Assessing the value contribution of bimekizumab for the treatment of moderate-to-severe psoriasis using a multidisciplinary reflective multi-criteria decision analysis

Figures & data

Table 1. MCDA framework for the evaluation of drugs in moderate-to-severe psoriasis.

Domains/criteria	Type	Adaptations made on the EVIDEM framework (10th edition)
Need for the intervention		One criterion was disaggregated: The criterion effectiveness was disaggregated into three (level, rapidity and persistence of clearance), to capture relevant features in the assessment of drugs for moderate-to-severe psoriasis. One criterion was added: The criterion consistency of the effect was added, in order to capture outcomes from the use of the drugs in patients with psoriasis in specific locations (i.e. scalp, palmoplantar, etc.) and psoriatic arthritis. One criterion was excluded: The criterion type of preventive benefit was excluded, as the drugs being assessed in this MCDA are focused on the treatment of the disease, and not on its prevention.
Disease severity	Absolute
Size of affected population	Absolute
Unmet needs	Absolute
Outcomes of the intervention
Level of clearance	Relative
Rapidity of clearance	Relative
Persistence of clearance	Relative
Safety/tolerability	Relative
Patient reported outcomes	Relative
Type of benefit of the intervention
Type of therapeutic benefit	Absolute
Consistency of the effect	Relative
Economic consequences of the intervention
Cost of intervention	Relative
Impact on other direct costs	Relative
Impact on indirect costs	Relative
Knowledge about the intervention
Quality of evidence	Absolute
Expert consensus/clinical practice guidelines	Relative

Absolute criterion: does not contemplate comparisons between interventions. Scores range from 0 to 5, with 0 being the lowest value and 5, the highest. Relative criterion: it is used when comparing bimekizumab with placebo or another drug. Scores range from −5 (bimekizumab is much worse than the comparator) to 5 (bimekizumab is much better than the comparator)

Figure 1. Relative importance of each individual criterion in the assessment of drugs for the treatment of moderate-to-severe psoriasis (mean, min, max and median weights and standard deviations). The 100-points distribution method was applied, by which the experts assigned a weight to each criterion, provided its aggregation resulted in 100. CPG: clinical practice guidelines.

Table 2. Scores assigned per criterion, and main comments from the multidisciplinary experts committee or observation of subgroup results.

