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Novel Psoriasis Therapies and Patient Outcomes, Part 2: Biologic Treatments

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Novel Psoriasis Therapies and Patient Outcomes, Part 2: Biologic Treatments Novel Psoriasis Therapies and Patient Outcomes, Part 2: Biologic Treatments Meghan A. Feely, MD; Barry L. Smith, MD; Jeffrey M. Weinberg, MD Practice Points Novel biologic treatments promise exciting new therapeutic avenues for psoriasis and psoriatic arthritis (PsA). Although biologics currently in use for treatment of psoriasis and PsA are in the form of tumor necrosis factor α inhibitors, other drugs in phase 2 through phase 4 clinical trials aim to target alternative pathways underlying the pathogenesis of these disorders, including IL-12/IL-23 inhibition, IL-17 inhibition, inhibition of T-cell activation in antigen-presenting cells, regulatory T-cell activation, toll-like receptor inhibition, and granulocyte-macrophage colony-stimulating factor inhibition. New approaches to the management of psoriasis and PsA offer patientscopy hope for more targeted treat- ment regimens. not Biologic treatments have revolutionized the man- second in a 3-part series on treatments presently agement of psoriasis and psoriatic arthritis (PsA).Do in the pipeline for the management of psoriasis Anti–tumor necrosis factor (TNF) α monoclo- and PsA including topical agents, biologic treat- nal antibodies presently are approved by the ments, and systemic therapies in phase 2 through US Food and Drug Administration (FDA) for treat- phase 4 clinical trials as well as agents that are ment of these conditions. In this article, new recently FDA approved. Pivotal clinical trials, therapies that target this pathway and other steps mechanisms of action, patient outcomes, and in the pathogenesis of psoriasis and PsA are dis- pertinent safety information will be discussed for cussed, including IL-12/IL-23, IL-17, T-cell activa- each new therapy. As our knowledge of the under- tion in antigen-presenting CUTIScells, regulatory T cells, lying pathogenesis of psoriasis and PsA deepens, toll-like receptors, and granulocyte-macrophage it enables the development of more targeted colony-stimulating factor. This article is the therapies in the management of these conditions. Cutis. 2015;95:282-290. iologic agents that currently are in use for the management of moderate to severe psoriasis and From the Department of Dermatology, Mount Sinai St. Luke’s- psoriatic arthritis (PsA) include the anti–tumor Roosevelt and Beth Israel Medical Centers of the Icahn School of B necrosis factor (TNF) α monoclonal antibodies adali- Medicine at Mount Sinai, New York, New York. 1 Drs. Feely and Smith report no conflict of interest. Dr. Weinberg mumab, etanercept, and infliximab ; however, addi- is an investigator and speaker for AbbVie, Inc; Amgen Inc; and tional TNF-α inhibitors as well as drugs targeting other Novartis Pharmaceutical Corporation. pathways presently are in the pipeline. Novel biologic This article is the second of a 3-part series. The third part will appear treatments currently in phase 2 through phase 4 in July 2015. clinical trials, including those that have recently been Correspondence: Meghan A. Feely, MD, Department of Dermatology, Icahn School of Medicine at Mount Sinai, Mount Sinai St. Luke’s- approved by the US Food and Drug Administration Roosevelt, 1090 Amsterdam Ave, Ste 11B, New York, NY 10025 (FDA), are discussed in this article, and a summary is ([email protected]). provided in Table 1. 282 CUTIS® WWW.CUTIS.COM Copyright Cutis 2015. No part of this publication may be reproduced, stored, or transmitted without the prior written permission of the Publisher. Novel Biologic Therapies for Psoriasis Tumor Necrosis Factor α Inhibitors with moderate to severe psoriasis, clinical benefit Certolizumab Pegol—Certolizumab pegol (CZP; was reported at 12 weeks in 75.9% of participants UCB, Inc), a pegylated TNF-α inhibitor, is unique for Dermatology Life Quality Index, and 64.8% and in that it does not possess a fragment crystalliz- 54.1% for psoriasis- and PsA-related pain scores, able (Fc) region and consequently does not trigger respectively.10 However, ABT-874 was withdrawn by complement activation. The drug is presently FDA the manufacturer as of 2011 due to concerns regard- approved for active PsA, rheumatoid arthritis, and ing adverse cardiovascular events.9 ankylosing spondylitis. One phase 2 study reported BI 655066—BI 655066 (Boehringer Ingelheim psoriasis area severity index (PASI) scores of GmbH) is a human monoclonal antibody that 75 in 83% (48/58) of participants who received targets the p19 subunit of IL-23. A phase 1 study CZP 400 mg at week 0 and every other week of the pharmacokinetics and pharmacodynam- until week 10 (P.001 vs placebo).3 In a 24-week ics of intravenous (IV) versus subcutaneous (SC) phase 3 study (known as RAPID-PsA), 