Cost-efficiency analysis and expanded treatment access modeling of conversion to rituximab biosimilars from reference rituximab in Jordan

Abstract

Aim

To assess the cost-efficiency and expanded access of three rituximab biosimilars versus the reference rituximab from the perspective of the Jordanian national health payer.

Methods

A 1-year cost-efficiency and expanded access model of conversion from reference rituximab (Mabthera) to the approved biosimilars (Truxima, Rixathon, and Tromax) to assess five metrics: total annual cost to treat a hypothetical patient; head-to-head cost comparison; changes in patients’ access to rituximab; number-needed-to-convert (NNC) to provide an additional 10 patients access to a rituximab treatment; and relative amount of Jordanian Dinar (JOD) spent on rituximab options. The model included rituximab doses at 100 mg/10 ml and 500 mg/50 ml and considered both cost-saving and cost-wastage scenarios. Costs of treatments were based on the fiscal year 2022 tender prices received by the Joint Procurement Department (JPD).

Results

Rixathon was associated with the lowest average annual cost per patient (JOD2,860) across all six indications among all rituximab comparators, followed by Truxima (JOD4,240), Tromax (JOD4,365) and reference Mabthera (JOD11,431). The highest percentage of patient access to rituximab treatment (321%) was achieved when switching patients from Mabthera to Rixathon in the RA and PV indications. At four patients, Rixathon was associated with the lowest NNC to provide an additional 10 patients access to rituximab treatment. For each JOD1 spent on Rixathon, an additional JOD3.21 must be spent on Mabthera, an additional JOD0.55 on Tromax, and an additional JOD0.53 on Truxima.

Conclusion

Rituximab biosimilars were associated with cost savings in all approved indications in Jordan compared to reference rituximab. Rixathon was associated with the lowest annual cost, the highest percentage of expanded patient access for all six indications, and the lowest NNC providing 10 additional patients with access.

Keywords:

• Biosimilars
• cost-efficiency
• expanded access
• Jordan
• rituximab

JEL CLASSIFICATION CODES:

• H51
• H5
• H
• I15
• I1
• I

Introduction

The biological agent rituximab, a human/murine monoclonal antibody (mAb), was the first mAb approved in oncology in 1997 by the United States (US) Food and Drug Administration (FDA)¹. Its therapeutic value is derived from its high affinity and specificity for CD20, an antigen expressed on both normal and cancerous B-cells². Rituximab has gained multiple approvals to treat previously untreated follicular lymphoma (FL), refractory follicular lymphoma (RFL), diffuse large B-cell lymphoma (DLBCL), chronic lymphocytic leukemia (CLL), as well as rheumatoid arthritis (RA), granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA), and pemphigus vulgaris (PV).

Biological drugs, such as rituximab, have significantly advanced the treatment of various diseases, yet their high costs are burdensome on healthcare budgets worldwide. The patent expiration of some biological treatments has created an opportunity for the development and marketing of lower-priced biosimilar drugs. This has enabled patients to be treated at lower costs. In addition, as has been shown in previous European and US studies, the savings generated from biosimilar conversion can be applied to provide more patients with access to therapeutic and supportive cancer care on a budget-neutral basis^3–15.

Originator rituximab is marketed internationally under the brand names Rituxan and Mabtheraⁱ, depending on the market. The patent expired in 2012 in Europe and in 2016 in the US^1,16, after which several rituximab biosimilars were approved and released to the global markets under different names. This included Jordan, classified by the World Bank as an upper-middle-income country^17,18. With modest spending on health care¹⁹, adopting biological drugs has been an economic burden on its national budget in addition to its citizens’ out-of-pocket spending. In addition to the initial approval of originator rituximab (Mabthera); in July 2020, the Jordan Food and Drug Administration (JFDA) granted approvals for three Rituximab biosimilars (i.e. Truximaⁱⁱ, Rixathonⁱⁱⁱ, and Tromax^iv)²⁰.

