Managing the dose escalation of biologics in an era of cost containment: the need for a rational strategy

Shahwan, Kathryn T.; Kimball, Alexa B.

doi:10.1016/j.ijwd.2016.09.003

Cited by 13 publications

(19 citation statements)

References 13 publications

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“…22,23 If the dose is inadequate, dose escalation may be necessary. 24,25 With the data presented here, and additional population PK modelling and exposure-response modelling analyses outlined above, as well as the comprehensive efficacy and safety assessments in Phase 3, the method for dose selection in the guselkumab psoriasis programme was robust and yielded the optimal, convenient dosing regimen of 100 mg at weeks 0, 4, then q8w for the broader population of moderate-to-severe psoriasis patients.…”

Section: Discussionmentioning

confidence: 92%

Use of dose–exposure–response relationships in Phase 2 and Phase 3 guselkumab studies to optimize dose selection in psoriasis

Lebwohl

Langley

Zhu

et al. 2019

Acad Dermatol Venereol

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Background Guselkumab is an anti‐interleukin‐23 monoclonal antibody for the treatment of moderate‐to‐severe psoriasis. Objective To evaluate the association between dose–response and exposure–response of guselkumab in Phase 2 and Phase 3 studies to optimize dose selection. Methods Serum guselkumab concentrations in Phase 2 and Phase 3 studies (VOYAGE 1 and VOYAGE 2) were measured using a validated immunoassay. Efficacy assessments included Physician's Global Assessment (PGA), Investigator's Global Assessment (IGA) and Psoriasis Area and Severity Index (PASI). Results In Phase 2, a positive dose–response relationship was observed for PASI and PGA (5‐mg through 100‐mg dose regimens). Exposure–response analysis showed that patients with steady‐state trough serum guselkumab concentrations ≥0.67 μg/mL achieved the highest levels of efficacy (PGA 0/1: 90.0%; PGA 0: 70.0%). The guselkumab 100‐mg every 8‐week (q8w) dose regimen, safe and well‐tolerated in Phase 2, provided the highest serum guselkumab concentrations among all regimens studied and was selected for Phase 3. In Phase 3, 72.5% of patients achieved guselkumab concentrations ≥0.67 μg/mL at week 28, the level associated with the highest clinical responses in Phase 2, with patients achieving response rates of IGA 0/1: 91.2%, IGA 0: 55.3%, PASI 90: 83.8% and PASI 100: 49.1% at week 28. Conclusion The 100‐mg guselkumab q8w dose regimen, based on the dose–exposure–response relationship from the Phase 2 study, produced the target serum concentration associated with high‐level efficacy in the majority of patients in Phase 3. Phase 3 data further confirmed that guselkumab 100mg q8w is the optimum dosing regimen for treating patients with moderate‐to‐severe psoriasis.

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Section: Discussionmentioning

confidence: 92%

Use of dose–exposure–response relationships in Phase 2 and Phase 3 guselkumab studies to optimize dose selection in psoriasis

Lebwohl

Langley

Zhu

et al. 2019

Acad Dermatol Venereol

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“…Dose escalation is the simplest strategy and is generally well tolerated; however, it confers a significant cost burden because doubling the dosage is likely to double the wholesale price. 17 The use of biologics represents an important and cumulative cost that affects the healthcare pharmaceutical budget. 18 Therefore, optimizing the use of therapeutic resources could be very important.…”

Section: Discussionmentioning

confidence: 99%

Efficacy of secukinumab without the initial weekly loading dose in patients with chronic plaque psoriasis

et al. 2019

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Summary Background Secukinumab is administered at the labelled dose of 300 mg at weeks 0, 1, 2, 3, 4 (loading dose) and every 4 weeks thereafter. Objectives To investigate the efficacy of secukinumab administered without the initial loading dose in patients with psoriasis. Methods This was a retrospective observational study including adult patients with psoriasis (n = 156) treated with secukinumab 300 mg administered either according to the labelled dose (n = 75) or without the initial loading dose (n = 81). Efficacy was evaluated by comparing the Psoriasis Area and Severity Index (PASI) 75 and PASI 90 response rates at week 8, 12, 16, 32 and 48. Results For patients who received the labelled dose vs. those who did not, PASI 75 response rates were achieved at week 8, 12, 16, 32 and 48 by 60% vs. 40% (P < 0·01), 72% vs. 61% (P < 0·01), 77% vs. 75%, 85% vs. 77% and 79% vs. 78%, respectively. PASI 90 responses were achieved at the same time points by 45% vs. 31% (P < 0·01), 49% vs. 40% (P < 0·01), 54% vs. 47%, 55% vs. 47% and 57% vs. 54% for those who received the labelled dose vs. those who did not, respectively. A greater proportion of patients receiving secukinumab without the loading dose discontinued treatment because of inefficacy (25% vs. 13%, P < 0·05), particularly those with body weight greater than 80 kg. Conclusions Secukinumab administered without the loading dose is associated with a higher proportion of primary inefficacy, and achieved inferior results compared with the labelled dose at week 8 and week 12, but showed similar efficacy thereafter. What's already known about this topic? Secukinumab is an interleukin (IL)‐17A inhibitor for chronic plaque psoriasis administered by subcutaneous injections at the labelled dose of 300 mg at weeks 0, 1, 2, 3, 4 (loading dose) and every 4 weeks thereafter (maintenance dose). Dose adjustment is common in clinical practice, and can consist of dose reduction when a prolonged remission is obtained or a dose increase in order to improve efficacy. What does this study add? The efficacy of secukinumab administered without the initial weekly loading dose was significantly inferior compared with the labelled dose in the short term, but was similar after week 16 and up to week 48. A greater proportion of patients receiving secukinumab without the loading dose showed primary inefficacy, particularly those with body weight greater than 80 kg.

