Integrated health system pharmacy role in adherence, persistence, and adverse effect management for oral chronic lymphocytic leukemia therapy

Abstract

BACKGROUND:

Oral oncolytic therapy for the management of chronic lymphocytic leukemia (CLL) or small lymphocytic leukemia (SLL), such as ibrutinib, acalabrutinib, and venetoclax, have vastly changed CLL treatment. Although effective, adverse effects of these agents remain challenging. Pharmacists have an important role in managing oral chemotherapy, educating patients, and intervening to reduce adverse effects.

OBJECTIVE:

To evaluate medication utilization patterns (adherence, persistence, discontinuation, and switching therapy) and pharmacists’ management of adverse effects in patients initiated on an oral oncolytic therapy for CLL/SLL at an integrated health system specialty pharmacy.

METHODS:

This single-center, retrospective review of data collected from electronic health records and a specialty pharmacy management system was conducted at the institution’s outpatient oncology and hematology clinics from January 1, 2019, through June 30, 2022. Patients were included if they were prescribed acalabrutinib, ibrutinib, or venetoclax for treatment of CLL/SLL. Patients were followed through December 2022, with all patients having at least 6 months of follow-up. Primary outcomes were adherence (calculated as proportion of days covered [PDC] for patients with ≥3 fills), persistence (defined as absence of a ≥30-day gap in treatment), discontinuation or therapy switch, and reasons for discontinuation or therapy switch. A secondary analysis evaluated pharmacist interventions and intervention outcomes for patient-reported adverse effects. Descriptive statistics were used for analyses.

RESULTS:

There were 145 patients included in the study; among the 137 with at least 3 fills, the median PDC was 0.98 (interquartile range [IQR] 0.90-1.00) and 51 patients (37%) were found to be nonpersistent with median time to nonpersistence of 10 (IQR 6-19) months. Among 53 patients (39%) who discontinued therapy, common reasons included adverse effects (n = 26, 49%) and disease progression (n = 25, 47%). Common reasons for switching therapy among patients with a switch (n = 25; 17%) included adverse effects (n = 18, 72%) and progressive disease (n = 8, 32%). Pharmacists completed 141 interventions in 69 patients (43%) and most often acted by reviewing or updating the patient’s chart (n = 85, 60%) and counseling patients (n = 50, 35%). Intervention outcomes included identified issue resolved (n = 79, 56%), follow-up care scheduled (n = 9, 6%), medication administration held (n = 2, 1%), dose adjustment made (n = 4, 3%), or medication discontinued (n = 4, 3%).

CONCLUSIONS:

In a population of patients initiating oral CLL/SLL therapy through an integrated health system specialty pharmacy, adherence and persistence to therapy was high. Adverse effects were attributed in 36% of therapy discontinuations and 72% of therapy switches, indicating a continued opportunity for specialty pharmacists to help manage and mitigate adverse effects. Pharmacist interventions were common and sometimes resulted in therapy changes.

Plain language summary

Pharmacists play an important role in helping patients who take medicine for chronic lymphocytic leukemia (CLL), a type of cancer. Pharmacists can make sure patients are taking their medicine correctly. They also help with side effects of the drugs.

Implications for managed care pharmacy

This study found a high adherence rate in patients with CLL receiving oral therapy despite patients commonly reporting adverse effects. However, discontinuations and nonpersistence that occurred were often a result of reported adverse effects. Managed care pharmacy stakeholders should acknowledge the need for a high level of monitoring for patients receiving oral therapy for CLL/small lymphocytic leukemia, such as that provided in an integrated health system specialty pharmacy, to achieve benefits of treatment.

Chronic lymphocytic leukemia (CLL) and small lymphocytic leukemia (SLL) are hematologic malignancies characterized by an accumulation of leukemic cells, partially mature or immature lymphocytes, found in blood, bone marrow, and lymphoid tissues. In CLL, most leukemic cells can be found circulating in blood, whereas in SLL the majority are found in lymph nodes. ¹ CLL and SLL are considered the same disease state and therefore treated similarly. ² Previously, chemoimmunotherapy was considered standard of care as frontline therapy; however, the addition of novel targeted oral oncolytic therapy has shifted the treatment landscape. These oral agents, such as acalabrutinib, ibrutinib, and venetoclax, are now routinely used and recommended as first-line therapy. ¹ Acalabrutinib and ibrutinib are Bruton tyrosine kinase inhibitors (BTKis); venetoclax is a B-cell lymphoma-2 inhibitor. ^{3 – 5}