Criterion		Scores (box-and-whisker plot) *				Comments
Need for the intervention
Disease severity						Moderate-to-severe psoriasis was considered as a severe disease. This high score is due to the consideration of moderate-to-severe psoriasis as a whole, as there are many differences between moderate and severe psoriasis. It has a high impact on patients’ quality of life, work environment, and emotional (psychological and psychiatric) spheres. It is not a life-threatening disease. Other skin diseases, such as melanoma, are more serious. Median scores for all subgroups were 4.0.
Size of affected population						There was a consensus (10 out of 12 experts scored 3.0) around the prevalence of psoriasis: 2,3% of the total population in Spain has psoriasis, and 0.6% has moderate-to-severe psoriasis. The difficulty lies in quantifying patients with moderate-to-severe psoriasis who require biologic treatments and those who can be treated with conventional systemic drugs. One of the experts commented that the estimated figure for the population with moderate-to-severe psoriasis in Spain (0.6% of the population) may be underestimated, arguing that, due to economic criteria, such as avoiding or delaying the entry into higher-cost treatments, some patients may be diagnosed as having mild-to-moderate psoriasis. Median scores for all subgroups were 3.0.
Unmet needs						Experts considered that moderate-to-severe psoriasis is a disease with considerable unmet needs. Lower scores were assigned by those who considered only the clinical unmet needs, as the existing therapeutic arsenal provides very effective treatments. Higher scores considered other needs, such as psychological support and access to therapies. Healthcare professionals considered the unmet needs to be lower (median: 3.0), in comparison to other groups (4.0).
Outcomes of the intervention
Level of clearance								Interpretation of the results: a score of 5.0 means that bimekizumab is much better than the comparator in relation to level of clearance achieved. Experts agreed with the results, adding that, for all efficacy criteria, they would have expected an absolute consensus of a 5.0 score in the comparison between BKZ and PBO (median was 5.0 in all). Also, experts believe the results between BKZ vs. SEC and BKZ vs. IXE should have been similar (medians are identical, despite different average scores). Results of the subgroups were similar to the overall scores. The exceptions lie in the comparison BKZ vs. SEC (median; patients: 3.5; other groups: 2.0), and BKZ vs. IXE and RIS (healthcare professionals scored the lowest, whilst managers scored the highest).
Rapidity of clearance								Interpretation of the results: a score of 5.0 means that bimekizumab is much faster than the comparator in achieving clearance targets. This results are in line with the evidence analysed, reflecting that the IL-17 (BKZ, SEC, and IXE) are the drugs, which provide the fastest onset of action. Bimekizumab appears to be the drug that delivers the fastest onset of action. Subgroup results the same as to those obtained globally, with three exceptions: BKZ vs. SEC (medians; healthcare professionals: 2.0; other groups: 3.0); BKZ vs. IXE (1.0, 2.0, and 2.5 for healthcare professionals, managers, and patients, respectively); BKZ vs. RIS (median; healthcare professionals: 3.0; patients: 3.5; managers: 4.0).
Persistence of clearance								Interpretation of the results: a score of 5.0 means that bimekizumab is much better than the comparators in maintaining the level of clearance over time. According to the experts, more long-term results and data from real clinical practice are needed to assess persistence after the first year. They added that secukinumab is a drug, which usually loses efficacy in the long-run. Overall, for all comparisons except BKZ vs. PBO, healthcare professionals assigned lower scores (medians between 0.0 and 3.0) in relation to the other groups (managers and patients: 3.0-4.0).
Safety / tolerability								Interpretation of the results: a score of 5.0 means that bimekizumab is much safer and tolerable than the comparator, whilst a score of -5.0 means that bimekizumab is less safe and tolerable than the comparator. The experts commented that bimekizumab, overall, has a similar safety/tolerability profile compared to most of the comparators. Some of the low scores assigned to this drug could be explained by the adverse events related to candidiasis, although the experts highlighted that this is perfectly manageable, not leading to treatment discontinuation. Variability in the scores was high (SD 1.1-2.6) which could be related to the difference in importance given by each expert to the different types of adverse events (total, serious, severe, etc.) produced by the use of the drugs. Healthcare professionals and managers tended to assign lower scores (mostly between -1.0 and 1.0) than patients (1.5 to 2.0).
Patient reported outcomes								Interpretation of the results: a score of 5.0 means that bimekizumab is much better than the comparator in achieving patient reported outcomes. Patient reported outcomes were valued based on quality-of-life scales and convenience of treatment. The experts mentioned that this made scoring and interpretation more difficult. According to the experts, there tends to be a correlation between patient reported outcomes and the level of clearance achieved by the use of the drugs. Hence, it became more complex to score this criterion in an independent manner. Convenience entails aspects, which not only are related to the frequency of doses, but also to the pain caused by the shots and induction periods. Excluding the comparison between BKZ vs. PBO, the highest scores on patient reported outcomes were assigned by the patients (medians between 2.0 and 3.0), related to other groups (healthcare professionals and managers: 0.0-3.0).
Type of benefit of the intervention
Type of therapeutic benefit										The drug provides a substantial therapeutical benefit to the patients, as it improves results reported by the patients (quality of life and symptoms such as pain, itching, and flaking), and combines a higher level of clearance, rapidity, and persistence with a similar safety and tolerability profile. Despite of not providing a (desirable) cure, bimekizumab represents a step forward in the treatment of moderate-to-severe psoriasis, even considering the sizable number of alternative therapies available. Managers scored a median of 3.0, whilst the other subgroups had a median score of 4.0.
Consistency of the effect										Interpretation of the results: a score of 5.0 means that the effects of bimekizumab are much more consistent in the treatment of psoriatic arthritis and specific locations of psoriasis (i.e. scalp, nails, palmoplantar, genitals) that those of the comparator. Some of the experts based their score on the existence of an approval for psoriatic arthritis (i.e. risankizumab has not yet been approved to this indication). Others also considered aspects that stand out in each drug (i.e. secukinumab for the treatment of nail psoriasis, or risankizumab for the treatment of genital psoriasis). There are interrelations between some effects: efficacy of psoriatic arthritis and nail psoriasis; efficacy on general level of clearance and scalp psoriasis. Variability on the answers between subgroups was high, and no clear pattern was revealed (i.e. no group scored the highest or the lowest across all comparisons).
Economic consequences of the intervention
Cost of intervention									Interpretation of the results: a score of 5.0 means that the acquisition of bimekizumab generates substantial savings to the system versus the comparator, whilst a score of -5.0 means that it generates substantial additional costs. In the absence of a price for bimekizumab in Spain (not defined at the time this study was being carried on), we assumed the same annual acquisition cost per patient as that of an IL-17A inhibitor already marketed, such as secukinumab. Thus, a cost per patient of €19,400 was assumed for the first year and €14,900 for the maintenance period, based on notified prices (laboratory sales prices: PVL). The MEC mentioned that this was a very reasonable assumption. Experts recognized that there is a large difference between the notified price and the ones practiced by the market, especially for the biologics that have biosimilars. For this reason, some of the scores of bimekizumab vs. adalimumab took into account the real cost of adalimumab (indicated to be around €3,500 p.a.). This explains the highest variability observed between the scores assigned in this comparison. Healthcare professionals assigned a score of 0 for all comparisons except BKZ vs. ADA and BKZ vs. PBO. Patients assigned scores between 0.0 and -0.5 (except BKZ vs. PBO) and managers gave scores between -2.0 and 1.0 (except BKZ vs. PBO).
Impact on other direct costs									Interpretation of the results: a score of 5.0 means that bimekizumab would generate substantial savings in other direct costs (hospitalizations, medical visits, etc.) in relation to the comparator. The median score for all comparisons (except BKZ vs. PBO) was 1.0, and there were no negative scores assigned, reflecting that bimekizumab appears to be slightly superior in terms of the impact that its implementation would have on other direct costs. Experts commented that the results obtained are consistent, given the limited available evidence. Variability was low between subgroups. Median scores for all comparisons (except BKZ vs. PBO) were 1.0 for the managers, between 0 and 1 for healthcare professionals and between 1.0 and 2.5 for patients.
Impact on indirect costs							Interpretation of the results: a score of 5.0 means that bimekizumab would generate substantial savings in indirect costs (i.e. labor productivity) in relation to the comparator. The results appear to be consistent, in the opinion of the experts. The impact of psoriasis on patients’ work activity generated certain differences of opinions among the committee members. For some experts, it may have little impact, while for others, this impact may be greater due to logistical issues, such as the need for medical visits, or to pick up medications from the hospital pharmacy. Some commented that, in this sense, home dispensing and teleconsultation have resulted in labor productivity improvements. Variability was low between groups and no scores were extreme cases. Median scores for all comparisons (except BKZ vs. PBO) were 1.0 for the managers, between 0 and 2 for healthcare professionals and between 1.5 and 2.5 for patients
Knowledge about the intervention
Quality of evidence							Interpretation of the results: a score of 5.0 means that the quality of the evidence on which the comparison data are based upon is highly relevant and valid, whilst a score of 0.0 means that it is neither relevant or valid. The quality of evidence generated by the four head-to-head trials (direct comparisons: BKZ vs. PBO, ADA, UST, and SEC) was considered as very relevant and valid, whilst the indirect comparisons (BKZ vs. IXE and RIS) were considered relatively less relevant, as the comparisons had less scientific rigor (“eyeball” comparisons). All experts have identical scores for the BKZ vs. IXE and BKZ vs. RIS comparisons. For the head-to-head trials, healthcare professionals assigned median scores of 5.0 (patients: 4.5; managers: 4.0). For the indirect comparisons, median scores from the healthcare professionals and managers were 2.0 (patients: 4.0).
Expert consensus / CPG							Interpretation of the results: a score of 5.0 means that bimekizumab is or will be better recommended than the comparator, and -5.0 means that the comparator is or will be better recommended than bimekizumab in future clinical practice guidelines updates or expert consensus. The MEC considered that bimekizumab will be positioned similarly to other first-line biological drugs for the treatment of moderate-to-severe psoriasis in the future updates of clinical practice guidelines. According to them, some of the elements that could differentiate bimekizumab from the others are the form of administration (every 2 months); the potential approval for the treatment of psoriatic arthritis and the maintenance of efficacy levels. Overall, patients have assigned the highest scores to this criterion (medians between 1.5 and 3.5, excluding the comparison of BKZ vs. PBO), whilst healthcare professionals and managers assigned similar scores (mostly between 1.0 and 2.0)

