While therapeutic innovation is progressing rapidly, it often has substantial economic impacts on the Spanish health system.1 The incorporation and regulation of new drugs is a complex process that should ensure patient access to them while maintaining the economic sustainability of the health system in Spain.2 Furthermore, since drug efficacy is based on evidence obtained from clinical trials, the aforementioned health system is at risk of incorporating new drugs that may be ineffective in clinical practice or non-superior to those already available.2,3 Consequently, data derived from real-world clinical practice play a pivotal role in effectively addressing the uncertainty arising in this context.

Several financial instruments are available to mitigate this significant uncertainty, and among them, risk-sharing agreements (RSAs) are some of the most relevant. These agreements are established between drug providers and payers with the aim of linking the drug's price to a set of variables associated with outcomes.4

There are several types of RSAs, with performance-based RSAs commanding great interest.4,5 In these agreements, drug providers negotiate reimbursement with payers in the event of failure to achieve the expected clinical outcomes.5 These agreements are usually encountered in therapeutic areas with multiple treatment options and well-defined outcomes,5 such as cancer, infectious diseases, rare conditions, and autoimmune diseases.6,7 Regarding the latter group, biologic therapy has been positioned as an appropriate strategy for their management.8 However, the high cost and lack of real-world clinical experience with recently approved biologics necessitate the implementation of mechanisms that enable access while concurrently evaluating their use through evidence-based practice.9,10

Specifically, in the treatment of moderate-to-severe plaque psoriasis (msPs), the use of biologics and their biosimilars has broadened the therapeutic options.10,11 In total, 2.3% of the Spanish population is affected by msPs,12 a chronic immune-mediated inflammatory disease for which there is no curative treatment.13 When traditional topical and systemic treatments are ineffective or unsafe, several biological alternatives are available.11,13 In this setting, 2 categories of biologic agents are currently available, which can be classified based on their mechanism of action: tumour necrosis factor-α inhibitors (anti-TNF-α) and interleukin inhibitors.

The Psoriasis Area and Severity Index (PASI) is the standard tool for assessing the severity of skin involvement before and during treatment with these drugs.14 In most clinical trials with biologic therapies, the relative PASI score serves as the primary endpoint. The specific target is PASI 75, representing a 75% reduction in the PASI score from baseline; however, in routine clinical practice, the absolute PASI score is the more commonly used measure of effectiveness.15

In Spain, certolizumab pegol (CZP) is one of the approved biologic agents for treating msPs in adults eligible for systemic treatment. This anti-TNF-α agent was approved in Spain in 2018, and is dispensed under the trade name Cimzia.16 This agent has exhibited high efficacy in clinical trials, with 67%–83% of patients achieving PASI 75 at 16 weeks17–19; however, few studies have evaluated its effectiveness in real-world clinical practice, and are limited by the small size of the study sample.20,21

In 2020, an RSA was established between the pharmaceutical laboratory responsible for its commercialisation and 10 Spanish hospitals to facilitate its acquisition and dispensation in adult patients with msPs. These agreements set the absolute PASI score at 16 weeks as an objective outcome measure. This study contributes new evidence in real-world clinical practice of the effectiveness of CZP in adult patients with msPs, as well as by subgroup, within the framework of the agreement. We also investigate the effectiveness of CZP by using other scales commonly used for therapeutic decision-making in patients with msPs.

The implementation of an RSA for the treatment of msPs with CZP could mitigate the uncertainties associated with drug effectiveness, safety, and costs in real-world clinical practice.24 The results show that about 91% of patients met the RSA clinical target, in alignment with the current recommendations of the Psoriasis Group of the Spanish Academy of Dermatology and Venereology.9 The pharmaceutical laboratory reimbursed the hospitals for patients who did not reach the RSA clinical target, thus reducing the cost of treatment.

In Spain, manufacturers and hospitals commonly agree RSAs—especially those based on economic negotiations—and regions such as Catalonia have implemented outcomes-based RSAs25; nevertheless, there is little published evidence on such agreements in Spain.

To our knowledge, this is the first study on an outcomes-based RSA targeting psoriasis. Previous studies have explored the impact of this type of agreement in other diseases. In 2011, an RSA on the use of gefitinib for treating of non-small-cell lung cancer was implemented in the Spanish region of Catalonia. Although its efficacy has not been proven in clinical trials in the Spanish population, the results showed an association between the RSA and adequate effectiveness in real clinical practice, leading to direct and indirect benefits. In 2012, a risk-sharing program was implemented in a referral hospital for enzyme replacement therapy for lysosomal storage diseases.27 There were no cost savings because complete effectiveness was achieved in all patients, suggesting that the use of outcome-based RSAs should not only be based on economic aspects, but also on mitigating uncertainty regarding treatment effectiveness, especially in cases of rare diseases. In 2013, an RSA on the treatment of rheumatoid arthritis with CZP24 was established in Catalonia, and subsequently in other Autonomous Communities.28 The results showed cost savings for the pharmacy service and a reduction in the uncertainty associated with the actual efficacy of the drug. The results of our study are in line with these results, demonstrating that this type of RSA is an effective tool for improving efficiency within the healthcare system.