Though oral oncolytic therapy presents a more convenient option for patients by not requiring an infusion, these medications have several documented adverse effects that require close monitoring. Hematologic abnormalities (neutropenia, thrombocytopenia, anemia), fatigue, nausea, diarrhea, musculoskeletal pain, and upper respiratory infections have been observed among all 3 agents (acalabrutinib, ibrutinib, and venetoclax) in high percentages of patients. ^{3 – 5} Bruising and rash are unique to the BTKi class and reported in more than 20% of patients. Additionally, headache with acalabrutinib, pyrexia with ibrutinib, and cough and swelling with venetoclax, are seen in at least 20% of patients. ^{4 , 5} Each of these oral therapies have shown excellent antitumor activity in clinical studies, but there is limited adverse effect literature demonstrating how these agents are tolerated in the real-world setting. More studies evaluating the adverse effects and interventions to address them are needed to better understand the impact of adverse effects on medication utilization patterns. Providing real-world examples in an integrated health system specialty pharmacy (IHSSP) of how pharmacists can intervene to help mitigate adverse effects can help inform best practices and care for patients with CLL/SLL. The adverse effect profile of oral CLL/SLL agents necessitates a thoughtful and comprehensive treatment-monitoring approach to help patients mitigate adverse effects.

Vanderbilt Specialty Pharmacy is an IHSSP in which pharmacists are embedded in specialized clinics as part of an interdisciplinary team comprising physicians, nurses, physician assistants, and pharmacists. Several studies have shown using a specialty pharmacy may lead to increased adherence, even more so with health system specialty pharmacies. ⁶ Studies comparing oral oncolytic adherence for patients filling medications at an IHSSP with patients filling at an external specialty pharmacy found increased adherence rates among patients using an IHSSP. ^{7 , 8} IHSSP pharmacists help patients initiating oral oncolytic therapy navigate medication access requirements, provide initial and ongoing education, and monitor medication safety and patient response. Implementing a specialty pharmacist in the health system setting has also demonstrated increased patient and provider satisfaction, as well as cost savings for patients. ^{9 , 10}

Literature suggests that IHSSPs can improve patient monitoring and adherence to oral oncolytic treatment. Studies have shown improved adherence in treatment of solid tumor malignancies and hematologic malignancies when patients use an IHSSP for dispensing oral oncolytic therapy. Academia et al found the median adherence, measured by proportion of days covered (PDC), to be 0.99 when patients filled an oral oncolytic therapy through an IHSSP compared with 0.91 when filling through an external specialty pharmacy. ⁸ Mulunek et al investigated patients with chronic myeloid leukemia who were managed by a pharmacist-led oral chemotherapy management program. They found an increase in adherence and interventions that led to better patient outcomes than published clinical trial data. ⁹ However, it is unknown if the positive outcomes in an IHSSP model seen in these studies translate to patients taking specialty medications for CLL/ SLL. Understanding medication utilization patterns in the IHSSP setting can help pharmacists and providers improve patient care and outcomes in patients with CLL/SLL. Therefore, the objective of this study was to evaluate medication utilization patterns, including adherence, persistence, discontinuation, and switching of therapy in patients receiving oral oncolytic therapy for CLL/SLL at an IHSSP. Additionally, the study aimed to describe pharmacist intervention actions and outcomes for patients experiencing adverse effects on oral oncolytic therapy.

Methods

STUDY DESIGN

A single-center, retrospective, observational study was conducted. Data were collected from January 2019 through June 2022. Patients were followed through December 2022, with all patients having at least 6 months of follow-up. This study was approved through the institution’s Institutional Review Board (#221877).

SETTING

This study was conducted at an IHSSP at Vanderbilt University Medical Center wherein specialty pharmacists are embedded in the outpatient clinics as part of the interdisciplinary team. Between the oncology and hematology outpatient clinics, 3 full-time and 2 part-time specialty pharmacists are responsible for managing medication access, educating and monitoring patients, and optimizing treatment for patients receiving oral oncolytic therapy. Patients filling medication through the IHSSP are evaluated monthly for adherence, adverse effects, medication changes, and health care utilization. Patients are also assessed by the pharmacist annually to ensure appropriate safety and therapeutic monitoring is completed as part of the clinic-specific monitoring protocol. Pharmacists intervene as needed if a patient reports an issue during follow-up monitoring or separately by contacting the clinic or the pharmacy.