409 par- administration of BI 655066 as well as its safety ticipants were randomized into 3 study arms: and effectiveness versus placebo recently was com- (1) CZP 400 mg every 4 weeks; (2) CZP 200 mg pleted (NCT01577550), but the results were not every 2 weeks; (3) placebo every 2 weeks.4 Of note, available at the time of publication. A phase 2 20% of participants had previously received a study comparing 3 dosing regimens of BI 655066 TNF inhibitor. The study demonstrated improvements versus ustekinumab is ongoing but not actively in participant-reported outcomes with use of CZP recruiting patients at the time of publi- regardless of prior TNF inhibitor use.4 cation (NCT02054481). CHS-0214—CHS-0214 (Coherus BioSciences, Ustekinumab (CNTO 1275)—Ustekinumab Inc) is a TNF-α inhibitor and etanercept (formerly known as CNTO 1275)(Janssen Biotech, biosimilar that has entered into a 48-week mul- Inc) is a humancopy monoclonal antibody that inhibits ticenter phase 3 trial (known as RaPsOdy) for the p40 subunit of IL-12 and IL-23. It was FDA patients with chronic plaque psoriasis. The purpose approved for treatment of moderate to severe plaque of the study is to compare PASI scores for CHS- psoriasis in September 200911 and PsA in 0214 and etanercept to evaluate immunogenicity, Septembernot 2013 12 for adult patients 18 years or older. safety, and effectiveness over a 12-week period.5 One phase 3 trial (known as ACCEPT) compared Comparable pharmacokinetics were established in the effectiveness of ustekinumab versus etanercept in an earlier study.6 903 participants with moderate to severe psoriasis Doat 67 centers worldwide.13 Participants were ran- Inhibition of the IL-12/IL-23 Pathway domly assigned to receive SC injections of either IL-12 and IL-23 are cytokines with prostaglan- 45 mg or 90 mg of ustekinumab (at weeks 0 and 4) din E2–mediated production by dendritic cells that or high-dose etanercept (50 mg twice weekly for share structural (eg, the p40 subunit) and functional 12 weeks). At week 12, PASI 75 was noted in 67.5% similarities (eg, IFN-γ production). However, each of participants who received 45 mg of ustekinumab has distinct characteristics. IL-12 aids in naive CD4 and 73.8% of participants who received 90 mg com- T-cell differentiation, whileCUTIS IL-23 induces IL-17 pared to 56.8% of those who received etanercept production by CD4 memory T cells. IL-17 triggers (P.01 and P.001, respectively). In participants a proinflammatory chemokine cascade and produces who showed no response to etanercept, PASI 75 IL-1, IL-6, nitric oxide synthase 2, and TNF-α.7 was achieved in 48.9% within 12 weeks after cross- Briakinumab (ABT-874)—Briakinumab (for- over to ustekinumab. One or more adverse events merly known as ABT-874)(Abbott Laboratories) (AEs) occurred through week 12 in 66.0% of the is a human monoclonal antibody that inhibits the 45-mg ustekinumab group, 69.2% of the p40 subunit of IL-12 and IL-23. In a phase 3 trial 90-mg group, and 70.0% of the etanercept group; of 350 participants with moderate to severe pso- serious AEs were noted in 1.9%, 1.2%, and riasis, week 12 PASI 75 scores were achieved in 1.2%, respectively.13 A 5-year follow-up study of 80.6% of participants who received briakinumab 3117 participants reported an incidence of AEs versus 39.6% of those who received etanercept and with ustekinumab that was comparable to other 6.9% of those who received placebo.8 In a 52-week biologics, with malignancy and mortality rates phase 3 trial of 317 participants with moderate to comparable to age-matched controls.14 severe psoriasis, PASI 75 scores were observed in In a phase 3, multicenter, double-blind, 81.8% of participants who received briakinumab placebo-controlled trial (know as PSUMMIT I), versus 39.9% of those who received methotrexate.9 615 adults with active PsA who had not previously In another 52-week phase 3 trial of 1465 participants been treated with TNF inhibitors were randomly WWW.CUTIS.COM VOLUME 95, MAY 2015 283 Copyright Cutis 2015. No part of this publication may be reproduced, stored, or transmitted without the prior written permission of the Publisher. Novel Biologic Therapies for Psoriasis Table 1. Novel Biologics for Psoriasis Currently in Development or Recently Approved2,a Mechanism Mode of Stage of Product Manufacturer of Action Indication(s) Delivery Development Certolizumab UCB, Inc Anti–TNF-α Psoriasis, PsA SC Phase 3 pegol CHS-0214 Coherus Anti–TNF-α Psoriasis SC Phase 3 BioSciences, Inc ABT-874 Abbott Anti–IL-12/IL-23 Psoriasis SC Phase 3b (briakinumab) Laboratories monoclonal antibody directed against the p40 subunit BI 655066 Boehringer Anti-inflammatory Psoriasis SC, IV Phase 2 Ingelheim GmbH (IL-23 inhibitor) CNTO 1275 Janssen Biotech, Monoclonal Psoriasis, PsA SC Phase 4 (ustekinumab) Inc antibody to p40 that inhibits binding of IL-12/IL-23 receptors copy CNTO 1959
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