A comparison of anti-IL-17A, anti-TNF, and anti-IL-12/23 biologics for moderate-to-severe plaque psoriasis in India, based on cost per NNT and its effect on the therapeutic landscape and outcome

Introduction

Psoriasis is a chronic, inflammatory, immune-mediated skin disease, particularly affecting people with a strong genetic predisposition.¹ The WHO recognises it as a chronic, painful, disfiguring, and disabling disease without a cure.² Its prevalence in India ranges from 0.44 to 2.8%.³ The prevalence may vary regionally based on environmental and genetic factors.⁴ According to the global psoriasis atlas (GPA) data, it is estimated that 2.9 million (0.8 to 10.0 million) people in India are affected by psoriasis.⁵ Plaque psoriasis (PsO) is the most common phenotype of psoriasis (seen in 80% of patients).^6,7 Histologically, the lesions show epidermal hyperplasia and dermal infiltration of immune cells. The prevalent view is that IL-23/IL-17 is the key pathogenic axis that drives psoriasis. Multiple biologics targeting TNF-α, IL-23, and IL-17 have shown remarkable outcomes in the treatment of psoriasis.⁸

PsO has a significant negative effect on the patient’s quality of life (QoL).⁹ A study from India reported that 64% of patients with moderate-to-severe PsO reported its negative impact on their lives. Around 31% of patients reported that it reduced their productivity, 28% faced unemployment at some stage, and 27% could not attend work-related social events and were assigned tasks requiring fewer social interactions. Almost 27% reported social stigma, and 23% of patients felt socially left out.¹⁰ Psoriasis can also lead to high self-consciousness and low self-esteem among patients because it is still considered a contagious disease in society.¹¹ The disease is often associated with cardiovascular and other non-communicable diseases (NCDs) and psychological distress.⁹ It is also associated with a significant financial burden due to the prolonged and high cost of therapy.¹² Effective skin clearance is important for improving the QoL of patients with PsO.^13-15

The introduction of biologics for the management of PsO has led to a significant change in the treatment paradigms of moderate-to-severe PsO. Usage of new-generation biologics in PsO has shown rapid clearance of cutaneous lesions resulting in a 75%, 90%, and 100% improvement in psoriasis area and severity index (PASI75/90/100) in a high proportion of patients, and a substantial improvement in Dermatology Life Quality Index (DLQI) compared with conventional treatment modalities.^6,8,11,16 An added advantage is reduced target organ damage compared with conventional systemic therapy.¹⁶

Despite their clear benefits, biologics are not widely used in Indian patients, due to their high cost.³ Since India is largely a self-pay market, a group of experts recommended changes and adaptations regarding the dose and duration of biologics for PsO. Nevertheless, the final consensus stated that for the best possible benefits, the doses of these drugs should be taken in line with the drug label.³ A recent survey on the treatment of psoriasis among Indian dermatologists found that 70% used biologics in <2 cases per month, 26% used them in 2-5 cases, and only 4% used them in >5 cases per month. The average duration of biologic use was only 3-6 months by 40% of dermatologists and 6-12 months by 27%. The major reasons for discontinuation of biologics were achievement of remission (50%), cost (24%), inadequate response (15%), and adverse effects (11%). Notably, 88% of respondents admitted that eliminating the cost barrier would increase their use of biologics.¹⁶ In another study, 56% of dermatologists considered the high cost of therapy as the primary reason for non-compliance.¹⁰ An additional challenge in India is the lack of patient awareness about biologics. A recent survey found that only 19% of patients with psoriasis were aware of biologics as a treatment option. Patients who used biologics were more satisfied (67%) than non-users (57%), and 72% of patients using biologics expressed maximum satisfaction with skin clearance results.¹⁰ However, only one-third of patients reported compliance with their current therapy.