Regarding the clinical outcomes achieved in our study, there was an 8-point reduction in the absolute PASI score at follow-up, which was similar in the subgroups studied: men (6.3) vs. women (8.4) and biologic naïve patients (8.0) vs. non-naïve patients (7.4). Although the size of our sample was not comparable to that of the CZP clinical trials, our results are in line with those of the CIMPASI-1 and CIMPASI-218 clinical trials, confirming the efficacy and safety of the drug in routine clinical practice. Furthermore, the results of our study are also in line with those obtained in previous real-world studies.20,29–32 Carubbi et al. analysed 12 patients treated with CZP for psoriasis and psoriatic arthritis, finding a decrease in the absolute PASI score from 7.93 at the baseline visit to 0.29 at the end of follow-up.32 Vender et al. studied a total of 62 patients, observing a decrease in absolute PASI score from 13.0 points at baseline to 2.3 at follow-up.31 The results of our study were similar to those of Turkmen et al.,30 Vender et al.,31 and Carubbi et al.32 These studies found similar effectiveness between biologic naïve and non-naïve patients, suggesting that CZP is efficacious in patients with psoriasis regardless of their previous exposure to the biologic; however, these studies did not differentiate between men and women regarding its effectiveness. In women of childbearing age, CZP is an optimal drug of choice as well as the recommended drug because it is the only anti-TNF agent that does not cross the placenta during pregnancy, nor is it transferred through breast milk in lactation.33 Our study shows an improvement in effectiveness on all the scales used. In addition, the results obtained for men were also relevant, showing effectiveness in this group of patients.

Although the PASI is considered the gold-standard to evaluate effectiveness in psoriasis, other scales, such as the DLQI, BSA, and PGA, are relevant in therapeutic decision-making when treating patients with msPs with biologics, as they can be used to assess the impact of the disease on the patients' quality of life.13

Our study shows improvements on all the other scales used in relation to their baseline scores. In particular, we highlight the reduction in DLQI scores, given the impact of psoriasis on patients' quality of life. Of the studies cited, only those by Carubbi et al. and the CIMPASI-1 and CIMPASI-2 clinical trials used the DLQI; all these reported improvements of around 10 points, close to the 9-point improvement found in our sample. A DLQI score of 0/1 indicates no deterioration in health-related quality of life (HRQoL),34 whereas a decrease of ≥4 points is considered clinically significant35; thus, CZP had a beneficial impact on patients' HRQoL. We found a significant positive correlation between the DLQI and the PASI, which highlights the relevance of measuring HRQoL during treatment evaluation.

It is noteworthy that only 2 of the 6 patients who did not reach the RSA target discontinued treatment. The remaining 4 patients continued their treatment, possibly because they had shown a favourable response to the treatment they were receiving. In most of these patients, the results show that scores on the other scales were stable or improved during follow-up, indicating a clinically adequate response to treatment.

This study has several limitations. It is a retrospective study and relied on RSA data, with the PASI score as the primary outcome variable; thus, complete data were not obtained for the rest of the scales for the total sample. However, they were analysed in a large number of patients, thus complementing the treatment effectiveness data. The study is also limited by its sample size. The optimal sample size was not reached, likely due to the availability of multiple therapeutic alternatives for these patients and that in clinical practice they are mainly used in women of childbearing age. Furthermore, the sample size was insufficient to yield statistically significant results. Thus, larger sample sizes are needed validate the outcomes observed in real-world practice.

In conclusion, the female and male patients, and biologic naïve and non-naïve patients, who received CZP in real-world clinical practice experienced improvements in their PASI and DLQI scores of 80.6% and 66.4%, respectively, compared to their baseline scores. In addition, 90.9% of the sample achieved the target clinical response established in the RSA. The results show that the implementation of this type of agreement can generate direct or indirect benefits for all the agents involved in the process, as well as providing valuable information for decision-making.

In line with the results of clinical trials, the study shows that CZP is effective in the treatment of moderate–severe psoriasis.

The real-world results of this study show that the uncertainties associated with the use of CZP can be mitigated via the implementation of a risk-sharing agreement.

All the authors contributed substantially to study conception and design, data analysis and interpretation, and writing the article. All authors read and approved this version of the manuscript. Specifically, Andrés Navarro Ruiz and Fernando Toledo Alberola contributed to study design, data interpretation, and approval of the final version; Susana Aceituno contributed to data analysis and drafting the article; and the Arcoderm Group contributed to data collection and interpretation of the results.

None declared.

The study was approved by the Clinical Research Ethics Committee of the Hospital General Universitario de Elche, Spain (approved: 7 October 2021; code 12/2021).

Partial or preliminary results have been reported in the following congresses:

- XL + 1 Jornadas de Economía de la Salud (Zaragoza, Spain, 15–17 June 2022).

- 8th Psoriasis Congress (Madrid, Spain, 20–21 January 2023).