With the regulatory requirement that biosimilars has be equivalent in efficacy relative to the reference product; economic evaluations such as cost-effectiveness analysis that compares differences in costs to differences in effect, simply do not apply since within a stated equivalence margin, both the reference and its biosimilars are considered equally effective, thus reducing the denominator of the incremental cost-effectiveness ratio to a statistical zero²¹. Hence, the economic value of biosimilars has been evaluated mainly by means of cost-efficiency analyses and expanded access simulations.

In cost-efficiency models, the value of biosimilars is examined versus biological originators in terms of direct financial savings that can be achieved from switching to biosimilars and associated increase in patient access to those biosimilars^11,12,14. Importantly, these savings can subsequently be used to provide expanded access of pharmacotherapy to additional patients on a budget neutral basis. In other words, allocative efficiency, in a given health care system can be achieved when the number of patients who access to treatment is maximized under the assumption of a neutral budget.

Several cost-efficiency analyses quantifying the clinical and economic value of different biosimilars have been performed, initially in Europe and later in the US^11,12,14. For instance, McBride et al. showed that the biosimilar pegfilgrastim-bmez, a growth factor used in the prophylaxis and management of chemotherapy-induced febrile neutropenia, increases the value of cancer care by reallocating the significant cost savings to expand access to growth factor to more patients or to provide more patients with anti-neoplastic therapy on a budget neutral basis¹¹. Another study showed that converting a panel of 20,000 patients to prophylaxis with pegfilgrastim-cbqv yields annual savings of $246.7 M¹². A third US study documented the marked cost-efficiency of the biosimilar trastuzumab-dkst relative to its biologic originator¹⁴. As a result, more patients with breast and stomach cancer could receive treatment on a budget-neutral basis¹⁴.

The present study is part of a series of cost-efficiency and expanded access analyses quantifying the clinical and economic value of different biosimilars, first in Europe, later in the US and now also including emerging markets, with Jordan being the first^3–15. We report here on a study that aimed to quantify the cost-efficiency and expanded treatment access of conversion to rituximab biosimilars from reference rituximab in Jordan. To our knowledge, this is the first cost-efficiency study of rituximab from the public (governmental) health payer perspective in Jordan (i.e. the Jordanian Ministry of Health) and the first such study outside high-income countries.

Methods

Model overview

In this study, a cost efficiency model was constructed to estimate the cost implications of treating with reference rituximab (Mabthera) and three biosimilars (Truxima, Rixathon and Tromax) into the Jordanian market. The costs of the doses 100 mg/10 ml and 500 mg/50 ml were used. The model took into consideration all the approved indications for these drugs. The analyses considered two scenarios. The first was a cost-saving scenario where both doses (100 mg/10 ml and 500 mg/50 ml) were combined and applied in each indication in a way that minimized wastage. The second scenario was a cost-wastage scenario where only 500 mg/50 ml dose was used to calculate the cost spent on each indication. Notably, the scenario of using only 100 mg/10 ml was not applied because it is not clinically practical as the lowest dose required is more than 500 mg for most indications.

Five metrics were calculated: (1) annual treatment cost for one hypothetical patient; (2) head-to-head annual cost comparisons; (3) changes in patients’ access to the rituximab options; (4) number-needed-to-convert to the rituximab biosimilars to gain 10 additional patients treated with rituximab; and (5) the relative monetary value spent on rituximab options.

Because of different treatment durations for each indication, a one-year time horizon was assumed as the cut-off for indications requiring treatment for more than one-year, such as follicular lymphoma (FL), granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA), and pemphigus vulgaris (PV). As for indications requiring less than one-year of treatment exposure, such as diffuse large B-cell lymphoma (DLBCL), chronic lymphocytic leukemia (CLL), and rheumatoid arthritis (RA), the model considers the clinically recommended duration of treatment. Moreover, this time horizon was selected because in Jordan, the public health sector considers the national procurement of drugs on a yearly basis, and our aim is to provide immediate tangible evidence for decision-makers.

