Psoriatic arthritis (PsA) is a chronic, progressive inflammatory disease characterized by skin and musculoskeletal manifestations.1 PsA can cause permanent joint damage, which can be very debilitating for patients, and is associated with a significant economic burden.2,3

The main treatment goal for patients with PsA is to maximize health-related quality of life through control of inflammation, symptoms, prevention of structural damage, normalization of physical function and social participation.4–7 The European League Against Rheumatism (EULAR)4,5 recommends conventional disease-modifying drugs (DMARDs) (methotrexate, leflunomide, sulfasalazine) as first-line treatment for PsA. For patients with an inadequate response or those in whom conventional treatment has failed, biologic treatments that act as tumour necrosis factor inhibitors (TNFi), such as adalimumab, certolizumab pegol, etanercept, golimumab and infliximab, are recommended, to be followed by inhibitors of interleukin (IL) 12, 23 and 17, such as ustekinumab (IL12/23i) and secukinumab (IL17i). For its part, the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA)6,7 recommends phosphodiesterase 4 inhibitor (PDE4i) apremilast or biologic treatments (TNFi, IL12/23i, IL17i) in peripheral PsA patients in whom DMARD treatment has been unsuccessful. Regarding the Spanish Society of Rheumatology (SER)8 recommends the use of biologic treatments for patients with peripheral PsA refractory to at least one DMARD without prioritization among biologic treatments, leaving the choice to the physician. Furthermore, it recommends that patients who fail to TNFi switch to another biologic treatment (TNFi) or a different mechanism of action, such as IL12/23i, IL17i or targeted DMARD (PDE4i) when this reveals most appropriate than a biologic treatment due to the patient profile (Grade of recommendation B).8 According to the SER, the choice of any available biologic treatment would be a valid option in most cases. Nevertheless, up to now, only one head-to-head study comparing biologics used to treat PsA has been published,9 which makes comparisons difficult and, by extension, decision-making in clinical practice. The results of a recently published network meta-analysis found that secukinumab was the most efficacious and safest treatment for PsA among all IL-inhibitor biologics.10 However, there are two recent matching adjusted indirect comparison studies (MAIC) analysing differences between secukinumab and adalimumab for treating PsA11,12 and reporting discordant results. When selecting a given drug to treat PsA, consideration should be given both to the features of the disease (clinical phenotype, severity, poor prognostic factors) as well as to those of the molecule itself (evidence, experience, efficacy, safety, optimization) and, in cases where it is not possible to establish differences based on the available scientific evidence, the economic data, as they provide information for decision making.8

The choice between biologic treatment with adalimumab or with secukinumab is of special interest because of the number of elements that inform decision-making from the clinical as well as the economic point of view that are present in both. Based on current available scientific evidence13 and existing guidelines,4–8 the options of initiating biologic treatment with secukinumab and, in the event of inadequate response, to intensify the dose, or initiating treatment with adalimumab and, in the event of treatment failure, to switch to secukinumab are both equally viable. Moreover, when it comes to determining which of the two options would be most efficient, the recent appearance on the market of drugs that are biologically similar to adalimumab at lower prices than the original biologic drug plays an important role, as it is a factor that may add additional uncertainty to decision-making.

In this context, we sought to conduct a cost-consequence study to help make decision-making about treatment for patients with PsA easier, through an analysis of the efficiency of secukinumab and adalimumab as first biologic treatments.

A cost-consequence analysis was conducted using an Excel spreadsheet to assess the cost of pharmacological treatment with respect to clinical response of two possible treatment strategies for PsA, with a time horizon of 2 years, from the perspective of the Spanish National Health System (SNHS).

The analysis was based on a hypothetical cohort of 10 patients with PsA who initiated biologic treatment with secukinumab 150mg (cohort A) or adalimumab 40mg (cohort B) (Fig. 1). Patients in both cohorts who achieved clinical responses defined as the proportion of patients achieving improvement equal to or greater than 20%, 50% and 70% in the American College of Rheumatology (ACR 20/50/70) response criteria at week 24 of treatment would continue the initial treatment with secukinumab 150mg or adalimumab 40mg, respectively, while patients with inadequate response would receive secukinumab 300mg. In order to simplify the analysis, it has been assumed that all patients respond after week 24, without regard to other potential subsequent treatment failures.

