Real-World Use and Acceptance of Biosimilar Monoclonal Antibodies of Rituximab in Oncology Practice in the USA

Abstract

Aim: To describe treatment patterns and patient and provider characteristics associated with the recently introduced biosimilar rituximab-pvvr. Methods: This retrospective analysis included adult patients with one or more claims for rituximab-pvvr, with an index date of 23 January 2020 and a study period covering 1 January 2019–31 July 2020. Results: Of 249 patients included, the most common rituximab-pvvr indications were non-Hodgkin’s lymphoma (77.5%) and chronic lymphocytic leukemia (11.2%). Some patients with non-Hodgkin’s lymphoma (42.5%) and chronic lymphocytic leukemia (39.3%) switched to rituximab-pvvr from the reference product or another rituximab biosimilar. Most patients were aged ≥65 years (63.5%) and were male (54.6%). Most (59.0%) rituximab-pvvr prescribers practiced in the south of the USA. Conclusion: Utilization occurred in approved and extrapolated indications. These preliminary findings suggest switching between reference product and rituximab biosimilars; rituximab-pvvr combination regimens are being adopted in real-world oncology practice.

Lay abstract

A biosimilar is a biological medication that is highly similar in structure and function to a biological medication already approved by the US FDA – the ‘original biologic’. The first biosimilars approved to treat certain blood cancers have become available in the USA. This study examined how a recently introduced rituximab biosimilar was being utilized, looking at patient and physician characteristics from a medical and prescription insurance claims database. This study did not examine the safety or effectiveness of this medication. While initial data are limited, the biosimilar, rituximab-pvvr, appears to be utilized to treat the same types of cancer as the original biologic, rituximab. The biosimilar was most frequently prescribed for non-Hodgkin’s lymphoma and chronic lymphocytic leukemia.

Keywords::

• biosimilars
• chronic lymphocytic leukemia
• monoclonal antibodies
• non-Hodgkin’s lymphoma
• oncology
• rituximab-pvvr

A biosimilar is a biological medical product demonstrated to be highly similar to an existing US FDA-approved biologic, the ‘reference medicine’ [1]. A biosimilar is similar to its reference product in terms of its structure, function, clinical immunogenicity, clinical safety, and effectiveness [2]. Once similarity with the reference product is established, the FDA approves at least one indication of the reference product to be listed as an indication for the biosimilar [3]. The introduction of biosimilars in oncology has the potential to increase treatment access and to reduce direct spending on biological drugs by US$44 billion over a 10-year period [4–6].

Rituximab was the first monoclonal antibody that received approval for treatment of B-cell non-Hodgkin’s lymphoma (NHL) [7]. Over the years, rituximab has also become part of a standard of care for the treatment of chronic lymphocytic leukemia (CLL) [8,9]. Furthermore, combination therapy with rituximab has demonstrated improved clinical outcomes in patients with diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL) [10,11].

As of November 2020, there are two FDA-approved rituximab biosimilars that were licensed in the USA under section 351(k) of the Public Health Service Act. Clinical trials demonstrated equivalent pharmacokinetics, as well as comparable safety and efficacy, for rituximab biosimilars in FL [12]. Two rituximab biosimilars (rituximab-abbs [Truxima^®] and rituximab-pvvr [Ruxience^®]) received FDA approval for all the approved oncology indications of the rituximab reference medication, including those utilizing monotherapy and combination therapies [13,14]. Furthermore, the FDA approvals included indications not studied in comparative clinical trials of the biosimilar; rather, they are extrapolated with scientific justification, utilizing the totality of the evidence known about the reference medication and the biosimilar [2,15]. Due to the limited number of clinical trials being conducted, real-world evidence can potentially uncover knowledge gaps and provide insights on the acceptance and manner of use of rituximab biosimilars by key stakeholders, including physicians, pharmacists, and patients [16].

In this regard, an important component of acceptance in clinical practice is the perception and confidence clinicians have for biosimilars. Healthcare providers from the USA and Europe have reported safety, efficacy, extrapolation of indications, and interchangeability as determinants of the acceptance of biosimilars [17]. However, a recent study based on German medical records showed that rituximab biosimilars were widely used in several indications, including DLBCL, FL, mantle cell lymphoma, marginal zone lymphoma and CLL [18]. Furthermore, rituximab biosimilars were found to be used in combination regimens in a manner consistent with the reference medicine [18]. These results were suggestive of greater acceptance of rituximab biosimilars.