It is difficult for an Indian dermatologist to prescribe biologics for PsO despite their superior efficacy, due to the high costs.⁹ To aid clinicians in decision-making, a tool comparing the efficacy of therapeutic options vis-a-vis their cost could be very useful. When comparing the efficacy of therapies, randomised controlled trials (RCTs) are considered the highest level of evidence due to a lower risk of bias and systematic errors.¹⁷ However, there are no RCTs comparing the efficacy of all biologics available for treating PsO; hence, network meta-analysis (NMA) is often used for these comparisons. NMA is an established statistical method to generate efficacy estimates comparing a range of drugs, combining direct and indirect evidence, which can be expressed as a Number Needed to Treat (NNT).¹⁸ The use of NNT as a measure of effect for RCTs is recommended by the Consolidated Standards of Reporting Trials (CONSORT).¹⁹ NNTs can be combined with treatment cost, providing cost per NNT information, which offers useful insights into the relative efficacy and cost of different therapies.²⁰

The objective of this study was to determine the relative efficacy (based on PASI 90 and 100) and cost of biological therapies approved/available in India for the treatment of moderate-to-severe PsO based on the cost per NNT.

Methods

The biologics considered for this study include IL-17A antagonists (ixekizumab, secukinumab), TNFi (adalimumab, etanercept, infliximab), and anti-IL-12/23 (Ustekinumab). The time points considered for the analysis were 12 (induction therapy), 24, 52 (1 year), and 104 weeks (2 years) after initiation of therapy. The number of doses considered for each drug up to these time points was based on the approved dosing schedules [Table 1].^21-25 Although the induction phase can vary between different biologics, 12 weeks was considered the standard induction phase in this analysis, as this is a time point for which NNTs of various therapies were available.

Calculation of the cost of biologic per NNT

By multiplying the NNT of a drug with the corresponding treatment cost, the MRP per NNT of each biologic was obtained.²⁹ This was done for PASI100 and 90 responses at the end of 12, 24, 52, and 104 weeks.

The NNTs for 24 weeks were assumed to be the same as those for the 12-16 weeks period. The NNTs for 104 weeks were assumed to be the same as those for 44-52 weeks. This was because the NNTs for these time points were not available in the published NMA.

Costs for monitoring or treating patients for adverse events during treatment, as well as the cost of administration of therapy, were not included in the calculation.

The cumulative cost from week 0-104 was calculated for the cost of the biologic and cost per NNT of the Biologic for PASI 90 and PASI 100 by adding years 1 (week 0 to 52) and 2 (week 53 to 104), respectively.

Results

Cost of biologics at MRP

The cost of treatment for each drug at MRP has been shown in Figure 1 and Supplementary Table 1. Ustekinumab is the most economical option at all time periods based on the MRP.

Supplementary Table 1

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Figure 1:

Biologic cost per patient at MRP.

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Cost of biologics per NNT for PASI100 response

Ixekizumab had the lowest NNT amongst all biologics [Figure 2 & 3] and [Supplementary Table 2] for PASI 100 for both short and long term. The cost per NNT for a PASI100 response was lowest for ixekizumab at all time points, followed by ustekinumab. Up to 12 weeks, the cost difference between ixekizumab and ustekinumab was 14% in favour of ixekizumab. The difference in the cost per NNT between ixekizumab and ustekinumab was 24.4% at 24 weeks, 12% at year 1, and 3.7% at year 2, in favour of ixekizumab. The cost per NNT for etanercept was highest at all time points. The cumulative cost per NNT for PASI 100 for 2 years was lowest for ixekizumab, followed by Ustekinumab, and the difference was 9% in favour of ixekizumab.

Supplementary Table 2

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Figure 2:

Biologic cost per NNT for PASI100 response at MRPs at short term.

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Figure 3:

Biologic cost per NNT for PASI100 response at MRPs at long term.

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Discussion

With the approval of newer biologics, the number of treatment options for the management of PsO in India has increased.³ Hence, it is imperative for dermatologists to be aware of the comparative efficacy and treatment costs when prescribing these agents.

Our study showed that ixekizumab has the lowest cost per NNT for PASI 100 response at all time points, irrespective of the MRP. Nevertheless, if the cost per NNT(PASI100) was considered for the total duration of treatment, ixekizumab had the lowest cost if the patient continued treatment for >12 weeks and <2 years. Ustekinumab was the most economical option for a PASI90 response at MRP, followed by ixekizumab. The lowest cost per NNT of ixekizumab for all time points for PASI100 response can be attributed to the lowest NNT of ixekizumab among the compared biologics, indicating the higher efficacy of ixekizumab compared to the other biologics.²⁶

