Understanding characteristics of patients newly initiating ixekizumab: findings from the Corrona Psoriasis Registry

Table 1 presents patient demographics and comorbidities at enrollment for patients initiating ixekizumab and those initiating other biologics. Our study included 2963 patients, of which 388 were ixekizumab initiators. The mean age for patients initiating ixekizumab was similar to patients initiating other biologics (50.3 vs 49.2 years). The proportion of males in both groups (ixekizumab vs other biologics) was similar, 54 versus 52%, respectively. The distribution of body mass index (BMI) differed with more patients who were ixekizumab initiators in the overweight group (31 vs 30%) and obese group (54 vs 47%) than patients initiating other biologics (p = 0.006). More patients initiating ixekizumab had private health insurance (83 vs 76%) than those initiating other biologics (p = 0.004).

Initiators of ixekizumab had a higher prevalence of hypertension (42 vs 36%; p = 0.014) and hyperlipidemia (31 vs 26%; p = 0.062) than initiators of other biologics. On medical history at enrollment, there were no significant differences in rates of prior tuberculosis (3 vs 4%), cardiovascular disease (4 vs 5%), lymphoma/malignancy (4 vs 4%), anxiety (18 vs 19%), and depression (19 vs 19%) between ixekizumab initiators and other biologics initiators.

Table 2 displays patient disease characteristics at enrollment for patients initiating ixekizumab and those initiating other biologics. Patients initiating ixekizumab had more inverse/intertriginous (10 vs 7%; p = 0.018), nail (19 vs 14%; p = 0.007), and palmoplantar (12 vs 9%; p = 0.051) morphologies than patients initiating other biologics. Psoriasis duration and PsA duration (among those with a history of PsA) were longer for initiators of ixekizumab than for initiators of other biologics (17.1 vs 15.1 years; p = 0.007) and (8.6 vs 6.9 years; p = 0.016), respectively. Patients initiating ixekizumab had a greater distribution of patients with IGA moderate and severe (56 vs 48%; p < 0.0001), and significantly higher mean PASI scores than patients initiating other biologics (7.5 vs 5.7; p < 0.0001), respectively. Likewise, ixekizumab initiators had a significantly higher proportion of patients with PASI greater than 10 (28 vs 19%, respectively; p <0.0001), and also a greater proportion of patients were in the severe and very severe BSA categories (33 vs 26%; p = 0.009), respectively.

Table 3 presents PROs at enrollment for patients initiating ixekizumab and those initiating other biologics. Ixekizumab initiators and other biologics initiators experienced similar mean VAS scores for skin pain (23.6 vs 23.6) and fatigue (30.1 vs 30.7), respectively. Likewise, both groups reported similar health-related QoL as measured by the DLQI (7.0 vs 6.8) and DLQI ‘Effect on Life’, with more than 44% in both groups experiencing a moderate or very large impact on their lives. Slightly more patients initiating ixekizumab were currently employed than those initiating other biologics (73 vs 69%). Both patient groups were similar for percent of impairment while working due to PsO (12.5 vs 11.9%) and percent of daily activities impaired by PsO (19.6 vs 18.1%). However, patients initiating ixekizumab had significantly higher percent mean work hour missed compared with those initiating other biologics (5.3 vs 2.9%; p = 0.005).

Table 4 displays treatment status and medication histories at enrollment for patients initiating ixekizumab and those starting other biologics. A significantly lower proportion of patients initiating ixekizumab were biologic-naive than that of patients initiating other biologics (20 vs 52%; p < 0.0001), and a significantly greater proportion of patients initiating ixekizumab had used at least two or more prior biologics than those initiating other biologics (70 vs 49%; p < 0.0001). A significantly lower proportion of ixekizumab initiators were naive to non-biologics than that of other biologics initiators (43 vs 52%; p = 0.0006), and among those with prior non-biologic use, a significantly higher proportion of ixekizumab initiators group had used at least two or more non-biologics than that of other biologics initiators (41 vs 26%; p < 0.0001). Approximately 12% of patients in both therapy groups had concomitant use of non-biologic therapy a biologic initiation (data not shown).

In our study, we found patients newly initiating ixekizumab were more likely to have involvement of hard-to-treat areas (inverse/intertriginous, nail, and palmoplantar). They had a longer duration with PsO and PsA, as well as more severe disease than those newly initiating other biologics, based on three disease severity measures (PASI, BSA, and IGA). Likewise, initiators of ixekizumab had more significant proportions of patients with higher overall itch and percent mean work hours missed than initiators of other biologics. In addition to observing that more patients initiating ixekizumab were biologic experienced, these clinical characteristics demonstrate that in the real-world, ixekizumab is predominantly being used by patients with more severe PsO and as a later line of therapy.

The observation that more patients initiating ixekizumab had more severe PsO (56% IGA moderate and severe or 33% BSA severe and very severe) and that most of them had used two or more biologic therapies previously (70%) than those initiating other biologics, may imply that patients prescribed ixekizumab are more severe PsO patients and or are likely to be resistant to other treatments. The use of ixekizumab among more severe PsO patients and its higher use among patients likely to have involvement of hard-to-treat areas could be attributed to the robust efficacy evidence and safety profile demonstrated by numerous clinical studies [8,11–13,24].

In head-to-head trials, ixekizumab has been shown to have superior efficacy compared with eternacept (UNCOVER-2 and UNCOVER-3) [25], ustekinumab (IXORAS-S) [26], and guselkumab [27]. Further, ixekizumab has been associated with rapid improvement in health-related QoL and itch [28], work productivity [29], and both nail [30] and scalp [31] PsO. While the evidence on the high efficacy of ixekizumab among patients who are potentially resistant to other biologics may support using it as a later line therapy, a recent study has shown that ixekizumab is highly efficacious among biologic-naive patients similarly to biologic-experienced patients [32].