Although prior studies have examined the acceptance of biosimilars in the USA, there are limited data on rituximab biosimilars in an oncology setting [17,19,20]. Furthermore, there are no data available on rituximab-pvvr, a rituximab biosimilar approved by the FDA on 23 July 2019 for the treatment of NHL, CLL, granulomatosis with polyangiitis, and microscopic polyangiitis [1]. Thus this study was designed to present preliminary real-world evidence on the patient characteristics, provider characteristics, and patterns of utilization associated with rituximab-pvvr in US clinical oncology practice.

Methods

Study design & data source

This retrospective study was conducted using US medical and prescription claims (open and closed) data covering the period between 1 January 2019 (i.e., a 1-year look-back window prior to the US commercial launch in January 2020) and 31 July 2020. Claims data were obtained from Komodo Health, a healthcare technology company whose databases contain >65 billion clinical, pharmacy and lab prescription and/or medical claims for >320 million individuals (covering the period 2012–2020). These encounters ensure that the data are highly representative of the patient population, including demographics (e.g., age, geography, risk pools), hospital and physician networks, healthcare claim processing companies (i.e., claims clearing houses), pharmacies, and health insurers. Nearly half of the claims database is comprised of ‘payer-complete’ datasets (i.e., closed claims), which come directly from the insurer and therefore tend to have more accurate and complete information in all claims data fields, but they also tend to have a delay in availability due to the process of insurer adjudication. Open claims, which are claims that have been submitted for adjudication to insurers (and not from insurers themselves), tend to have less complete information, but are essentially available in the data immediately. Komodo’s ‘payer-complete’ population includes prescription and/or medical claims of >140 million patients collected from >150 private insurers in the USA, including Medicaid Managed Care and Medicare Advantage plans. Further details on the Komodo Health claims database have been reported in prior studies [21–23]. National Provider Identifier codes from the claims data were used to determine the characteristics of those providers who prescribed rituximab-pvvr (or rituximab reference medication in exploratory analysis) to the patients included in the sample.

All medical and pharmacy claims data were Health Insurance Portability and Accountability Act compliant. Data with small sample sizes (counts ≤10 patients) were not reported, per the requirements of the Act. The study protocol was determined to be exempt from expedited or full ethics review by Pearl IRB (IN, USA; protocol: 20-KANT-236).

Inclusion criteria

Patients were considered eligible for inclusion in the present analysis if they were: aged ≥18 years, resided in the USA, had a billable national drug code indicating one or more uses of rituximab-pvvr within the claims database and had adequate claims-based information to assign an applicable diagnosis cohort (approved indication, oncologic, or other off label) using all medical and prescription claims from 360 days pre-index through the end of the study observation period (31 July 2020). Index treatment date was defined as the first claim date for rituximab-pvvr (23 January 2020). Patients who had a billable national drug code indicating one or more uses of rituximab reference medication within the claims database on or after the earliest index date for rituximab-pvvr were considered for an exploratory comparison to ensure patients and providers had an equivalent opportunity to use or prescribe either rituximab-pvvr or the rituximab reference medication.

Patient & provider characteristics

The current study collected data on patient and provider characteristics, as well as treatment utilization patterns for rituximab-pvvr. Patient characteristics, including age, gender, region of residence, payer type, and treatment-related diagnosis, were collected. Provider characteristics, such as specialty (internal medicine, hematology oncology, medical oncology, or other specialty) and region of practice (midwest, northeast, south, or west), were collected. Treatment characteristics, such as index dose amount, average dose amount, dosing schedule, duration of treatment, time to rituximab-pvvr initiation, and time to therapy initiation were collected (detailed definitions are provided in Supplementary Table 1). Additionally, data on treatment before receiving rituximab-pvvr, treatment in combination with rituximab-pvvr, and treatment post-rituximab-pvvr were collected.

Statistical analysis

Descriptive statistics were reported for all patient and provider characteristics for the aggregate sample of rituximab-pvvr users. Descriptive statistics for treatment utilization patterns were reported for the subset of patients with the most common indications observed for rituximab-pvvr. Continuous variables were reported as means and standard deviations or as medians, and categorical variables were reported as frequencies and percentages.