PATIENT SELECTION

Patients prescribed acalabrutinib, ibrutinib, or venetoclax by one of the institution’s oncology providers for the treatment of CLL/SLL were included. Patients with at least 1 fill during the study period at the IHSSP were included provided they continued with the clinic for at least 6 months of follow-up. Patients were followed until the conclusion of the study to determine any discontinuations or therapy switches. Patients were excluded if they were lost to follow-up, received a stem cell transplant, transferred care outside of the Vanderbilt Health system, or if the medication was not prescribed for a US Food and Drug Administration–approved use.

DATA COLLECTION

Data were collected through electronic health records (EHRs), a specialty pharmacy management system, and pharmacy dispensing software by either data extraction or manual chart review. A data collection protocol was used for consistency between 2 pharmacist investigators manually collecting data. Data were entered into REDCap (Research Electronic Data Capture) hosted at Vanderbilt University for analysis. REDCap is a Health Insurance Portability and Accountability Act–secure, web-based software platform designed to support data capture for research studies. ^{11 , 12}

OUTCOMES MEASURES

Primary outcomes were adherence (calculated as PDC), persistence (defined as absence of a ≥30-day gap in treatment), discontinuation of therapy (medication stopped and not restarted at any point during the study period or follow-up), and switching of therapy (stopping initial treatment and initiating either another oral agent or an oral agent in combination with an infusion). PDC was calculated as the number of days with medication available between the date of the first fill and the last fill within the study period. If the medication was refilled before the previous fill was exhausted, excess supply was carried forward. Excess supply was truncated at the date of the last fill. A 30-day gap was chosen as a permissible gap for persistence, as pharmacists felt any logistical issues that would cause a gap would be less than 30 days and patients were unlikely to hold therapy for a clinically appropriate reason for more than 30 days. The date of nonpersistence was defined as 30 days after the medication had been exhausted. Follow-up time for patients without a 30-day gap in therapy was either the date of discontinuation (patient was no longer eligible for the persistence calculation) or the end of the study period. Because pharmacy claims are an indirect measurement of adherence, for this study a minimum of 3 fills were required for adherence and persistence calculations to ensure that patients were established on therapy and to appropriately evaluate medication-taking behavior. ¹³ Adherence and persistence were calculated at the therapy level, meaning if a patient switched medications, excess supply of the first medication would be removed at the date of the initial fill of the second medication.

Secondary outcomes were rate and reasons for medication discontinuation or switching and number and outcomes of pharmacist interventions due to adverse effects. Patients who discontinued were removed from the persistence calculation after the date of discontinuation, which was confirmed by EHR review. Therefore, discontinuations were not considered nonpersistence. Adverse effects were identified during monthly refill monitoring calls, patient-requested pharmacist follow-up calls, office visit documentation, or if the patient contacted the clinic or pharmacy. Adverse effects were reported as any negative reactions that resulted after a study drug was initiated.

Pharmacists’ interventions were defined as an action taken by the pharmacist to address an issue and were documented during normal routine care. Each intervention was documented with an intervention type (reason for the intervention), action taken, and outcome. Action taken denotes what the pharmacist did to resolve the issue. The outcome of the intervention indicates what resulted from the pharmacist intervention. The intervention is considered resolved if no further action is required. Each intervention may have 1 or more outcomes, and results were presented at the patient-level; therefore, in some instances (such as reasons for discontinuation), totals may exceed 100%.

DATA ANALYSIS

Data were analyzed using descriptive statistics. Continuous variables were presented as medians and interquartile ranges (IQRs), whereas categorical variables were summarized as frequencies and percentages. The Kaplan-Meier method was used to display the probability of remaining persistent.

Results

A total of 157 patients were identified for inclusion (Supplementary Figure 1 ^{(234.4KB, pdf)} , available in online article). Twelve patients were excluded because of off-label indication (n = 2), loss to follow-up (n = 1), stem cell transplantation (n = 4), and transfer of care outside of Vanderbilt University Medical Center (n = 5). Of the 145 patients included (Table 1), most were White (n = 130, 90%) men (n = 96, 66%) with a median age of 69 (IQR 60-76) years. The most common oral oncolytic prescribed was ibrutinib (n = 77, 53%). At baseline, the most common documented comorbid conditions were hypertension (n = 74, 51%) and gastroesophageal reflux disease (n = 45, 31%). More than half of the patients had genetic testing documented in their medical record (n = 99, 68%).

