Skyrizi (Risankizumab-rzaa) a New Treatment Option Approved by the FDA for Patients with Moderate-to-Severe Plaque Psoriasis

2019 Payers' Guide Mid-Year Addendum - Select Drug Profiles
Loretta Fala
Medical Writer
More than 8 million people in the United States are affected by psoriasis, a chronic skin disease associated with overactive inflammatory and immune responses.1,2 Approximately 80% to 90% of individuals with psoriasis have plaque psoriasis, the most common form of the disease, which is characterized by thick, raised patches (plaques) that can present anywhere on the skin, but most often appear on the knees, elbows, lower back, and scalp.3,4 In addition, plaque psoriasis is often accompanied by pruritus (severe itching), pain, and, in some cases, bleeding of psoriatic patches.4

Plaque psoriasis imposes a substantial burden on the patient’s physical, social, and psychological well-being.5 Overall, 60% of patients report that psoriasis is very problematic in their everyday life; moderate-to-severe disease inflicts the greatest negative impact on quality of life.1 Furthermore, as many as 35% of people with psoriasis will eventually have psoriatic arthritis.5 In addition, individuals with psoriasis are at an increased risk for depression, cardiovascular disease, type 2 diabetes, kidney disease, metabolic syndrome, and eye disorders.6

Patients with plaque psoriasis may receive treatment with topical agents, phototherapy, conventional systemic therapies (ie, cyclosporine, methotrexate, retinoids) and other systemic therapies, including an oral phosphodiesterase-4 inhibitor, biologic therapies (ie, tumor necrosis factor inhibitors, interleukin [IL]-17 antagonists, IL-23 antagonists, and an IL-12/IL-23 antagonist), and biosimilar agents.7-9

Risankizumab-rzaa FDA Approved for Plaque Psoriasis

On April 23, 2019, risankizumab-rzaa (Skyrizi; AbbVie), an IL-23 antagonist, was approved by the US Food and Drug Administration (FDA) for the treatment of adults with moderate-to-severe plaque psoriasis who are candidates for systemic therapy or phototherapy.10

Commenting on the approval of risankizumab, ­Kenneth B. Gordon, MD, Professor and Chair of Dermatology, Medical College of Wisconsin, and chief inves­tigator for the UltIMMa-1 clinical trial, stated, “The complex nature of psoriasis and the variability or loss of treatment response over time can prevent some patients from achieving their treatment goals.”10 Dr Gordon added, “In clinical trials, risankizumab demonstrated high levels of skin clearance that persisted through one year. I’m pleased the dermatology community now has a new option that can help patients achieve and maintain a high level of treatment response.”10

Mechanism of Action

IL-23 is a naturally occurring cytokine that plays a role in the inflammatory and immune responses that are implicated in the pathogenesis of psoriasis.11

Risankizumab, a humanized immunoglobulin G1 monoclonal antibody, selectively binds to the p19 subunit of human IL-23 cytokine and blocks its interaction with the IL-23 receptor, thereby inhibiting the release of proinflammatory cytokines and chemokines.11

Dosing and Administration

Risankizumab is available for injection as a 75-mg/­0.83-mL solution in a single-dose prefilled syringe.11

The recommended dose of risankizumab is 150 mg (two 75-mg injections) administered by subcutaneous injection at week 0, week 4, and every 12 weeks thereafter. Patients should be evaluated for tuberculosis infection before initiating treatment with risankizumab.11

Pivotal Clinical Trials

UltIMMa-1 and UltIMMa-2

The efficacy and safety of risankizumab were eval­uated in 2 phase 3 clinical trials, UltIMMa-1 and ­UltIMMa-2, double-blind, randomized, placebo-controlled studies that included 997 patients (mean age, 48 years in UltIMMa-1 and 47 years in UltIMMa-2) with moderate-­to-severe plaque psoriasis.12