PASI is one of the most used outcome measures for PsO. It combines qualitative (presence of erythema, infiltration, and desquamation) and quantitative parameters (proportion of affected area for each body region).³⁰ The PASI score can range from 0 (no lesions) to 72 (disease at highest degree). A decrease in PASI score from the initial value is used to evaluate the response to treatment as an improvement of at least 75% (PASI75), 90% (PASI90), or 100% (PASI100), respectively.³⁰ We calculated the cost per NNT for PASI90 and PASI100 outcomes because a PASI90 response or higher has a significantly higher impact on Dermatology Life Quality Index (DLQI) improvement. PASI90 is associated with a significantly higher proportion of patients achieving a DLQI of 0–1. A DLQI of 0-1 indicates that the disease has no effect on the patient’s health-related Quality of Life (QoL).³¹ Hence, it has been suggested that a PASI 90 response or higher should be considered the most relevant treatment objective for PsO.^31-33 Incremental PASI improvements correspond with increasing benefits in Health-Related Quality of Life (HRQoL) and less perceived symptoms. Complete skin clearance offers the greatest benefits in HRQoL and patient-perceived symptoms, surpassing skin clearance between 90% and 100%. Hence, PASI 100 should be the goal of treatment for patients with PsO.³⁴

Similar to our study, others have also demonstrated the superior performance of ixekizumab compared to other biologics approved for PsO, in terms of cost per NNT for PASI 100 and PASI 90 responses, across various markets outside India.^{6,20,29,26,35} As treatment goals for moderate-to-severe PsO aim to achieve the highest possible levels of clearance, costs per NNT favour the biologics with higher efficacy, such as ixekizumab.³⁶

While it seems that the economic biological at a discounted price is adalimumab, here it must be understood that it is pertinent to examine the relative efficacy of biologicals based on existing evidence.⁸ In both the short (10–16 weeks) and long (44–60 weeks) term, risankizumab had the highest PASI 90 scores (71.6% and 79.4%, respectively) when compared to other oral and injectable biologics. This was followed in the short term by PASI90 by brodalumab (70.8%), ixekizumab (70.6%), and guselkumab (67.3%), while long-term PASI 90 rates were next highest with guselkumab (76.5%), brodalumab (74%), and ixekizumab (73.9%).³⁷ Based on existing data, ixekizumab appears to be a suitable biologic among those available in India and aligns with our findings.

Limitations

There are some limitations associated with our study. We used the NNT values from a previously published NMA. Another limitation is that cost-per-NNT analyses are inherently based on RCT evidence and thus cannot account for any real-world factors that may further impact the true cost of therapy, such as compliance. Further, the costs of lab investigations and visits to the clinic for adverse event monitoring were not considered in our analysis. However, these costs do not vary significantly between various biologics. A third limitation is the extrapolation of NNT values from 12-16 weeks to 24 weeks and from 44-52 weeks to 104 weeks. However, there is no published literature for NNT values at 24 and 104 weeks. The fourth limitation is that we have not considered the cost per NNT for ustekinumab for adults weighing >100 kg. The fifth limitation is not to consider the administration cost in the analysis, as infliximab is administered intravenously and thus could have a higher administration cost compared to other drugs, which are administered subcutaneously. A final limitation is that the cost of biologics is variable and subject to fluctuation in the market due to changes in prices of the brands and availability of biosimilars.

The implications in conjunction with a large body of evidence show that while a short-term cost benefit would favour adalimumab, ixekizumab and ustekinumab would be the favoured biologics in terms of cost per NNT for PASI 100 and PASI 90, respectively. Guselkumab has been recently launched but is not approved for Psoriasis in India so was not analysed. This has significant value for the public health system, where biologics are administered to patients, allowing costs and efficacy to be considered in terms of both short- and long-term goals.

Conclusion

This cost-impact shows that among the approved biologics for the treatment of moderate-to-severe PsO in India, ixekizumab has the lowest cost per NNT for a PASI100 response for induction and maintenance therapy up to 2 years. Our analysis at the prices listed at present, indicates that ixekizumab seems to have the highest relative efficacy based on cost per NNT amongst the approved biologics in India, though cost dynamics and generics may change the analysis over time. This data can be used both by public health agencies and dermatologists to estimate the cost to the patient on a short- and long-term basis, considering the efficacy, price while choosing advanced therapies.