*The box-and-whisker plot visually represents various descriptive statistics of the scores given for this criterion. The lower and upper limits of the graph represent the minimum and maximum scores. The box represents the central 50% of the scores awarded, as it is bounded by the lower (25%) and upper (75%) quartile. The ”x” represents the average value of the scores, and the line dividing the boxes (which is the number that appears on the table) represents the median (in some cases, the median coincides with one of the two quartiles represented graphically). The circles represent the extreme cases (“outliers”), which show scores that deviate more than 1.5 times from the interquartile ranges. Finally, greater distances between the extremes of the box and the graph represent greater dispersion in the responses. CPG: clinical practice guidelines. BKZ: Bimekizumab. PBO: placebo. ADA: Adalimumab. UST: Ustekinumab. SEC: Secukinumab. IXE: Ixekizumab. RIS: Risankizumab.

Figure 2. Value contribution of bimekizumab compared to placebo and five biological drugs according to the MCDA framework for the assessment of drugs in moderate-to-severe psoriasis. Mean value contribution per domain and overall value estimates are shown. Error bars show standard deviations across the twelve participants. BKZ: Bimekizumab. PBO: placebo. ADA: Adalimumab. UST: Ustekinumab. SEC: Secukinumab. IXE: Ixekizumab. RIS: Risankizumab.

Data availability statement

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.