Along with co-authors from ICER and The CHOICE Institute, I recently published a paper in JMCP titled, “Cost-effectiveness of targeted pharmacotherapy for moderate-to-severe plaque psoriasis.” In this publication, we sought to update estimates of cost-effectiveness for systemic therapies useful in the population of patients with psoriasis for whom methotrexate and phototherapy are not enough.
Starting in 1998, a class of drugs acting on Tumor Necrosis Factor alpha (TNFɑ) has been the mainstay of psoriasis treatment in this population. The drugs in this class, including adalimumab, etanercept, and infliximab, are still widely used due to their long history of safety and lower cost than some competitors. They are less effective than many new treatments, however, particularly drugs inhibiting interleukin-17 such as brodalumab, ixekizumab, and secukinumab.
This presents a significant challenge to decision-makers: is it better to initiate targeted treatment with a less effective, less costly option, or a more effective, costlier one? We found that the answer to this question is complicated by several current gaps in knowledge. First, there is some evidence that prior exposure to biologic drugs is associated with lower effectiveness in subsequent biologics. This means that the selection of a first targeted treatment must balance cost considerations with the possibility of losing effectiveness in subsequent targeted treatments if the first is not effective.
A related issue is that the duration of effectiveness (or “drug survival”) for each of these drugs is currently poorly characterized in the US context. Drug discontinuation and switching is significantly impacted by policy considerations such as requirements for step therapy and restrictions on dose escalation. Therefore, while there is a reasonable amount of research about drug survival in Europe, it is not clear how well this information translates to the US.
Another difficulty of performing cost-effectiveness research in this disease area is the difficulty of mapping utility weights onto trial outcomes. Every drug considered in our analysis used percentage change in the Psoriasis Area Severity Index (PASI) over baseline. Because this is not an absolute measure, it required that we assume that patients have comparable baseline PASI scores between studies. In other words, we had to assume that a given percent improvement in PASI was equivalent to a given increase in health-related quality of life. This means that if one study’s population had less severe psoriasis at baseline, we probably overstated the utility benefit of that drug.
In light of these gaps in knowledge, our analytic strategy was to model a simulated cohort of patients with incident use of targeted drugs. After taking a first targeted drug, they could be switched to a second targeted drug or cease targeted therapy. We made the decision to limit patients to two lines of targeted treatment in order to keep the paper focused on the issue of initial treatment.
What we found is a nuanced picture of cost-effectiveness in this disease area. In agreement with older cost-effectiveness studies, we found that infliximab is the most cost-effective TNFɑ drug and, along with the PDE-4 inhibitor apremilast, is likely to be the most cost-effective treatment at lower willingness-to-pay (WTP) thresholds. However, at higher WTP thresholds of $150,000 per quality-adjusted life year and above, we found that the IL-17 inhibitors brodalumab and secukinumab become more likely to be the most cost-effective.
The ambiguity of these results suggests both the importance of closing the gaps in knowledge mentioned above and of considering factors beyond cost-effectiveness in coverage decisions. For example, apremilast is the only oral drug we considered and patients may be willing to trade lower effectiveness to avoid injections. Another consideration is that IL-17 inhibitors are contraindicated for patients with inflammatory bowel disease, suggesting that payers should make a variety of drug classes accessible in order to provide for all patients.
In summary, these results should be seen as provisional, not only because many important parameters are still uncertain, but also because several new drugs and biosimilars for plaque psoriasis are nearing release. Decision-makers will need to keep an eye on emerging evidence in order to make rational decisions about this costly and impactful class of drugs.