Costs are based on government tender prices and presented in Jordanian Dinar (JOD) for the year 2022 (JOD1= US$1.41). Discounting was not applied because the model time horizon did not exceed one year. In the cost-wastage scenario, 16 (500 mg) vials used in the treatment of FL and DLBCL, 12 (500 mg) vials in CLL, 10 (500 mg) vials in GPA and MPA, 4 and 5 (500 mg) vials used in RA and PV, respectively. However, in the cost-saving scenario, 8 (500 mg) plus 16 (100 mg) vials used in the treatment of FL and DLBCL, 6 (500 mg) plus 22 (100 mg) vials in CLL, 8 (500 mg) plus 6 (100 mg) vials in GPA and MPA, in RA and PV there were no wastage as the dose needed was either 500 mg or 1000 mg. Details about treatment regimens for all indications are available in the supplementary material (Tables S1–S6). For the treatments that require dosing on the basis of Body Surface Area (BSA), a BSA of 1.78 m² was adopted.

Inputs

Table 1 shows the tender prices for all the available intravenously (IV) administered rituximab options bought by the Joint Procurement Department (JPD) and available to the public in Jordan²². The JPD performs national procurement of drugs and medical supplies for all public health sectors jointly thorough annual tenders.

Table 1. Model inputs.

Input (available doses of each treatment)	Estimate (JPD price)
Rixathon IV (Novartis)
100 mg/10 ml, 2 vials/package	JOD 130.11
500 mg/50 ml, 1 vials/package	JOD 234.86
Truxima IV (Hikma)
100 mg/10 ml, 2 vials/package	JOD 154.05
500 mg/50 ml, 1 vials/package	JOD 360.46
Tromax IV (MS Pharma)
100 mg/10 ml, 2 vials/package	JOD 178
500 mg/50 ml, 1 vials/package	JOD 365
Mabthera IV (Roche)
100 mg/10 ml, 2 vials/package	JOD 414.65
500 mg/50 ml, 1 vials/package	JOD 987.88

Abbreviations. JPD, Joint Procurement Department; JOD, Jordanian Dinar.

Analysis

Total annual cost to treat a hypothetical patient

The total annual cost to treat a hypothetical patient was calculated using Equations (1)(1) $$\begin{array}{l}Totalannualcostincost-savingscenario=\sum \left[Numberofvials\left(500mg\right)\right]Xcostpervial\\ +\sum \left[Numberofvials\left(100mg\right)\right]Xcostpervial\end{array}$$(1) and (2)(2) $$\mathit{Total}\mathit{annual}\mathit{cost}in\mathit{wastage}\mathit{scenario}=\sum \left[\mathit{Number}of\mathit{vials}\left(500mg\right)\mathit{needed}\mathit{for}1\mathit{year}\right]\times \mathit{cost}\mathit{per}\mathit{vial}$$(2) . Equation (1)(1) $$\begin{array}{l}Totalannualcostincost-savingscenario=\sum \left[Numberofvials\left(500mg\right)\right]Xcostpervial\\ +\sum \left[Numberofvials\left(100mg\right)\right]Xcostpervial\end{array}$$(1) was used to estimate the annual treatment cost for the cost-saving scenario and Equation (2)(2) $$\mathit{Total}\mathit{annual}\mathit{cost}in\mathit{wastage}\mathit{scenario}=\sum \left[\mathit{Number}of\mathit{vials}\left(500mg\right)\mathit{needed}\mathit{for}1\mathit{year}\right]\times \mathit{cost}\mathit{per}\mathit{vial}$$(2) was used to estimate the same metric for the cost wastage scenario: (1) $$\begin{array}{l}Totalannualcostincost-savingscenario=\sum \left[Numberofvials\left(500mg\right)\right]Xcostpervial\\ +\sum \left[Numberofvials\left(100mg\right)\right]Xcostpervial\end{array}$$(1) (2) $$\mathit{Total}\mathit{annual}\mathit{cost}in\mathit{wastage}\mathit{scenario}=\sum \left[\mathit{Number}of\mathit{vials}\left(500mg\right)\mathit{needed}\mathit{for}1\mathit{year}\right]\times \mathit{cost}\mathit{per}\mathit{vial}$$(2)