Patients in both studies received treatment at weeks 0, 4, and every 12 weeks thereafter. In both studies, a significantly greater proportion of patients receiving risankizu­mab achieved a 90% improvement in Psoriasis Area and Severity Index (PASI; PASI 90) and static Physician’s Global Assessment (sPGA) score of 0 or 1 at week 16 compared with patients receiving placebo (Table).11,12

Figure 1

The treatment response with risankizumab was sustained at 1 year.11,12 In the UltIMMa-1 trial, 58% of patients who received treatment with risankizumab achieved an sPGA score of 0, 82% achieved a PASI 90, and 56% achieved a PASI 100 at week 52. In the ­UltIMMa-2 trial, 60% of the patients who received treatment with risankizumab achieved an sPGA score of 0, 81% achieved a PASI 90, and 60% achieved a PASI 100 at week 52.12

Among patients in UltIMMa-1 and UltIMMa-2 who received risankizumab and achieved a PASI 100 at week 16, 80% who continued with risankizumab treatment maintained a PASI 100 at week 52; of those who achieved a PASI 90 at week 16, 88% of patients maintained a PASI 90 at week 52.12

IMMhance

The IMMhance trial was a randomized, double-blind, placebo-controlled, phase 3 clinical trial that included 507 patients (median age, 49.2 years) who were randomized to risankizumab or to placebo at weeks 0, 4, and every 12 weeks thereafter.11,13 At week 16, risan­kizumab demonstrated superior response rates versus placebo in the co-primary efficacy end points of sPGA score of 0 or 1 (84% vs 7%, respectively) and PASI 90 (73% vs 2%, respectively).11,13

Patients who originally received risankizumab and achieved an sPGA score of 0 or 1 at week 28 were rerandomized to continue treatment with risankizumab every 12 weeks or to withdraw from receiving risankizumab. At 52 weeks, 87% of patients rerandomized to continue ­risankizumab achieved an sPGA score of 0 or 1 versus 61% of the patients who were rerandomized to withdraw from risankizumab treatment.11,14

Adverse Events

The most common adverse events (≥1%) associated with risankizumab-rzaa are upper respiratory infections (13%), headache (3.5%), fatigue (2.5%), injection-site reactions (1.5%), and tinea infections (1.1%).11

During the first 16 weeks of treatment, infections were reported in 22.1% of the patients who received risankiz­umab versus 14.7% of the patients who received placebo. Serious infections (in ≤0.4% of patients in the ris­ankizumab and placebo groups) included cellulitis, ­osteomyelitis, sepsis, and herpes zoster.11

The rates of adverse reactions at week 52 were similar to those reported during the first 16 weeks of risankizumab exposure, and no new adverse events were identified. Through week 52, serious infections leading to study discontinuation included pneumonia.11

There are no contraindications for the use of ­risankizumab.11

Drug Interactions

Live vaccines should not be administered during treatment with risankizumab.11

Use in Specific Patient Populations

Data on the use of risankizumab in pregnant women are insufficient to assess the risk for birth defects, miscarriage, or adverse effects for the mother or the fetus. It is possible for risankizumab to be transferred from the mother to the developing fetus.11

Data are not available on the presence or effect of ­risankizumab on the breastfed infant or on the mother’s milk production. The health benefits of breastfeeding should be weighed against the mother’s need for risan­kizumab treatment and any potential adverse effects on the breastfed child from risankizumab treatment or from the mother’s underlying condition.11

The overall number of patients aged ≥65 years was not sufficient to establish whether they respond different from younger patients. Of 2234 patients exposed to ­risankizumab (243 aged ≥65 years and 24 aged ≥75 years), no overall differences were seen in treatment response or safety between the older and younger patients.11

Warnings and Precautions

Risankizumab may increase the risk for infections. Patients should be advised to seek medical advice if the signs or symptoms of infection occur. If the patient has an infection, risankizumab should be discontinued until the infection is resolved.11

