Pneumococcal Vaccination Practices in Patients With Multiple Sclerosis Receiving Anti-CD20 Monoclonal Antibodies After Pharmacy and Nursing Collaboration

Ocrelizumab and rituximab are monoclonal antibodies (mAbs) that target the CD20 antigen found on B cells, leading to B-cell lysis.^1,2 Ocrelizumab was approved by the United States Food and Drug Administration in 2017 for relapsing forms of multiple sclerosis (MS) as well as primary progressive MS in adults.¹ Rituximab is not United States Food and Drug Administration approved for MS; however, it has been used off-label for the treatment of MS for many years. Evidence suggests that ocrelizumab and other mAbs may have greater efficacy compared with self-injectable disease-modifying therapies, thus their use is becoming more common in patients with MS.³

Patients with depleted B cells from treatment with anti-CD20 mAbs are at an increased risk for infection while receiving this immunosuppressive therapy. The Centers for Disease Control and Prevention (CDC) recommends that all patients 6 years and older who are immunocompromised, including iatrogenic immunosuppression, receive vaccinations against pneumococcal diseases.⁴ At the time this study was completed there were 2 pneumococcal vaccines available in the United States, 13-valent pneumococcal conjugate vaccine (PCV13) and 23-valent pneumococcal polysaccharide vaccine (PPSV23), both of which are inactivated.⁴ The former contains 13 serotypes of Streptococcus pneumoniae, and the latter contains 12 of the same serotypes as found in PCV13 as well as 11 additional serotypes. It is recommended that immunocompromised patients receive PCV13 first and PPSV23 at least 8 weeks later.⁵ Although PPSV23 contains more serotypes of S pneumoniae, PCV13 is administered first because studies have shown that a greater immune response is achieved when administered in this sequence.⁶

The prescribing information for ocrelizumab indicates that all inactivated vaccines should be administered at least 2 weeks before the initiation of ocrelizumab infusions.¹ Guidance for rituximab extends this recommendation, stating that all inactivated vaccinations should be administered at least 4 weeks before initiating treatment.² Vaccinating patients before initiation allows time to develop an immune response to the disease before B-cell stores are diminished.

In 2014, the University of Rochester Specialty Pharmacy added a fully integrated clinical pharmacist dedicated to caring for patients at the University of Rochester Multiple Sclerosis Center (UR MS Center). There are now 2 clinical pharmacists integrated in the UR MS Center working closely with providers, nurses, social workers, and clinic support staff. Growth of clinical services provided by the integrated clinical pharmacists and expanded, specialized nursing positions fostered interdisciplinary working relationships and ultimately led to this collaborative project.

At the start of this medication use evaluation, there was not a standard procedure at the UR MS Center for tracking whether patients received pneumococcal vaccinations in the optimal timing and sequence before and after starting anti-CD20 mAb therapy. The purpose of this study was to evaluate adherence to CDC pneumococcal vaccination recommendations for patients with MS receiving ocrelizumab or rituximab at an MS center in an academic medical center before and after a nursing intervention.

METHODS

Study Design

This single-center, retrospective, pre/post medication use evaluation was granted institutional review board exemption.

Study Population

All individuals who received rituximab or ocrelizumab at the UR MS Center during the study periods were screened for inclusion. Patients were included if they were older than 18 years and received their first anti-CD20 mAb infusion at the study site. For the initial study period, all the participants had received their first dose or were scheduled to receive their first dose before September 20, 2019. For the follow-up evaluation, all the participants had received their first dose between February 1, 2020, and December 31, 2020. The electronic medical record (EMR) was reviewed to obtain demographic information, infusion dates, and vaccination dates for PCV13 and PPSV23.

Participants were considered to have received optimal vaccination sequence if they received PCV13 or PPSV23 as per CDC recommendations before their first anti-CD20 mAb infusion.^1,2,4,7 Subsequent pneumococcal vaccine administrations were collected to determine whether the optimal sequence was completed.