Fig. 1.

Analysis scheme.

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Efficacy of the treatments

Data on clinical response to treatment at week 24 (ACR 20, ACR 50 and ACR 70) were extracted from the two matching-adjusted indirect comparison studies of secukinumab and adalimumab11,12 (Table 1). Although both publications compare the same treatments, different methodologies were used and the data used to determine effectiveness were from different clinical trials, so a priori, discordant results are to be expected. While Nash P. et al.11 found that response rates were numerically and statistically higher for secukinumab compared to adalimumab, Strand V. et al.12 found that, although response rates were numerically higher for adalimumab compared to secukinumab, these differences were not statistically significant. Given the discrepancies between both sources with respect to their methodologies and, consequently, their results, the data from the two available articles was analyzed separately. This way, it was possible to assess and compare the results from both perspectives and there was no loss of information that could be useful for decision-making, since these are the only comparative studies between both treatments for PsA.

Table 1.

Clinical efficacy data (at 24 weeks) used in the analysis: matching-adjusted indirect comparisons of secukinumab and adalimumab.

	Nash P. et al.10,a			Strand V. et al.11,b
Week 24	Secukinumab	Adalimumab	p-Value	Secukinumab	Adalimumab	p-Value
ACR 20	81.0%	57.0%	0.001	33.7%	43.2%	n.s.
ACR 50	58.6%	39.1%	0.019	27.5%	30.5%	n.s.
ACR 70	37.0%	23.2%	n.s.	17.9%	23.9%	n.s.

a

MAIC of the FUTURE 2 and ADEPT clinical trials.

b

MAIC of the FUTURE 1, FUTURE 2 and ADEPT clinical trials.

n.s.: not significant (p>0.05).

The main difference in methodology between the two articles is centred on the clinical trials selected for the comparisons. Whereas Nash P. et al.11 looked at the pivotal FUTURE 2 (secukinumab 150mg versus placebo) and ADEPT (adalimumab 40mg versus placebo) trials, Strand V. et al.12 also included the pivotal FUTURE 1 trial (secukinumab 150mg versus placebo). The reason Nash P. et al.11 gave for excluding the FUTURE 1 study was the fact that the dose of secukinumab that was administered was not the one approved on the summary of product characteristics (SmPC)13 and that the induction phase consisted of a 10mg/kg intravenous dose at weeks 0, 2 and 4. Strand V. et al.12 were aware of this limitation, so they performed a sensitivity analysis that did not include the FUTURE 1 study. Although they indicate that the efficacy of ACR 20 and ACR 50 responses of adalimumab compared to secukinumab were 6.4% lower and 5.9% lower, respectively, while the ACR 70 response was 0.6% higher (no statistically significant differences) authors did not provide detailed results thus these data has not been included in our analysis.

This data was used to determine the number of patients in each cohort with a clinical response (ACR 20/50/70) at 24 weeks. For example (Fig. 2), using the ACR 20 results reported in the Nash P. et al.11 analysis, we can see how 10 patients in cohort A start out by receiving treatment with secukinumab at a dose of 150mg and that at 24 weeks, 8 (81.0%)11 continue receiving the same treatment until the end of the time horizon while the dose administered to the other 2 (19%) would be increased (secukinumab 300mg). With respect to cohort B, of the initial 10 patients, 6 would continue to receive adalimumab 40mg until the end of the time horizon while the other 4 would switch to secukinumab 300mg. We proceeded in the same way with regard to the study conducted by Strand V. et al.12 (Fig. 2).

Fig. 2.

Basis for estimating the number of patients in each cohort who responded to treatment at 24 weeks.

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Pharmacoeconomics allows treatment options to be prioritized by taking into account both the health benefits and the economic impact of their use. This paper provides additional information to help decision-making before initiating biologic treatment for patients with PsA, showing the clinical and economic importance of making the appropriate choice with regard to the first line of therapy for a chronic disease that requires prolonged treatment and may result in a gradual ‘exhaustion’ of therapeutic alternatives.