Head-to-head cost comparisons

Pair-wise comparisons were performed between the rituximab options in all indications. In these comparisons, the direct subtraction method was used to estimate the savings from the adoption of lower-cost options as follows: (3) $$Annualsavings=annualtreatmentcostusingdrugA-annualtreatmentcostusingdrugB$$(3)

Where drug A represents the drug with a higher cost and drug B represents the drug with a lower cost.

Changes in patient access to rituximab

Switching patients from a high-cost option to a lower-cost option leads to cost savings. These savings can be reallocated to treat more patients with the lower-cost option. This approach was previously used in a budget impact study conducted in Saudi Arabia by Alkhatib et al. in which changes in diabetic patients’ access to peptide-1 receptor agonists (GLP1 agonists) was estimated²³. In our study an increase in patients’ access to rituximab due to switching patients from a higher-cost option to a lower-cost option was calculated using the following equation: (4) $$\%Changeinpatients’access=\left(savingsfromtheswitchingfromdrugAtodrugB\right)/\left(treatmentcostusingdrugB\right)X100$$(4)

Where drug A represents the higher-cost option and drug B represents the lower-cost option.

Number-needed-to-convert (NNC) to the most cost-efficient drug

In this study, NNC is the number of patients that need to be converted from a higher-cost option to a lower-cost option to expand the treatment coverage for a specified number of additional patients. Because the cost differences in the denominators were higher than the numerators will lead to having decimal points in the NNC, the NNC is estimated based on an additional 10 patients treated with the lowest cost Rituximab. The NNC method used in our study was based on McBride et al. and adapted to a bare of 10 patients¹²: (5) $$NNC=\left(treatmentcostusingdrugB*10\right)/\left(treatmentcostusingdrugA-treatmentcostusingdrugB\right)$$(5) where drug B’s cost is that of a rituximab biosimilar, and drug A’s cost is the highest cost option (reference rituximab).

Relative amount of Jordan Dinar (JOD) spent on rituximab options

Following Alkatib et al.²³, the relative amount of one JOD spent on each of the rituximab options versus the lowest cost rituximab option was estimated to present the value of one JOD in purchasing the rituximab options: (6) $$RelativeamountofJODspentonrituximaboption=treatmentcostofanytreatmentoption/treatmentcostofthelowestcostoption$$(6)

Results

Total annual cost to treat a hypothetical patient

Table 2 shows the total annual costs to treat a hypothetical patient. In the cost-saving and cost-wastage scenarios, Rixathon was associated with the lowest annual cost followed by Truxima, Tromax, and reference rituximab. Generally, in the cost-saving scenario, all rituximab options were associated with greater cost savings than in the cost-wastage scenario averaging JOD1,493 (23%). Notably, in both scenarios, one-year treatment of a previously untreated FL patient was associated with the highest cost among all indications and one-year treatment of a RA patient was associated with the lowest cost among all indications.

Table 2. Total annual cost to treat a hypothetical patient in JOD^a.

Treatment	Rixathon		Truxima		Tromax		Mabthera (reference)
Scenario	Cost-saving	Cost-wastage	Cost-saving	Cost-wastage	Cost-saving	Cost-wastage	Cost-saving	Cost-wastage
Previously untreated FL	4,380	5,637	6,174	8,651	6,516	8,760	16,830	23,709
RFL	4,015	5,167	5,660	7,930	5,973	8,030	13,147	21,733
DLBCL	2,920	3,758	4,116	5,767	4,344	5,840	11,220	15,806
CLL	2,840	2,818	3,857	4,326	4,148	4,380	10,488	11,855
RA	939	939	1,442	1,442	1,460	1,460	3,952	3,952
GPA & MPA	1,930	2,349	2,779	3,605	2,902	3,650	7,586	9,879
PV	1,174	1,174	1,802	1,802	1,825	1,825	4,939	4,939

Abbreviations. FL, Follicular Lymphoma; DLBCL, Diffuse Large B-Cell Lymphoma; CLL, Chronic Lymphocytic Leukemia; RA, Rheumatoid Arthritis; GPA & MPA, Granulomatosis with Polyangiitis AND Microscopic Polyangiitis; PV, Pemphigus Vulgaris, JOD: Jordanian Dinar.