TABLE 1.

Patient Demographics (N = 145)

Characteristic	n (%)
Age (at start of medication use), median [IQR]	69 [60-76]
Legal sex
Male	96 (66)
Female	49 (34)
Race
White	130 (90)
Black	7 (5)
Duration of disease in years (at start of medication use), median [IQR]	6 [2-10]
Prescription insurance
Medicare	74 (51)
Commercial	58 (40)
Tricare	11 (8)
Other	2 (1)
CLL/SLL treatment
Ibrutinib	77 (53)
Venetoclax	46 (32)
Acalabrutinib	22 (15)
Comorbid conditions at baseline a	Acalabrutinib	Venetoclax	Ibrutinib
Hypertension	15 (69)	27 (59)	32 (42)
GERD	9 (41)	14 (30)	45 (31)
Atrial fibrillation/arrhythmia	5 (23)	12 (26)	9 (12)
Headache	3 (14)	0 (0)	4 (5)
Migraine	1 (5)	0 (0)	2 (3)
Genetic testing	n (%)
Del (13q)	77 (53)
Del (11q)	24 (17)
Del (17p)	15 (10)
No testing available	46 (32)

^a Results are not mutually exclusive; therefore, totals may exceed 100%.

CLL = chronic lymphocytic leukemia; GERD = gastrointestinal reflux disease; SLL = small lymphocytic leukemia.

ADHERENCE AND PERSISTENCE

Eight patients were excluded from the adherence and persistence analysis because of having less than 3 fills during the study period. Among the 137 patients with 3 or more fills (Figure 1), the median PDC was 0.98 (IQR 0.90-1.00) with a median observation window of 15 (8-32) months. A total of 51 patients (37%) were nonpersistent, with a median time to nonpersistence of 10 (IQR 6-19) months (Figure 2). Median follow-up time for the persistence calculation was 13 (9-31) months. Reasons for nonpersistence were disease progression (n = 22, 43%), adverse effects (n = 17, 33%), patient deceased (n = 4, 8%), and unknown (n = 11, 22%).

FIGURE 1.

Patient Adherence for Oral CLL/SLL Therapy (N = 137)

FIGURE 2.

Patient Persistence to Oral CLL/SLL Therapy (N = 137)

DISCONTINUATION AND SWITCHES

A total of 53 patients (37%) discontinued therapy and 25 patients (17%) had a switch in therapy. Adverse effects and disease progression were the most common reasons for discontinuation (49% and 47%, respectively) and switching (72% and 32%, respectively). See Table 2 for a breakdown of adverse effects leading to discontinuation by drug. The most commonly reported adverse effects (≥10%) that led to discontinuation were hypertension (n = 4, 15%), atrial fibrillation (n = 3, 12%), and bruising (n = 3, 12%). The most common adverse effects (≥10%) reported in patients who were switched were bruising (n = 6, 24%), rash (n = 5, 20%), diarrhea (n = 5, 20%), nausea (n = 4, 16%), atrial fibrillation (n = 4, 16%), and thrombocytopenia (n = 4, 16%). Of the 145 patients included in the study, 28 (19%) completed treatment during the study period.

TABLE 2.

Adverse Effects by Drug

All adverse effects (reported at the adverse effect level)	Acalabrutinib, n (%) (n = 14)	Ibrutinib, n (%) (n = 134)	Venetoclax, n (%) (n = 47)
Rash	2 (14)	24 (18)	5 (11)
Bruising	1 (7)	27 (20)	0 (0)
Nausea	2 (14)	8 (6)	10 (21)
Fatigue	0 (0)	11 (8)	6 (13)
Diarrhea	3 (21)	10 (7)	3 (6)
Myalgia	0 (0)	8 (6)	1 (2)
Thrombocytopenia	0 (0)	3 (2)	5 (11)
Hypertension	1 (7)	6 (5)	0 (0)
Atrial fibrillation	0 (0)	6 (5)	1 (2)
Headache	2 (14)	2 (2)	2 (4)
Other	3 (21)	29 (22)	14 (30)
Most common adverse effects leading to discontinuation (n = 26)	Acalabrutinib n  =  2	Ibrutinib n  =  20	Venetoclax n  =  4
Atrial fibrillation	0 (0)	3 (15)	0 (0)
Bruising	1 (50)	2 (10)	0 (0)
Fatigue	0 (0)	2 (10)	0 (0)
Nail Splitting	0 (0)	2 (10)	0 (0)
Rash	0 (0)	2 (10)	0 (0)
Diarrhea	1 (50)	0 (0)	0 (0)
Pancytopenia	0 (0)	0 (0)	1 (25)
Neutropenia	0 (0)	0 (0)	2 (50)
Nausea	0 (0)	0 (0)	1 (25)
Other a	0 (0)	10 (50)	0 (0)

