. Therapy management pharmacists help patients navigate all avenues of the medication process starting prior to medication initiation to expedite medication access; they can provide treatment monitoring, provide side-effect management and mitigation, make recommendations to prescribers regarding dosing or concomitant medication use, educate patients on their medications and disease status, provide continuity-of-care services, and create personalized patient experiences within the specialty pharmacy.14,15 Therapy management pharmacists in our specialty pharmacy also use data-driven methodologies to enhance patient care; in addition to using RAPID3 assessments to evaluate whether patients with RA are achieving their personalized health goals, they also use them to determine the effectiveness of medication therapy. There may be valid reasons for persistently high or rising RAPID3 scores, such as long-standing disease, comorbidities, recent injuries, or surgical recovery.25,26 However, when treatment goals remain unmet without a clear clinical justification, our pharmacists proactively engage patients and collaborate with their prescribers. This approach aims to help prevent prolonged use of costly and ineffective therapies and supports efforts to achieve lower disease activity.9

Medication adherence is crucial to achieving favorable RA disease outcomes. This study noted exceptionally high specialty medication adherence (PDC median, 0.97; IQR, 0.87-1.00) and further indicated that adherence was associated with greater odds of reaching low severity/near remission disease activity at 6 months following the beginning of specialty pharmacy care. Previous studies indicate rates of nonadherence among patients with RA as high as 30% to 80%27 and similarly note its association with higher disease activity, for example, greater DAS28 scores and tender joint counts.28 The current study’s use of PDC may result in higher estimates of adherence because of its measurement of medication availability; however, literature has indicated that care within health system–owned specialty pharmacies is associated with high levels of adherence within RA and that high adherence is associated with lower out-of-pocket medication costs and health care utilization.29,30 Interventions to achieve high medication adherence within RA, thereby improving outcomes, are not widely published, but tailored approaches that identify nonadherent patients for intensive education and counsel have been proposed,27,31 and implementing therapy management programs has been found to be helpful.32 Further, the promotion of in-depth knowledge of inflammatory conditions and associated medications by health care team members, along with providing long-term patient education and collaboration, may increase adherence rates.33 These methodologies are standard in our specialty pharmacy wherein the specialty pharmacy gains medical insight from rheumatologists, while specialty pharmacists advance understanding of medication therapies within the health system and beyond. Although our specialty pharmacy cares for patients within and outside of our health system, the medical insight and patient care journey provided by rheumatologists assists in providing similar comprehensive and patient-centered care across our population.

Interestingly, almost 13% of patients in the sample presented with baseline low severity/near remission RAPID3 scores, despite being indicated as new to specialty medications. This highlights the importance of understanding each patient’s clinical history and the limitations and strengths of the RAPID3 assessment tool, which creates the critical context for pharmacists in setting treatment goals.9,21 In most cases, the American College of Rheumatology recommends that DMARD-naive patients begin with conventional DMARDs like methotrexate before considering specialty medications.9 Whereas some patients may respond well to csDMARDs, others may be unable to tolerate them because of side effects or contraindications.6 Additionally, temporary improvements in RAPID3 scores can sometimes result from short-term oral corticosteroid use34,35; these medications are commonly used as patients begin specialty medications until the efficacy of the new medication is revealed.9 It should also be highlighted that the current study found patients with Medicaid insurance to have worsened presentations of disease activity at baseline than patients with commercial insurance, which is consistent with previous literature that posits that lack of access to specialists and greater counts of comorbidities as potential contributors among those with Medicaid.36 It is important to understand that RAPID3 has limitations and should be considered accordingly. As a patient-reported tool, it does not include physician assessment of signs and symptoms (eg, rheumatoid nodules, heart, or lung involvement), radiographic evidence of joint damage, or laboratory assessments and may underestimate disease activity in individuals with elevated inflammatory markers who remain at risk for joint damage despite the low RAPID3 scores.37,38 Published studies report moderate to strong correlation with other indices, with coefficients of 0.66 for DAS28 and 0.70 for CDAI.37 However, studies indicate that 21% of those with low severity/near remission RAPID3 scores measure as moderate or high using DAS28 and 19% using CDAI.13,37,39 This suggests that some patients with favorable RAPID3 scores may still experience significant disease activity or inflammation; although RAPID3 is a useful tool within the specialty pharmacy to ensure patients do not remain on specialty medications if deemed ineffective, other validated assessments employed by rheumatologists may be a more comprehensive overview of disease activity.

LIMITATIONS

This was a retrospective study using data collected during routine patient care; thus, data accuracy is limited by patient-reported experience, pharmacist interactions, and staff data entry. For example, it is possible that patients were included in analysis when they had been previously treated at other specialty pharmacies. To address this, patients were excluded if they had an RA medication dispense documented during the 12 months prior to their initial RA assessment or if their initial RA assessment indicated previous use of specialty medications. Similarly, patient comorbidities may be related to RA disease trajectories and outcomes; data regarding comorbidities were limited such that they could not be employed within analyses. Future studies may wish to examine the role of comorbidities in RAPID3 trajectories over time. Further, because of the nature of the specialty pharmacy’s therapy management platform, it is highly likely that pharmacist interventions are underestimated because pharmacists often use notes fields instead of categorical fields when caring for patients. Similarly, owing to constraints in data availability, patient comorbidities were not assessed for their association with RAPID3 metrics. It should also be noted that because RAPID3 is patient reported, it may be sensitive to other environmental factors occurring in a patient’s life,40,41 despite that it asks specifically for patients to respond in the context of their disease state. For example, it is difficult for the patient to differentiate pain that originates from RA vs a previous injury or surgery, excess physical activity, or comorbid condition such as osteoarthritis or fibromyalgia. Lastly, although not discussed in detail, payer type may serve as a proxy for broad social and structural factors,42–44 and thus, further research is pertinent to determine how specific factors are associated with RA disease activity trajectories.

Conclusions

Following the trajectory of patient-reported disease activity via RAPID3 assessments is beneficial within the specialty pharmacy and for patients, payers, and prescribers, as it captures a patient’s subjective view of their physical function, pain, and patient global assessment. This study indicated that disease activity trajectories are dependent on perceived disease severity at baseline, with more significant improvements made by patients with high severity RAPID3 scores beginning specialty pharmacy care and continued stable reports by patients starting at lower severity. By 6 months, positive disease activity outcomes were associated with choosing to receive full therapy management care, remaining adherent to medications, remaining on the same medication, and having a commercial payer. These understandings may aid specialty pharmacies in prompting their patients to engage with the specialty pharmacy to discover medication-related issues, set realistic treatment goals, and have advocates who are experienced in complex specialty medications.

Disclosures

The authors report no disclosures.

Acknowledgments

The authors acknowledge the contributions of Susan Chhen, PharmD, for her review of the study protocol, and Eric Betzold, MS, for developing the initial SQL code to pull data from the health record.

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