^aThe costs calculated for a person with BSA = 1.783m² in Jordanian dinars (1 USD = 0.71 JOD).

Head-to-head comparisons

Table 3 shows the head-to-head annual cost comparisons. To note, in this table the differential estimates below the treatments’ names are for the cost-saving scenario, while the estimates above the treatments’ names are for the cost-wastage scenario. In the cost-saving scenario, the highest savings (JOD12,451) are achieved when reference rituximab is fully replaced with Rixathon in previously untreated FL. The lowest savings are associated with Truxima fully replacing Rixathon in all indications. On the other hand, in the cost-wastage scenario, the highest savings (JOD18,072) are achieved when Mabthera is fully replaced with Rixathon in the treatment of previously untreated FL. The lowest savings are associated with the use of Truxima instead of when Rixathon in all indications.

Table 3. Head-to-head comparisons for all indications in JOD^a.

Indication	Truxima		Tromax		Mabthera		Treatment
	Cost saving	Cost wastage	Cost saving	Cost wastage	Cost saving	Cost wastage
Previously untreated FL	1,794	3,014	2,136	3,123	12,451	18,072	Rixathon
	–	–	342	109	10,656	15,058	Truxima
	–	–	–	–	10,314	14,949	Tromax
RFL	1,645	2,763	1,958	2,863	9,133	16,566	Rixathon
	–	–	313	100	7,488	13,803	Truxima
	–	–	–	–	7,174	13,703	Tromax
DLBCL	1,196	2,010	1,424	2,082	8,300	12,048	Rixathon
	–	–	228	73	7,104	10,039	Truxima
	–	–	–	–	6,876	9,966	Tromax
CLL	1,017	1,507	1,308	1,562	7,648	9,036	Rixathon
	–	–	291	54	6,631	7,529	Truxima
	–	–	–	–	6,340	7,529	Tromax
GPA & MPA	849	1,256	972	1,301	5,656	7,530	Rixathon
	–	–	123	45	4,807	6,274	Truxima
	–	–	–	–	4,684	6,229	Tromax
RA	502	–	521	–	3,012	–	Rixathon
	–	–	18	–	2,510	–	Truxima
	–	–	–	–	2,492	–	Tromax
PV	628	–	651	–	3,765	–	Rixathon
	–	–	23	–	3,137	–	Truxima
	–	–	–	–	3,114	–	Tromax

Abbreviations. FL, Follicular Lymphoma; DLBCL, Diffuse Large B-Cell Lymphoma; CLL, Chronic Lymphocytic Leukemia; RA, Rheumatoid Arthritis; GPA & MPA, Granulomatosis with Polyangiitis AND Microscopic Polyangiitis; PV, Pemphigus Vulgaris.

^aJordanian Dinar (1 USD = 0.71 JOD).

Changes in patient access to rituximab

Table 4 shows the percent change in patient access across the various indications for the cost-saving scenario. These reflect the different dosing regimens and how minimizing wastage was associated with savings and expanded treatment access. In contrast, the percent change in patient access in the cost-wastage scenario did not differ across the studied indications, because wastage was similar in all indications.

Table 4. Changes in patients’ access to the treatment.