Our findings that most patients initiating ixekizumab were biologic-experienced, and had used at least two prior biologics, could, in part, be explained by limitations to access. Some insurance policy plans have incorporated restrictions on treatment choice, such as step-therapy policies that require payer preferred medications before being prescribed newer biologics [33]. These policies can impede providers from prescribing drugs in the sequence and order that they feel will result in the best outcomes for their patients.

The argument for access restriction policies is improved quality and economic benefit [34]. However, a recent study that compared treatment effectiveness among rheumatoid arthritis and PsA patients with and without plan-level access restrictions to biologic disease modifying antirheumatic drugs (DMARDs) or targeted synthetic DMARDs (tsDMARDs), found patients in plans without access restrictions or with prior authorization only, rheumatoid arthritis and PsA patients in insurance plans with step therapy had lower odds of treatment effectiveness [35]. Moreover, the Institute for Clinical and Economic Review (ICER) concluded in a recent review that IL-17 inhibitors were highly efficacious, had reasonable economic value, and were reasonable first-line targeted treatments [35,36].

Limitations to access and patient and provider preferences may, at least in part, explain the different use of ixekizumab among biologic-naive patients. Factors that play a role in the decision-making process for both the provider and patient, including provider clinical inertia, defined as the failure of healthcare providers to initiate or intensify therapy when indicated [37] and or a patient’s unwillingness to switch therapies due to fear of side effects [38], could potentially lead to delays in realizing treatment benefits among these patients. Studies have shown that poor results and reduced patient satisfaction has been attributed to the lack of confidence many physicians exhibit when prescribing systemic drugs, especially biologics [39].

While our study has several integral strengths, including the use of data from an extensive national disease registry with patients from academic and private practice dermatologists who are likely to reflect a typical real-world patient population in the US, as with any observational registry, it is not without limitations. The results may not be generalizable to others outside of the US because the data are from a US registry. Information bias may have been introduced because measures were assessed and collected by multiple providers; however, we strived to reduce this bias by using validated data collection instruments where possible. Selection bias could have been introduced by the voluntary participation of dermatologists and patients. To minimize the selection bias leading to highly correlated characteristics due to lack of adjustments, we only present descriptive findings.

Future studies should evaluate longitudinal effectiveness, QoL outcomes, safety, and treatment patterns among users of ixekizumab in the real-world. Likewise, comparative effectiveness studies comparing results of ixekizumab users to users of other biologics by line of therapy would provide valuable insights for treatment choice. Similarly, studies evaluating the impact of barriers to treatment access on treatment outcomes and treatment choice would be informative.

In this real-world study from routine clinical practice data, we found that patients’ newly initiating ixekizumab were more likely to be obese, biologic-experienced, and have involvement in hard-to-treat areas. These patients had more severe PsO, and most reported a more substantial impact on work productivity and worse QoL than patients initiating other biologics. The use of ixekizumab predominantly among more severe and biologic-experienced PsO patients may be attributed, in part, to its proven efficacy and safety profile, as well as possible formulary management restrictions.

Clinical effectiveness information and scientific knowledge are essential for the effective and safe use of the increasingly complex and diverse treatment options for physicians and patients in psoriatic diseases. As more innovative PsO treatment options grow, a robust paradigm to guide clinical decision making in clinical practices in necessary.

Each author listed participated sufficiently in the work to take responsibility for the content, and all those who qualify are listed.

Michelle D. Karpman, PhD, Corrona LLC, provided scientific writing support funded by Eli Lilly and Company. The authors would like to thank all the investigators, their clinical staff, and patients who participate in the Corrona Psoriasis® Registry.

The Corrona Psoriasis Registry is sponsored by Corrona LLC. Corrona LLC has been supported through contracted subscriptions in the last two years by AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly and Company, Genentech, Gilead, Janssen, Momenta, Novartis, Ortho Dermatologics, Pfizer Inc., Regeneron, Sanofi and Sun. Author declarations of interest: JJ Wu, Amgen, Bristol Myers Squibb, Celgene, Dermira, Dr Reddy’s Laboratories, Eli Lilly and Company, Janssen, LEO Pharma, Novartis, Promius Pharma, Regeneron, Sun Pharmaceutical, and UCB, Valeant Pharmaceuticals North America LLC; and a speaker for AbbVie, Celgene, Novartis, Regeneron, Sanofi Genzyme, Sun Pharmaceutical, UCB, Valeant Pharmaceuticals North America LLC; RW Harrison, Employee Corrona LLC; B Zhu, Employee/Stock, Eli Lilly and Company; OM Goldblum, Employee/Stock, Eli Lilly and Company; WN Malatestinic, Employee/Stock, Eli Lilly and Company; R Burge, Employee/Stock, Eli Lilly and Company; MJ Murage, Employee/Stock, Eli Lilly and Company. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

MD Karpman, Corrona LLC, provided scientific writing support funded by Eli Lilly and Company.

All participating investigators were required to obtain full board approval for conducting research involving human subjects. Study approval and continuing review was obtained through a central IRB (IntegReview, Protocol number is Corrona-PSO-500). All registry subjects were required to provide written informed consent prior to participating.

The Corrona dataset is based on a large US North American multicenter study adhering to a number of institutional review boards, with complex logistics. Patients did not provide consent to raw data sharing during the data collection for this purpose, and the Corrona data sharing policies do not permit raw data sharing for this purpose. An aggregated limited dataset from the current analyses is available to qualified investigators with an approved protocol. Data requests may be sent to Corrona, represented by JD Greenberg, NYU School of Medicine, New York, NY, e-mail [email protected].