An exploratory analysis was conducted to evaluate whether patient and provider characteristics were similar for rituximab-pvvr and the rituximab reference medication. This analysis was restricted to the most common indications observed for rituximab-pvvr. Chi-square tests were used to conduct these comparisons; p-values <0.05 (two-tailed) were considered statistically significant for these comparisons. All analyses were performed using SAS^® Version 9.4 (SAS Institute Inc., NC, USA).

Results

Patient & provider characteristics

Baseline characteristics were reported for 249 patients treated with rituximab-pvvr (Table 1). A majority of patients treated with rituximab-pvvr were aged ≥65 years (63.5%), male (54.6%), and resided in the south (54.2%). Most providers who prescribed rituximab-pvvr specialized in hematology oncology (54.2%) or medical oncology (22.9%). A majority of providers prescribing rituximab-pvvr were in practice in the south (59.0%). The most common diagnoses associated with use of rituximab-pvvr were NHL (n = 193; 77.5%) and CLL (n = 28; 11.2%).

Table 1. Patient and provider characteristics.

Variables	n (%)
Age (years):
– <40	15 (6.0)
– 40–49	^†
– 50–59	38 (15.3)
– 60–64	28 (11.2)
– ≥65	158 (63.5)
Gender:
– Female	113 (45.4)
– Male	136 (54.6)
Region:
– Midwest	61 (24.5)
– Northeast	15 (6.0)
– South	135 (54.2)
– West	38 (15.3)
Insurance:
– Commercial	44 (17.7)
– Medicare	42 (16.9)
– Medicaid	13 (5.2)
– Other	^†
– Missing	148 (59.4)
Provider type (index):
– Internal medicine	15 (6.0)
– Oncology, hematology	135 (54.2)
– Oncology, medical	57 (22.9)
– Other	22 (8.8)
– Missing	20 (8.0)
Provider region (index):
– Midwest	51 (20.5)
– Northeast	14 (5.6)
– South	147 (59.0)
– West	17 (6.8)
– Missing	20 (8.0)
Diagnosis:
– Non-Hodgkin’s lymphoma	193 (77.5)
– Chronic lymphocytic leukemia	28 (11.2)
– Granulomatosis with polyangiitis	^†
– Microscopic polyangiitis	^†
– Other diagnosis	17 (6.8)

† Counts were ≤10 patients and could not be reported.

Patients with NHL

Before initiation of index treatment with rituximab-pvvr, 48.7% of the patients with NHL received chemotherapy, and 42.5% received either rituximab reference medication or another rituximab biosimilar (Table 2). Nearly two-thirds (63.2%) of the patients with NHL were concurrently treated with chemotherapy and rituximab-pvvr. Combination regimens observed among patients with NHL included rituximab-pvvr + cyclophosphamide + doxorubicin + vincristine ± prednisone (33.2%) and rituximab-pvvr + bendamustine (15.0%). Additional data on rituximab-pvvr treatment utilization characteristics among patients with NHL, including index dose, dosing schedule, time to therapy initiation, time to biosimilar initiation, and duration of therapy, are shown in Supplementary Table 2.

Table 2. Treatment pattern for patients with non-Hodgkin’s lymphoma.

Treatment	Treatment pre-rituximab-pvvr, n (%)	Concurrent treatment, n (%)
Pharmacological	120 (62.2)	122 (63.2)
Radiation	^†	NA
Surgery	NA	NA
Pharmacological :
– Chemotherapy	94 (48.7)	122 (63.2)
– Immunotherapy	^†	^†
– Targeted therapy	^†	^†
– Any rituximab	82 (42.5)	NA
– Rituximab (Rituxan^®)	79 (40.9)	NA
– Rituximab-abbs (Truxima^®)	^†	NA
Chemotherapy:
– Dexamethasone	72 (37.3)	99 (51.3)
– Prednisone	51 (26.4)	33 (17.1)
– Cyclophosphamide	27 (14.0)	68 (35.2)
– Vincristine	27 (14.0)	69 (35.8)
– Doxorubicin	26 (13.5)	66 (34.2)
– Bendamustine	19 (9.8)	29 (15.0)
– Etoposide	^†	^†
– Methotrexate	^†	NA
– Carboplatin	^†	^†
– Cisplatin	^†	NA
– Cytarabine	^†	^†
– Gemcitabine	^†	NA
– Ifosfamide	^†	NA
Immunotherapy:
– Polatuzumab vedotin	^†	^†
– Lenalidomide	^†	NA
– Obinutuzumab	^†	NA
Targeted therapy:
– Bortezomib	^†	^†
– Ibrutinib	^†	NA
Combination regimens:
– Rituximab + bendamustine	NA	29 (15.0)
– Rituximab + cyclophosphamide + doxorubicin + vincristine + prednisone^‡	NA	64 (33.2)

† Counts were ≤10 patients and could not be reported.