Indication	Truxima	Tromax	Mabthera	Treatment
Previously untreated FL	41%	49%	284%	Rixathon
	–	6%	173%	Truxima
	–	–	158%	Tromax
RFL	41%	49%	227%	Rixathon
	–	6%	132%	Truxima
	–	–	120%	Tromax
DLBCL	41%	49%	284%	Rixathon
	–	6%	173%	Truxima
	–	–	158%	Tromax
CLL	36%	46%	269%	Rixathon
	–	8%	172%	Truxima
	–	–	153%	Tromax
GPA & MPA	44%	50%	293%	Rixathon
	–	4%	173%	Truxima
	–	–	161%	Tromax
RA	53%	55%	321%	Rixathon
	–	1%	174%	Truxima
	–	–	171%	Tromax
PV	53%	55%	321%	Rixathon
	–	1%	174%	Truxima
	–	–	171%	Tromax
All indications in the cost wastage scenario	53%	55%	321%	Rixathon
	–	1%	174%	Truxima
	–	–	171%	Tromax

Abbreviations. FL, Follicular Lymphoma; DLBCL, Diffuse Large B-Cell Lymphoma; CLL, Chronic Lymphocytic Leukemia; RA, Rheumatoid Arthritis; GPA & MPA, Granulomatosis with Polyangiitis AND Microscopic Polyangiitis; PV, Pemphigus Vulgaris.

In the cost-saving scenario, at 321% the highest increase in patient access to rituximab was achieved when reference rituximab is fully replaced with Rixathon in the treatment of a PV or RA patient; followed by the GPA and MPA at 293%; previously untreated FL or DLBCL at 284%; and RFL at 227%. In the cost-wastage scenario, 321% was the highest increase in patient access to rituximab when reference rituximab is fully replaced by Rixathon in any of the studied indications.

Number-needed-to-convert (NNC) to the most cost-efficient drug

As shown in Table 5, in the cost-saving scenario, Rixathon was associated with the lowest NNC when switching from reference rituximab to provide an additional 10 patients with Rixathon treatment on a budget-neutral basis in all indications. The NNC was 4 for all indications, except for RFL where the NNC was 5 to increase access to 10 patients. The NNC was the highest when Tromax was replaced with reference rituximab. The NNC was 9 for RFL; 7 for previously untreated FL, DLBCL, CLL; and 6 in RA, GPA and MPA, and PV. In the cost-wastage scenario, Rixathon had an NNC of 4 in all indications, compared to 6 for Truxima and Tromax.

Table 5. NNC to gain additional access for 10 patients accessed to a rituximab biosimilar from Mabthera.

Indication	Rixathon	Truxima	Tromax
Cost-saving scenario
Previously untreated FL	4	6	7
RFL	5	8	9
DLBCL	4	6	7
CLL	4	6	7
RA	4	6	6
GPA & MPA	4	6	6
PV	4	6	6
Cost-wastage scenario
All indications	4	6	6

Abbreviations. FL, Follicular Lymphoma; DLBCL, Diffuse Large B-Cell Lymphoma; CLL, Chronic Lymphocytic Leukemia; RA, Rheumatoid Arthritis; GPA & MPA, Granulomatosis with Polyangiitis AND Microscopic Polyangiitis; PV, Pemphigus Vulgaris.

Relative amount of JOD spent on rituximab options

As Table 6 indicates, Rixathon was considered the reference option as it was associated with the lowest annual cost among all other rituximab options. In the cost-saving scenario, the amount spent on Truxima ranged between JOD1.41 to JOD1.53 compared to JOD1 spent on Rixathon; a range between JOD1.46 to JOD1.55 was spent on Tromax compared to JOD1 spent on Rixathon; and a range of JOD3.27 to JOD4.21 was spent on reference rituximab compared to JOD1 spent on Rixathon. In the cost-wastage scenario, for each JOD1 spent on Rixathon in the treatment of the six indications, JOD1.53 was spent on Truxima, JOD1.55 on Tromax, and JOD4.21 was spent on reference Rituximab.

Table 6. JOD amount spent relative to each 1 JOD spent on Rixathon.