^a Other adverse effects include esophagitis, hypertension, irregular heart palpitations, myalgia, persistent dermatitis, and supraventricular tachycardia.

PHARMACIST INTERVENTIONS

There were 69 patients who had at least 1 intervention (43%). There were 99 interventions related to adverse effects for ibrutinib (70%), 15 interventions for acalabrutinib (11%), and 27 interventions for venetoclax (19%). Actions taken by the pharmacist as part of the intervention (n = 141) are shown by therapy in Figure 3. Reviewing/updating the patient’s chart in the EHR (n = 85, 60%) and counseling the patient (n = 50, 35%) were the most common actions. Outcomes due to the actions included identified issue resolved (no further action required) (n = 79), follow-up care scheduled (n = 9), medication administration held (n = 2), dose adjustment made (n = 4), or medication discontinued (n = 4). Please see Supplementary Figure 1 ^{(234.4KB, pdf)} for a breakdown of outcomes results for patients included in each analysis.

FIGURE 3.

Pharmacist Intervention Actions and Outcome Drug

Discussion

This study found that patients receiving CLL/SLL therapy at an IHSSP frequently require treatment discontinuation or switching but showed high adherence to therapy. Adverse effects were a common reason for discontinuation and nonpersistence and almost half of the patients required pharmacist interventions, highlighting the benefit of the IHSSP model for patients with CLL/SLL receiving oral oncolytic therapy.

Higher medication adherence has been proven to increase progression-free survival in patients with CLL/SLL and reduce the burden of care for these patients. ^{14 – 16} Although there are clear benefits of oral oncolytic therapy, such as fewer patient trips to the hospital or outpatient clinic visits for infusions, ensuring adherence to treatment in the outpatient setting can be challenging. ⁹ Previous literature has shown the benefits pharmacists can have on adherence to oral chemotherapy. ⁹ As part of routine care in the IHSSP model, patients are evaluated at least monthly and pharmacists use patient-reported data, along with clinical data in the EHR such as laboratory results, to perform interventions or refer patients for follow-up. Unique characteristics of this model, such as frequent follow-up and integration with the EHR and care team, likely contribute to the high rate of adherence to oral CLL therapy despite experiencing frequent adverse effects, though additional comparative studies are needed to confirm the impact of the model on adherence.

Nonpersistence was seen in 37% of patients in the study over a median follow-up of 13 months. Common reasons for nonpersistence were disease progression (43%) and adverse effects (33%), which is consistent with other literature. ¹⁷ Most holds or changes in therapy are necessary because of adverse effects or disease progression. Although disease progression may necessitate changing therapy, adverse effects have the potential to improve if there is a stoppage and reintroduction to therapy, a dose decrease is indicated, or a mitigation strategy is provided. If a patient is achieving a benefit from therapy, all potential adverse effect strategies should be considered. ¹⁷

Recent studies have shown that BTKi therapy is less tolerable in a real-world setting than in a clinical trial setting. ¹⁸ Patients in this real-world study experienced adverse effects leading to switches in 17% of patients and discontinuations in 36% of patients. In the clinical trial setting with ibrutinib, 4%-10% of patients discontinued therapy and 9% of patients experienced dose reductions because of adverse effects. ⁵ Similarly, acalabrutinib was discontinued in 10%-11% of patients and dose reduced in 3.9%-7% of patients because of adverse effects in the clinical trial setting. ³ For venetoclax (trial data reported with combination therapy), adverse effects led to 16% of patient discontinuations and 13%-15% of dose reductions in the clinical trial setting. ⁴ Discontinuations were more common in the current real-world settings, potentially because of multiple treatment options being available in the real-world for patients to switch to if adverse effects were too challenging. Because almost half of discontinuations were driven by adverse effects, specialty pharmacist involvement in therapy monitoring and management is important to optimize these treatment options.