‡ With prednisone: 20 (10.4%); without or missing prednisone: 44 (22.8%).

NA: Not available.

Patients with CLL

Before initiation of index treatment with rituximab-pvvr, 60.7% of patients with CLL received chemotherapy, while 39.3% received either rituximab reference medication or another rituximab biosimilar (Table 3). Half of the patients (50.0%) with CLL were concurrently receiving chemotherapy in combination with rituximab-pvvr. Further details on the treatment utilization characteristics of rituximab-pvvr among patients with CLL are provided in Supplementary Table 2.

Table 3. Treatment pattern for patients with chronic lymphocytic leukemia.

Treatment	Treatment pre-rituximab-pvvr (n = 22), n (%)	Concurrent treatment (n = 14), n (%)
Pharmacological	22 (78.6)	14 (50.0)
Radiation	NA	NA
Surgery	NA	NA
Pharmacological:
– Chemotherapy	17 (60.7)	14 (50.0)
– Immunotherapy	^†	NA
– Targeted therapy	^†	^†
– Any rituximab	11 (39.3)	NA
– Rituximab (Rituxan^®)	^†	NA
– Rituximab-abbs (Truxima^®)	^†	NA
Chemotherapy:
– Dexamethasone	11 (39.3)	12 (42.9)
– Bendamustine	^†	^†
– Prednisone	^†	^†
– Cyclophosphamide	^†	^†
Immunotherapy:
– Obinutuzumab	^†	NA
Targeted therapy:
– Ibrutinib	^†	^†
Combination regimens:
– Rituximab + bendamustine	NA	^†

† Counts were ≤10 patients and could not be reported.

NA: Not available.

Exploratory analysis

Among patients with NHL and CLL, comparisons between rituximab-pvvr and rituximab reference medication showed statistically significant differences in region of residence (p < 0.001). Patients using rituximab-pvvr more often resided in the south (57.9 vs 34.1%), whereas those receiving rituximab reference medication more often resided in the northeast (18.4 vs 6.8%). Differences were also observed in provider type (p < 0.001) and region of practice (p < 0.001). Rituximab-pvvr prescribers more often specialized in hematology oncology (58.4 vs 36.3%) and were in practice in the south (62.9 vs 26.6%), compared with prescribers of rituximab reference medication (Table 4).

Table 4. Exploratory analysis comparing patient and provider demographics between rituximab-pvvr and rituximab reference medication.

Variables	Rituximab-pvvr (n = 221), n (%)	Rituximab (n = 7100), n (%)	p-value
Age (years):
– <40	12 (5.4)	360 (5.1)	0.056
– 40–49	^†	431 (6.1)
– 50–59	28 (12.7)	1,107 (15.6)
– 60–64	25 (11.3)	923 (13.0)
– 65+	151 (68.3)	4279 (60.3)
Gender:
– Female	95 (43.0)	3074 (43.3)	0.927
– Male	126 (57.0)	4026 (56.7)
– Missing^‡	NA	NA
Region:
– Midwest	50 (22.6)	1852 (26.1)	< 0.001
– Northeast	15 (6.8)	1307 (18.4)
– South	128 (57.9)	2424 (34.1)
– West	28 (12.7)	1484 (20.9)
– Missing^‡	NA	33 (0.5)
Insurance:
– Commercial	40 (18.1)	1861 (26.2)	0.225
– Medicare	39 (17.6)	1467 (20.7)
– Medicaid	^†	686 (9.7)
– Other	^†	132 (1.9)
– Missing^‡	131 (59.3)	2954 (41.6)
Provider type (index):
– Internal medicine	14 (6.3)	774 (10.9)	< 0.001
– Oncology, hematology	129 (58.4)	2579 (36.3)
– Oncology, medical	56 (25.3)	1643 (23.1)
– Other	^†	390 (5.5)
– Missing^‡	19 (8.6)	1714 (24.1)
Provider region (index):
– Midwest	40 (18.1)	1492 (21.0)	< 0.001
– Northeast	14 (6.3)	972 (13.7)
– South	139 (62.9)	1888 (26.6)
– West	^†	1022 (14.4)
– Missing^‡	19 (8.6)	1726 (24.3)

† Counts were ≤10 providers and could not be reported.