OUTCOMES

The primary study outcome was the difference between the number of patients receiving pneumococcal vaccination as recommended by the CDC within the recommended interval (≥2 weeks before starting ocrelizumab or ≥4 weeks before starting rituximab) before and after the nursing intervention. Secondary outcomes included percentage difference in patients who received follow-up vaccination after initial optimal pneumococcal vaccination before and after the nursing intervention, median difference in the number of days between receiving initial optimal pneumococcal vaccination and follow-up vaccination, and location of PCV13 administration preintervention and postintervention.

Nursing Workflow Preintervention and Postintervention

Before the nursing intervention there was no standardized procedure to monitor patients’ vaccination status in the UR MS Center. A nurse clinical care manager/educator position was created in the Multiple Sclerosis and Neuroimmunology Division of the Department of Neurology in March 2019; this nurse was responsible for coordinating pneumococcal vaccinations for patients starting B-cell–depleting disease-modifying therapy. If the dedicated nurse was not available, the triage nurse or an infusion nurse assumed this responsibility. All nurses involved with the intervention were registered nurses. Providers notified the nurse of the plan to initiate therapy during the office visit or via a routed office note describing the plan. Plan-Do-Study-Act cycles were used to establish an effective process.⁸ Plan-Do-Study-Act is a method of testing change in real work settings. Pilot testing may begin after a team is formed, measurable goals are established, and changes are identified. A series of cycles are required as learning occurs and refinements are made. Once there is a successful cycle, a broader-scale change is put into place. In February 2020, the nurse began contacting patients by phone or secure messages through the EMR. This practice was stopped after 2 weeks because it proved to be inefficient, and patients who were in the clinic were being missed. By mid-February 2020, first-dose vaccinations of PCV-13 were administered to patients in the clinic during scheduled office visits before initiation of B-cell–depleting therapy. Subsequent doses of PCV13 and PPSV23 were administered per the CDC guidelines without regard to the timing of the upcoming or postinfusion schedule. Patients received second- and third-dose vaccinations during their scheduled infusion appointments if they had tolerated 1 or more doses of rituximab or ocrelizumab. Using these same criteria, sequential PCV13 and PPSV23 doses were administered during follow-up office visits. If pneumococcal vaccine doses could not be administered in the clinic, the nurse would assist the patient in receiving the correct vaccine dose at the patient’s or insurance provider’s preferred location (eg, primary care physician’s office, local pharmacy) by coordinating with the neurology provider to prescribe the optimal pneumococcal vaccine.

Nursing interventions included reviewing the neurology infusion center schedule to identify patients, importing outside records from linked EMRs and the New York State Immunization Information System (NYSIIS), managing the clinic inventory of PCV13 and PPSV23, educating patients and obtaining NYSIIS consent during infusion appointments, requesting orders for and administrating vaccinations, and completing documentation.

During the early stages of the second study period, the burden of care and monitoring rested solely on the neuroimmunology clinical care manager/educator. To relieve that burden, the safety nurse was identified as additional support. A Training of Trainer model was used to explain the rationale, process, and documentation of patients requiring vaccinations.^9,10 The Training of Trainer model uses expert trainers to teach subject matter to novice trainers. Initial training is followed by discussion, listening, observation, and support. The novice trainer then becomes a subject matter expert and can train others in the same cyclical pattern.

Statistical Analyses

Analyses included t tests for numerical values and χ² tests for categorical variables; statistical significance was set at P < .05. Additional categorical data measures are described by a percentage or frequency of occurrence. Continuous data are reported using mean with SD or median with interquartile range (IQR), whichever was appropriate.

RESULTS

Population

A total of 444 patients were screened for inclusion in the preintervention analysis, and 406 were included. In the preintervention group the first rituximab infusion was administered in August 2013 and the first ocrelizumab infusion was in June 2017. In the postintervention analysis, 87 patients were screened, and 73 were included (FIGURE 1). In both the preintervention and postintervention analyses, most patients were initiated on ocrelizumab: 73% in the preintervention group and 92% in the postintervention group.