Cost-saving scenario								Cost-wastage scenario
Treatments	Previously untreated FL	RFL	DLBCL	CLL	RA	GPA & MPA	PV	All indications
Truxima	1.41	1.41	1.41	1.36	1.53	1.44	1.53	1.53
Tromax	1.49	1.49	1.49	1.46	1.55	1.50	1.55	1.55
Mabthera	3.84	3.27	3.84	3.69	4.21	3.93	4.21	4.21

Abbreviations. FL, Follicular Lymphoma; DLBCL, Diffuse Large B-Cell Lymphoma; CLL, Chronic Lymphocytic Leukemia; RA, Rheumatoid Arthritis; GPA & MPA, Granulomatosis with Polyangiitis AND Microscopic Polyangiitis; PV, Pemphigus Vulgaris; JOD, Jordanian Dinar (1 USD = 0.71 JOD).

Discussion

This is the first cost-efficiency analysis and expanded access study that evaluates the adoption of rituximab biosimilars (Rixathon, Tromax and Truxima) in comparison to the reference rituximab (Mabthera) for Jordan public jurisdictions. This cost-efficiency analysis and expanded access study considered all six approved rituximab indications related to hematologic cancers and autoimmune diseases.

Rituximab treatments have been approved in Jordan to treat six indications. These treatments are purchased for the public health sector through a joint procurement process that considers tender prices and therefore not the prices listed by the JFDA for the public. In the case of this study, we used the tender prices paid by the JPD for the year 2022. This study aims to inform government decision-makers about the cost-efficiency of all available rituximab options in the Jordanian market, and how these savings are so considerable that they enable many more patients to be treated with rituximab across the variety of approved indications, without any additional budget implication for the Jordanian public health payer.

The implications of this study are fivefold. First, considering the cost-saving and cost-wastage scenarios, rituximab biosimilars showed cost savings over rituximab reference (Mabthera) in all the six approved indications (previously untreated FL, RFL, DLBCL, CLL, RA, GPA, MPA and PV). These savings can be allocated efficiently to increase patient access to rituximab treatment in the six indications.

Second, in the cost-wastage scenario, treating a case of previously untreated FL for one year was associated with the highest cost at JOD23,709 using reference Rituximab (Mabthera); and treating a case of RA for one year was associated with the lowest cost at JOD939 if this was with Rixathon. In the cost-saving scenario, while the reference rituximab was still associated with the highest yearly cost over all other options in the treatment of previously untreated FL, this cost was 29% lower than the cost-wastage scenario. However, once rituximab biosimilars were considered, the difference between the cost-saving and the cost-wastage scenario increased markedly across all indications. Hence, the cost-saving scenario is advocated in this study to minimize dose wastages.

Third, among all the included biosimilars, Rixathon was associated with the lowest yearly cost in the six indications, coupled with the highest number of patients with access to it when all the other rituximab biosimilars and reference rituximab were replaced with Rixathon. It is worth noting that the financial superiority of Rixathon over the other options in this study is limited to the perspective of the public sector payer, which considers the tender prices offered by rituximab suppliers to the JPD in Jordan. However, Rixathon was not the lowest-cost option from the perspective of the private sector. Selling prices for the private sector are provided in the supplementary material (Table S7).

Fourth, while the study compared the economic consequences of four rituximab options using tender prices, the reference rituximab price was less elastic compared with its biosimilars. The differences in tender prices between the biosimilars are minimal as shown in Table 1. The price of reference rituximab (Mabthera) was JOD987.88 and JOD414.65 for the 100 mg/10 ml and 500 mg/50 ml vials, respectively, which is 232.9% more than the most expensive biosimilar (Tromax) for the 100 mg/10 ml vial, and 270.6% more for the 500 mg/50 ml vial. This was reflected in this study in terms of changes in patient access to rituximab treatment. The increases in patient access among different biosimilars was not as pronounced compared with switching between reference rituximab and any other biosimilar.