The type of adverse effects experienced by patients can be seen in Table 2. The most common adverse effect that led to discontinuation for ibrutinib was atrial fibrillation. Atrial fibrillation rates in patients taking ibrutinib are estimated at 3%-16% and remain a significant challenge to therapy requiring a multidisciplinary approach to management. ^{19 , 20} IHSSP pharmacists perform pretreatment assessment reviews and can identify patients with preexisting atrial fibrillation or other comorbid conditions that could increase patient risk for adverse effect and ensure prescriber awareness and appropriate monitoring. ²¹ For acalabrutinib, the most common adverse effects that led to discontinuation were bruising and diarrhea. Bruising could be an indication of thrombocytopenia, neutropenia, or anemia, as reported in the adverse effect profile and may require the patient to have laboratory work completed. ² Pharmacists can help provide mitigation strategies for diarrhea, such as loperamide and adequate hydration (or notify provider if severe), at therapy initiation and at the time when patients are anticipated to experience diarrhea. Lastly, the most common adverse effect causing venetoclax discontinuation was myelosuppression, which aligns with previous studies showing rates of neutropenia, thrombocytopenia, and anemia around 29%-64%. ³ Myelosuppression can also pose challenges, but pharmacists can ensure patients complete appropriate laboratory monitoring to identify this adverse effect early and determine therapeutic options. Overall, the adverse effects observed in this study population are similar to common adverse effects listed for these medications.

IHSSP pharmacists commonly intervened to address and mitigate adverse effects from oral oncolytic treatment, such as rash, bruising, nausea, fatigue, and diarrhea. The most common interventions were reviewing or updating the patient’s chart, counseling the patient, or referring the patient to their provider. Patient counseling often included review of medication dosing and administration, adverse effects and mitigation strategies, what to do in case of a missed dose, when to contact a health care provider, and the importance of follow-up for clinic appointments. Within the IHSSP, pharmacists may counsel patients at clinic visits with their provider, through the EHR patient portal, or by phone. Providing multiple communication modalities for patients to connect with the pharmacy team and clinic is useful to promote patient engagement. Though most pharmacist interventions led to the identified issues being resolved without therapy adjustment, some resulted in a medication or dose change or in follow-up care being scheduled, highlighting the important role an integrated pharmacist can play in overall specialty therapeutic management. Monthly patient follow-up evaluating for adverse effects ensures any potential issues are identified and addressed quickly. As the IHSSP has direct access to patients’ EHR, communication regarding patient concerns or adverse effects may be relayed directly to the health care provider, increasing continuity of care. ²² Specialty pharmacies that do not have access to the EHR cannot see the real-time changes and clinic notes documenting updates on a patient. IHSSPs can use EHR data to help improve patient care, reduce potential gaps in care, and collaborate with the health care team.

LIMITATIONS

This study has several limitations. First, this study was conducted at a single site with a small sample size. Comparing the results of this study to other IHSSP practice models could further strengthen the understanding of the benefits of embedding specialty pharmacists in oncology and hematology clinics. Second, the findings from this study were not compared with non-IHSSPs (ie, traditional specialty pharmacies) that do not usually have access to a patient’s EHR to potentially provide interventions for patients. Next, this study did not collect the amount of pharmacists’ time for each intervention. Future studies are warranted to quantify pharmacists’ time for interventions for adverse effect management. Lastly, newer agents for the treatment of CLL/SLL were approved during the study period and were not included.

Conclusions

Adherence to oral oncolytic therapy was high and reasons for nonpersistence and discontinuation were mostly related to adverse effects or disease progression in patients receiving CLL/SLL therapy through an IHSSP. Adverse effects contributed to therapy discontinuations and therapy switches, which occurred at a higher rate than what was seen in the clinical trials, indicating a continued opportunity for specialty pharmacists to help manage and mitigate adverse effects. Pharmacists commonly managed those adverse effects by counseling patients, which led to most of the identified issues being resolved. Future studies should continue to analyze the role of pharmacists and their impact on specialty medication use.

Funding Statement

The project described was supported by CTSA awards No. UL1 TR002243 and UL1 TR000445 from the National Center for Advancing Translational Sciences. Its contents are solely the responsibility of the authors and do not necessarily represent official views of the National Center for Advancing Translational Sciences or the National Institutes of Health.