‡ Observations with ‘missing’ excluded prior to significance testing.

NA: Not available.

Discussion

This retrospective study reported a preliminary assessment of the real-world adoption of the recently introduced biosimilar, rituximab-pvvr, in the US oncology setting. Most patients who received treatment with rituximab-pvvr were older than 65 years. We observed that more than one-half of the eligible patients resided in the south, and over three-quarters of providers who prescribed rituximab-pvvr were oncologists. Rituximab-pvvr was primarily used for treating patients with NHL and CLL, which was suggestive of initial acceptance of this biosimilar in these indications. An exploratory analysis indicated significant differences between rituximab-pvvr and rituximab reference medication in patient-specific characteristics (in terms of region of residence) and all provider characteristics. These findings can potentially provide insights for payers about the patient and provider profiles associated with rituximab-pvvr in US clinical practice, particularly among early adopters of this biosimilar.

We observed that some patients switched from rituximab reference medication or another rituximab biosimilar to rituximab-pvvr, and they were often administered rituximab-pvvr as part of a combination regimen. While clinical and safety outcomes could not be evaluated in the current study, a prior systematic review including 90 studies and data from 14,225 patients across multiple biosimilar medications reported no differences in terms of immunogenicity, safety, or efficacy following a switch from a reference medication to a biosimilar [24]. The switch rate to rituximab-pvvr from any other rituximab product was up to 2.5-times higher for patients with NHL and CLL in the current study than the approximately 17.0% switch rate to rituximab-abbs from the rituximab reference product among patients with DLBCL reported in a prior real-world study [25]. Notably, a Phase III randomized controlled trial in which 36.9% of patients with rheumatoid arthritis were switched from the rituximab reference product to rituximab-abbs found no differences between treatment groups in safety and efficacy end points [26]. However, head-to-head comparisons between rituximab biosimilar products, standardizing the indications of interest and methodology, would be required to ascertain whether any practically meaningful differences exist between these biosimilars in terms of their clinical outcomes and treatment patterns. Although rituximab-pvvr was only recently introduced to market, our preliminary results suggest that this medication is being accepted in US oncology practice and is being used in a manner consistent with clinical guidelines in which the use of rituximab is recommended as part of a combination regimen with chemotherapy, targeted therapy, or immunotherapy [27,28]. However, patient- or provider-specific characteristics or reasons for switching from a reference or other biosimilar to rituximab-pvvr would need to be assessed in future studies.

Differences in patient and provider characteristics were observed between rituximab-pvvr and rituximab reference medication. While the data did not allow us to discern the underlying reasons for these differences, it is possible that external factors could play a role. For instance, medication reimbursement and billing policies, supply chain considerations, and legal considerations, among other factors, could potentially inhibit the broader adoption of biosimilars in the US oncology setting [4,16]. Market access strategies may also account for these observed differences, as early adopters of rituximab-pvvr may not be representative of the broader patient and provider populations who use or prescribe the rituximab reference medication.

Our preliminary findings are consistent with those of a real-world study conducted to understand acceptance of rituximab biosimilars in the German healthcare system. Using rituximab biosimilar alone or in combination regimens for the treatment of NHL and CLL was in accord with German electronic medical record data [18]. Furthermore, in that study, prescriptions for rituximab biosimilars increased sevenfold over 24 months [18]. As rituximab-pvvr was only recently introduced in the USA, we could not analyze longitudinal trends in uptake in the current study; further research will be needed to evaluate utilization trends over a longer period.

Cancer treatment is one of the main drivers of healthcare costs [29]. The overall cost of cancer treatment is projected to increase by 34% between 2015 and 2030 in the USA [30]. The wider availability of biosimilars is anticipated to improve the cost–effectiveness of cancer treatment [5]. However, to realize these potential economic benefits, it is necessary to implement policies that encourage or incentivize biosimilar use at the government and payer levels for wider acceptance among healthcare providers and patients in the USA [16]. Furthermore, efforts will be needed to ensure that clinicians and patients receive appropriate education on the efficacy and safety of biosimilars, particularly in the oncology setting [31].