The main results show that secukinumab is more efficient as first-line biologic treatment for patients with PsA compared to initiating treatment with adalimumab. The results obtained are sustained at every level of clinical response (ACR 20, 50 and 70) that was analyzed and by the two matching-adjusted indirect comparison studies of secukinumab and adalimumab that are published at present and were used as sources of scientific evidence.10,11 In particular, with regard to the results obtained for the efficacy outcomes ACR 50/70, which are those most often considered when assessing clinical response in routine clinical practice, the cost for cohort A was 28%/23% (Nash P. et al.10) and 18%/16% (Strand V. et al.11) lower than for cohort B.

Also, the sensitivity analysis performed allowed us to establish the threshold of the discount rate on the notified ex-factory price of adalimumab that would cause results to vary and make secukinumab less efficient than adalimumab. In this regard, we found that the notified ex-factory price of adalimumab would have to be at least 65%/75% lower than the current price for the least expensive biosimilar drug when we used the ACR 50/70 outcomes reported by Nash P. et al.10 and at least 40%/50% lower when we used the ACR 50/70 outcomes reported by Strand V. et al.,11 reflecting that the efficacy of secukinumab for the treatment of PsA weighs more heavily than the cost when comparing its efficiency to that of adalimumab. If the cost of secukinumab were to decrease, these percentages would no longer be valid and would have to be recalculated, since the discount on the price of adalimumab would have to be even greater.

These findings are based on the available evidence and are consistent with recent recommendations by the SER.8 On the one hand, the available evidence suggests that the response to treatment of biologic-naive patients will be superior to that of patients who have previously failed an TNFi, so the hoped-for efficacy will always be better the sooner a biologic drug is used, regardless of which one. On another hand, we have demonstrated that initiating treatment with secukinumab 150mg and increasing the dose in the event of inadequate response is less costly than initiating treatment with adalimumab 40mg and then switching to secukinumab after failure. The flexibility in the choice of the dose provided by secukinumab, by starting at 150mg in treatment-naive patients with the possibility of increasing to a dose of 300mg if there is a lack of primary response, is considered a big advantage when it comes to achieving efficiency in treatment. Since a priori higher costs are expected, given the induction phase that is required when secukinumab is initiated, whether for biologic-naive patients receiving secukinumab 150mg or for patients who have had an inadequate response to an TNFi and switch to secukinumab 300mg, using it sooner in naïve patients provides benefits in efficiency in terms of cost of treatment and in efficacy in terms of clinical response, and therefore costs avoided with respect to using it after adalimumab failure.

This analysis has some limitations. Firstly, since no published clinical trial at the time of the analysis has directly compared secukinumab and adalimumab in PsA patients, this study relied on two available matching-adjusted indirect comparison studies. With regard to the specific sequences that were analyzed, although recent recommendations for the treatment of PsA8 include switching to another biologic treatment (IL12/23i or IL17i or a targeted DMARD (apremilast)) after TNFi failure, the only indirect comparisons that have been published are for the two drugs we analyze here. Also, we did not consider switching from secukinumab to adalimumab, as there is no evidence to support its use after the failure of IL17i. Secondly, we did not analyze the clinical response of patients whose dose was increased or who switched treatments at week 24. Nevertheless, the analysis structure responds to the study's objective of assessing the efficiency of two possible options for initiating biologic treatment and this allowed us to simplify the analysis and obtain results for that change, whereas if we had included possible benefits of the subsequent therapy, it could have masked the results that were the objective of the study. Finally, a potential limitation may be the use of the notified ex-factory prices in the analysis, as it is usually somewhat higher than the final cost of drugs incurred by SNHS hospitals.

Despite the limitations identified above, the results of this cost-consequence analysis offer valuable information for decision-making and highlight the importance of making an appropriate choice of the first biologic treatment option for patients with PsA, since it may prove decisive both for clinical outcomes as well as for potential subsequent alternatives and economic impact on the health system. In any event, this analysis seeks to support health professionals in real-life situations who must make decisions about the choice of certain treatments based on the available scientific evidence and incorporating efficiency as another criterion. Future research may shed more light and provide for further analysis. Decision-making should be based on evidence and updated as knowledge increases. In this sense, this cost-consequences analysis based on matching-adjusted indirect comparison studies shows that the choice of secukinumab as first biologic treatment for patients with PsA may be considered a more efficient option with respect to adalimumab from the perspective of the SNHS.

This work was supported by Novartis Farmacéutica, S.A.