Study Design and Inclusion

Primary Outcome

In the preintervention and postintervention groups, 57.6% and 83.6% of patients, respectively, were confirmed to have received the optimal initial pneumococcal vaccination (P = .009) (TABLE 1). The percentage of patients with unknown vaccination status was 16.7% in the preintervention group and 2.7% in the postintervention group (P = .004). In the preintervention and postintervention groups, 25.6% and 13.7% of participants, respectively, were confirmed not to have received the initial optimal vaccination (P = .05).

Initial Pneumococcal Vaccination Status

Secondary Outcomes

After receiving the initial optimal PCV13, 9.0% of patients in the preintervention group and 55.7% in the postintervention group received the follow-up PPSV23 immunization (P < .001). For those who received optimal PCV13 followed by PCV23, the median interval difference was 480 days (IQR, 328–813 days) in the preintervention group and 119 days (IQR, 74–238 days) in the postintervention group. Administration of PCV13 occurred at the UR MS Center in 39% of participants before the nursing intervention and in 52% postintervention.

DISCUSSION

The nursing team intervention significantly improved adherence to CDC pneumococcal immunization recommendations for patients receiving anti-CD20 mAb therapy at the MS center. There was also a significant increase in patients who received follow-up PPSV23 after receiving initial optimal PCV13. In addition to the improvement in optimal vaccination practices, this study showed an increase in patients who received their immunizations at the MS center after the nursing intervention. This highlights the improved coordination of care from the nursing intervention as more patients were able to receive their immunizations at the MS center.

Immunizing patients at the clinic ensures that patients receive the correct sequence and clear documentation before their first dose of B-cell–depleting therapy. After establishing a standardized procedure, the safety nurse then assumed the responsibility of vaccinating patients in the neurology infusion center. Once the workflow was established, the remaining infusion center nurses were trained by the safety nurse to vaccinate per protocol. This provided the clinical care manager/educator with additional time to administer vaccines in the clinic during patient office visits. Implementation of this process allowed for expansion of the vaccination program. The nurses began to cover a second neurology ambulatory care clinic for patients receiving rituximab and other high-risk medications, a nurse schedule was created with the availability to schedule patients 4 days a week at times more convenient to the patients, and additional vaccinations were administered, including influenza, herpes zoster, and meningococcal.

As a retrospective medical record review medication use evaluation, this study was limited by the information documented in the EMR. In the preintervention group, there was a larger percentage of patients with unknown vaccination status; postintervention, this number significantly decreased because part of the intervention was to confirm and document immunizations before initiation of ocrelizumab or rituximab. Improvement in documentation practices may have contributed to the differences in vaccination statuses between preintervention and postintervention groups. This study was limited by a smaller cohort of patients in the postintervention analysis given a shorter study window, with approximately 6 years for the preintervention and 10 months for the postintervention study periods. In addition, fewer participants initiated therapy as a result of concerns about the safety of starting immunosuppressive therapy during the COVID-19 pandemic. A future direction to consider is examining whether a difference in vaccination rates is observed based on patient characteristics (eg, age, sex), type of MS, and/or previous treatments.

The project highlights the value of interdisciplinary team collaboration and coordination in the care of patients with MS. This collaboration led to improved patient care and safety.

PRACTICE POINTS

Management of the complex medications used to treat multiple sclerosis (MS) is optimally provided by a multidisciplinary team. Nurses in expanded, specialized roles are well positioned to collaborate with clinical pharmacists to add value to the team and provide high-quality MS patient care.

Multidisciplinary team collaboration between integrated clinical pharmacists and the nursing team in an MS center led to improved adherence to recommendations for pneumococcal immunizations in patients taking medications that increased their risk of infection.