Patients should be evaluated for tuberculosis before initiating treatment with risankizumab. For patients with a history of latent or active tuberculosis whose adequate treatment course cannot be confirmed, antituberculosis therapy should be considered before initial treatment with risankizumab. Treatment with risankizumab should not be administered to patients with active tuberculosis.11

Age-appropriate immunizations should be considered before initiating treatment with risankizumab. Live vaccines should not be administered during ­risankizumab treatment.11

Conclusion

The FDA approval of risankizumab-rzaa, an IL-23 antagonist, provides a new treatment option for patients with moderate-to-severe plaque psoriasis who are candidates for systemic therapy or for phototherapy. Treatment with risankizumab demonstrated significant improvements in psoriasis manifestations at 16 weeks, as was shown by the proportion of patients who achieved an sPGA score of 0 or 1, PASI 90, and PASI 100. For the majority of patients who responded to and continued receiving risankizumab, their treatment response was sustained through week 52.

References

  1. National Psoriasis Foundation. Statistics. www.psoriasis.org/content/statistics. Accessed June 24, 2019.
  2. National Psoriasis Foundation. The immune system and psoriasis. www.psoria sis.org/researchers/science-of-psoriasis/immune-system. Accessed June 26, 2019.
  3. American Academy of Dermatology. What is psoriasis? www.aad.org/public/diseases/scaly-skin/psoriasis/what-is-psoriasis. Accessed June 25, 2019.
  4. National Psoriasis Foundation. Psoriasis. February 2015. www.psoriasis.org/sites/default/files/psoriasis_fact_sheet.pdf. Accessed June 26, 2019.
  5. World Health Organization. Global Report on Psoriasis. Geneva, Switzerland: 2016. https://apps.who.int/iris/bitstream/handle/10665/204417/9789241565189_eng.pdf?sequence=1&isAllowed=y. Accessed June 26, 2019.
  6. National Psoriasis Foundation. Comorbidities associated with psoriatic disease. www.psoriasis.org/about-psoriasis/related-conditions. Accessed June 26, 2019.
  7. American Academy of Dermatology. Medications and light treatments for psoriasis. www.aad.org/public/diseases/scaly-skin/psoriasis/diagnosis-and-treatment-of-psoriasis/medications-and-light-treatments. Accessed June 25, 2019.
  8. National Psoriasis Foundation. Psoriasis treatments. www.psoriasis.org/about-psoriasis/treatments. Accessed July 1, 2019.
  9. National Psoriasis Foundation. Treatment comparison. www.psoriasis.org/sites/default/files/treatment_comparison_chart1.pdf. Accessed July 1, 2019.
  10. PRNewswire. FDA approves Skyrizi (risankizumab-rzaa) for moderate to severe plaque psoriasis. April 2019. www.drugs.com/newdrugs/fda-approves-­skyrizi-risankizumab-rzaa-moderate-severe-plaque-psoriasis-4951.html. Accessed June 24, 2019.
  11. Skyrizi (risankizumab-rzaa) injection, for subcutaneous use [prescribing information]. North Chicago, IL: AbbVie; April 2019.
  12. Gordon KB, Strober B, Lebwohl M, et al. Efficacy and safety of risankizu­mab in moderate-to-severe plaque psoriasis (UltIMMa-1 and UltIMMa-2): results from two double-blind, randomised, placebo-controlled and ustekinumab-­controlled phase 3 trials. Lancet. 2018;392:650-661.
  13. ClinicalTrials.gov. BI 655066 / ABBV-066 (risankizumab) in moderate to severe plaque psoriasis with randomized withdrawal and re-treatment (NCT02672852). https://clinicaltrials.gov/ct2/show/NCT02672852. Accessed June 26, 2019.
  14. Langley RG, Blauvelt A, Gooderham M, et al. Efficacy and safety of continuous Q12W risankizumab versus treatment withdrawal: results from the phase 3 IMMhance trial. Poster presented at the American Academy of Dermatology annual meeting; March 1-5, 2019; Washington, DC.
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