Notably, in the cost-saving scenario, switching patients from reference rituximab to Rixathon, the lowest cost biosimilar, was associated with an increase in patient access ranging between 284% and 321%. While in the cost-wastage scenario, switching patients from reference rituximab to Rixathon, was associated with increased patient access by 321%. This is also reflected in the respective NNCs.

Fifth, the estimates of the relative amount of JOD spent on rituximab options is a novel contribution and assesses the economics of biosimilars from a different angle. Given that Jordan is a limited-resource country and budgets to treat costly diseases are reviewed critically, this study aimed to summarize the financial impact for decision-makers about rituximab options. Using the lowest-cost option, Rixathon as the benchmark, we estimated the incremental JOD fraction for each of the three biosimilar options. For each JOD1 spent on Rixathon, an additional JOD3.21 must be spent on the reference Mabthera, an additional JOD0.55 on Tromax, and an additional JOD0.53 on Truxima.

This study considered that all rituximab biosimilars are comparable to reference rituximab in terms of efficacy and effectiveness. This was based on regulatory practices in which biosimilars are evaluated mainly on the basis of equivalence trials. However, few manufacturers have tried to go the non-inferiority route to leave the door open to their product being a bio-better (reaching outside of what would have been the upper bound of the equivalence margin)²⁴. If this were to be found to be the case, the differential clinical benefit would warrant a comparative cost-effectiveness analysis. Moreover, as this study is the first cost-efficiency study conducted on rituximab options for Jordan public sector jurisdictions, similar findings in similar jurisdictions are not available yet. Low and middle-income countries may benefit from the design of this study to inform decision-makers on rituximab options.

The study has certain limitations that need to be considered in future studies. Because patient-level data are lacking in Jordan, the study simulated the treatment of a hypothetical patient. The study does not consider changes that might happen in future practice patterns, which could be driven by increased utilization and physicians’ adoption of biosimilars. The uptake of subcutaneous rituximab (Mabthera SC) in FL, CLL and DLBCL was not included in this study. This is because the clinical advantage of Mabthera SC over Mabthera IV is not confirmed yet.

Jordan and neighboring countries adopt reference-based pricing for pharmaceuticals. Adopting an innovative reference-based pricing mechanism integrated within a managed entry agreement hold the potential to encourage price reduction and increase patient access to biological treatments^25,26. Further, real-world research on the patterns of conversion to biosimilars and patients’ unmet needs could provide payers, providers, decision-makers, and patients more informative insights about the factors that influence the selection of rituximab biosimilars for a specific jurisdiction.

Conclusions

Overall, rituximab biosimilars were associated with cost savings in all approved indications in Jordan compared to the reference rituximab, specifically with the government tender prices for the year 2022. Rixathon was associated with the lowest annual cost, highest percentage of patient access for all six indications, and lowest NNC to gain 10 additional patients accessed to a rituximab treatment from reference rituximab.

Transparency

Author contributions

All authors met ICMJE and COPE criteria and contributed substantively to the study as follows: study concept, IA, LM, NA, HH; study design, HH, NA, IA; model development and simulations, HH; review and interpretation of results, HH, NA, IA, AA, MS, SH, OR, LM; Development of manuscript: HH, NA, IA, SH, OR; critical revisions to the manuscript: all authors.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Disclaimer

The contents of this manuscript are solely the authors’ views and may not be understood or quoted as being made on behalf of reflecting the position of the Saudi Food and Drug Authority.

Acknowledgements

None reported.

Declaration of funding

The work reported herein was performed without sponsorship or grant funding.

Declaration of financial/other relationships

The authors report there are no competing interests to declare.

Data availability statement

The raw data that support the findings of this study are available from the corresponding author, upon reasonable request.

Notes

i Mabthera is a registered trademark of Roche Diagnostics GmbH, Mannheim, Germany.

ii Truxima is a registered trademark of Hikma, Amman, Jordan.

iii Rixathon is a registered trademark of Novartis, Basel, Switzerland.

iv Tromax is a registered trademark of MS Pharma, Amman, Jordan.