Our results should be interpreted in the light of relevant limitations. First, missing data and errors or inconsistencies in the coding of diagnoses, procedures, or treatments in claims data are possible. Additionally, patients can be lost to follow-up if they change insurance plans. Second, the claims data were representative of the insured US population; it is unclear whether similar trends would be observed among uninsured patients treated with rituximab-pvvr or rituximab reference medication. Our study aimed to describe preliminary real-world patterns of utilization for rituximab-pvvr. As such, the assessment of clinical outcomes or comparisons among rituximab biosimilar or reference products on clinical outcomes were not a focus of the current analysis, and future research would be needed to discern these issues. In exploratory analysis comparing rituximab-pvvr and the reference drug, the former group comprised only 3% of the sample; thus appropriate caution should be used in drawing inferences from these initial results. Assessment of reasons for switching, including safety issues, were outside the scope of analysis for the current study, and future research using patient medical records with a longer follow-up time will be required to further describe these factors. Lastly, we could not report data on treatment utilization patterns post-rituximab-pvvr index due to small sample sizes, and a longer follow-up time would be needed to make this assessment and to corroborate the results observed in these preliminary data.

Conclusion

This retrospective study provides initial evidence suggesting that extrapolation of indications in which rituximab reference medication was approved by the FDA and switching from rituximab reference medication or another rituximab biosimilar to rituximab-pvvr alone or in combination with chemotherapy, targeted therapy or immunotherapy is being accepted in US oncology practice. There is a need for additional data with longer follow-up periods to explore clinical outcomes and cost–effectiveness in various patient populations who may be prescribed rituximab biosimilars.

Summary points

• Biosimilars are anticipated to improve treatment access and reduce costs associated with cancer treatment.

• The recently introduced biosimilar monoclonal antibody rituximab-pvvr is US FDA approved for use in reference product cancer indications.

• This retrospective analysis of pharmacy claims data, covering the period between 1 January 2019 and 31 July 2020, included 249 patients aged ≥18 years with one or more claims indicating usage of the rituximab-pvvr biosimilar.

• Rituximab-pvvr was most commonly used for treating patients with non-Hodgkin’s lymphoma (NHL; n = 193, 77.5%) and chronic lymphocytic leukemia (CLL; n = 28, 11.2%).

• Rituximab-pvvr prescribers primarily specialized in hematology oncology (54.2%) and were in practice in the south of the USA (59.0%).

• Switching to rituximab-pvvr from the reference product or another rituximab biosimilar was observed in 42.5 and 39.3% of patients with NHL and CLL, respectively.

• Nearly two-thirds (63.2%) of patients with NHL and 50.0% of those with CLL were receiving chemotherapy in combination with rituximab-pvvr; rituximab-pvvr was also used concurrently with targeted therapy or immunotherapy.

• Exploratory analysis showed statistically significant differences in patient region of residence, as well as provider type and region of practice, when comparing rituximab-pvvr and the reference product.

• Given that rituximab-pvvr was only recently introduced in the USA, analysis of longitudinal trends in uptake and assessment of cost–effectiveness will require further research with a longer-term follow-up period.

Author contributions

All authors were responsible for study conception and design; J Thompson and M Maculaitis were responsible for acquisition of the data; J Thompson was responsible for data analysis; M Maculaitis was responsible for drafting the manuscript; all authors were responsible for revision of the manuscript.

Ethical conduct of research

The study protocol was determined to be exempt from expedited or full ethics review by Pearl IRB (Indianapolis, IN, USA; protocol: 20-KANT-236).

Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at: www.tandfonline.com/doi/suppl/10.2217/fon-2021-0618

Financial & competing interests disclosure

The study was sponsored by Pfizer, Inc. J Yang, J Kelton, J Alvir and A Shelbaya are employees and stockholders of Pfizer, Inc. J Thompson and M Maculaitis are employees of Kantar, which received funding from Pfizer for conducting and reporting on the study. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Medical writing support was provided by A Atre and S Kulkarni from Indegene Pvt. Ltd, which was funded by Pfizer, Inc.

Additional information

Funding

Medical writing support was provided by A Atre and S Kulkarni from Indegene Pvt. Ltd, which was funded by Pfizer, Inc