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“…37 Dose optimization may also be required for ixekizumab and secukinumab, which can lead to greater efficacy in some patients with moderate-to-severe psoriasis, but also result in higher treatment costs. 38,39 As complete skin clearance is rapidly becoming the new standard for treatment of moderate-tosevere psoriasis, dose escalation may be practiced to an increasing extent to gain a greater amount of improvement in skin clearance, such as achieving PASI 100 versus PASI 75. Initial above-label dosing and dose escalation of biologic drugs present difficult scenarios in the management of patients with moderate-to-severe psoriasis, since biologic drugs generally demonstrate better efficacy at higher doses in patients who did not respond to treatment at lower doses, [38][39][40] but can result in substantial increases in treatment costs.…”

Section: Perspectives On Treating Patients With Moderate-to-severe Psmentioning

confidence: 99%

“…38,39 As complete skin clearance is rapidly becoming the new standard for treatment of moderate-tosevere psoriasis, dose escalation may be practiced to an increasing extent to gain a greater amount of improvement in skin clearance, such as achieving PASI 100 versus PASI 75. Initial above-label dosing and dose escalation of biologic drugs present difficult scenarios in the management of patients with moderate-to-severe psoriasis, since biologic drugs generally demonstrate better efficacy at higher doses in patients who did not respond to treatment at lower doses, [38][39][40] but can result in substantial increases in treatment costs. 38 Strategies other than dose-escalation, such as switching to another biologic drug, in the treatment management of non-responders may not only be more efficacious, but also help in containing treatment costs.…”

Section: Perspectives On Treating Patients With Moderate-to-severe Psmentioning

confidence: 99%

“…Initial above-label dosing and dose escalation of biologic drugs present difficult scenarios in the management of patients with moderate-to-severe psoriasis, since biologic drugs generally demonstrate better efficacy at higher doses in patients who did not respond to treatment at lower doses, [38][39][40] but can result in substantial increases in treatment costs. 38 Strategies other than dose-escalation, such as switching to another biologic drug, in the treatment management of non-responders may not only be more efficacious, but also help in containing treatment costs. 38 For brodalumab, the prescribing information does not recommend dose escalation, 41 and in its case the difficult scenarios of initial above-label dosing and dose escalation would largely be preempted.…”

Section: Perspectives On Treating Patients With Moderate-to-severe Psmentioning

confidence: 99%

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Evaluating Costs of Biologic Drugs for the Treatment of Moderate-to-Severe Psoriasis in the United States

Feldman

Armstrong

et al. 2019

Journal of Psoriasis and Psoriatic Arthritis

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Objective:To provide a contemporary comparative assessment of biologic drug costs and cost effectiveness for treating moderate-to-severe psoriasis in the United States.Methods:A literature search was conducted in PubMed on October 4, 2018 with the search terms of “psoriasis,” “biologic,” and “cost” with a filter of publication dates within the last 5 years (2014-2018). Studies included in this review were required to be conducted from a United States perspective.Results:Of the 16 studies retrieved, the costs associated with use of biologic drugs for the treatment of moderate-to-severe psoriasis were relatively high, with some drugs exhibiting sustained lower costs than others. Some comparative findings on the cost-effectiveness of biologic drugs based on the annual treatment cost per Psoriasis Area and Severity Index (PASI) 75 responder concluded that the annual treatment cost was lowest for brodalumab 210 mg at US$48 782; the cost was highest for ustekinumab 45/90 mg (US$87 243), followed by adalimumab 40 mg (US$82 655), ixekizumab 160 mg (US$77 957), and secukinumab 300 mg (US$75 671). The annual treatment cost per PASI 100 responder was also lowest for brodalumab at US$87 585. This pattern remained consistent in other cost studies, with brodalumab being the treatment with the lowest treatment costs when compared to other biologic drugs.Conclusion:Brodalumab was consistently observed to be the least costly treatment option among biologic drugs used to treat moderate-to-severe psoriasis in the United States, which is largely the result of its low-drug cost and high-PASI response rate.

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Managing the dose escalation of biologics in an era of cost containment: the need for a rational strategy

Cited by 13 publications

References 13 publications

Use of dose–exposure–response relationships in Phase 2 and Phase 3 guselkumab studies to optimize dose selection in psoriasis

Use of dose–exposure–response relationships in Phase 2 and Phase 3 guselkumab studies to optimize dose selection in psoriasis

Efficacy of secukinumab without the initial weekly loading dose in patients with chronic plaque psoriasis

Evaluating Costs of Biologic Drugs for the Treatment of Moderate-to-Severe Psoriasis in the United States

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