Aetna Commercial Clinical Policy

Aetna Tildrakizumab-asmn (Ilumya) [Medicare] Form

Effective Date

12/16/2022

Last Reviewed

08/22/2023

Original Document

  Reference



Background for this Policy

U.S. Food and Drug Administration (FDA)-Approved Indications

Treatment of adult patients with moderate-to-severe plaque psoriasis (PsO) who are candidates for systemic therapy or phototherapy

Tildrakizumab-asmn is available as Ilumya (Sun Pharmaceutical Industries, Inc). Tildrakizumab is humanized IgG1/k monoclonal antibody that selectively binds to the p19 subunit of IL-23 and inhibits its interaction with the IL-23 receptor.

Labeled warnings and precautions include hypersensitivity and infections. Cases of angioedema and urticaria occurred in Ilumya treated subjects in clinical trials. Ilumya may increase the risk of infection. Although infections were slightly more common in the Ilumya group (23%), the difference in frequency of infections between the Ilumya group and the placebo group was less than 1% during the placebo-controlled period. However, subjects with active infections or a history of recurrent infections were not included in clinical trials. Upper respiratory infections occurred more frequently in the Ilumya group than in the placebo group. The rates of serious infections for the Ilumya group and the placebo group were less than or equal to 0.3% (Sun Pharmaceutical Industries, 2022).

The most common (1% or more) adverse reactions associated with Ilumya treatment are upper respiratory infections, injection site reactions, and diarrhea.

Plaque Psoriasis

In March 2018, the FDA approved tildrakizumab (Ilumya) for the treatment of adults with moderate-to-severe plaque psoriasis who are candidates for systemic therapy or phototherapy.

Reich et al (2017) conducted two three-part, parallel group, double-blind, randomised controlled studies, reSURFACE 1 (at 118 sites in Australia, Canada, Japan, the UK, and the USA) and reSURFACE 2 (at 132 sites in Europe, Israel, and the USA). Participants aged 18 years or older with moderate-to-severe chronic plaque psoriasis (body surface area involvement ≥10%, Physician's Global Assessment [PGA] score ≥3, and Psoriasis Area and Severity Index [PASI] score ≥12) were randomised (via interactive voice and web response system) to tildrakizumab 200 mg, tildrakizumab 100 mg, or placebo in reSURFACE 1 (2:2:1), or to tildrakizumab 200 mg, tildrakizumab 100 mg, placebo, or etanercept 50 mg (2:2:1:2). Randomisation was done by region and stratified for bodyweight (≤90 kg or >90 kg) and previous exposure to biologics therapy for psoriasis. Investigators, participants, and study personnel were blinded to group allocation and remained blinded until completion of the studies. Assigned medication was identical in appearance and packaging. Tildrakizumab was administered subcutaneously at weeks 0 and 4 during part 1 and at week 16 during part 2 (weeks 12 and 16 for participants re-randomised from placebo to tildrakizumab; etanercept was given twice weekly in part 1 of reSURFACE 2 and once weekly during part 2). The co-primary endpoints were the proportion of patients achieving PASI 75 and PGA response (score of 0 or 1 with ≥2 grade score reduction from baseline) at week 12. Safety was assessed in the all-participants-as-treated population, and efficacy in the full-analysis set. These trials are registered with ClinicalTrials.gov, numbers NCT01722331 (reSURFACE 1) and NCT01729754 (reSURFACE 2). These studies are completed, but extension studies are ongoing. The reSURFACE 1 trial ran from Dec 10, 2012, to Oct 28, 2015. The reSURFACE 2 trial ran from Feb 12, 2013, to Sept 28, 2015. In reSURFACE 1, 772 patients were randomly assigned, 308 to tildrakizumab 200 mg, 309 to tildrakizumab 100 mg, and 155 to placebo. At week 12, 192 patients (62%) in the 200 mg group and 197 patients (64%) in the 100 mg group achieved PASI 75, compared with 9 patients (6%) in the placebo group (p<0·0001 for comparisons of both tildrakizumab groups vs placebo). 182 patients (59%) in the 200 mg group and 179 patients (58%) in the 100 mg group achieved PGA responses, compared with 11 patients (7%) in the placebo group (p<0·0001 for comparisons of both tildrakizumab groups vs placebo). In reSURFACE 2, 1090 patients were randomly assigned, 314 to tildrakizumab 200 mg, 307 to tildrakizumab 100 mg, 156 to placebo, and 313 to etanercept. At week 12, 206 patients (66%) in the 200 mg group, and 188 patients (61%) in the 100 mg group achieved PASI 75, compared with 9 patients (6%) in the placebo group and 151 patients (48%) in the etanercept group (p<0·0001 for comparisons of both tildrakizumab groups vs placebo; p<0·0001 for 200 mg vs etanercept and p=0·0010 for 100 mg vs etanercept). 186 patients (59%) in the 200 mg group, and 168 patients (59%) [corrected] in the 100 mg group achieved a PGA response, compared with 7 patients (4%) in the placebo group and 149 patients (48%) in the etanercept group (p<0·0001 for comparisons of both tildrakizumab groups vs placebo; p=0·0031 for 200 mg vs etanercept and p=0·0663 for 100 mg vs etanercept). Serious adverse events were similar and low in all groups in both trials. One patient died in reSURFACE 2, in the tildrakizumab 100 mg group; the patient had alcoholic cardiomyopathy and steatohepatitis, and adjudication was unable to determine the cause of death. The authors concluded that in the two phase 3 trials, tildrakizumab 200 mg and 100 mg were efficacious compared with placebo and etanercept and were well tolerated in the treatment of patients with moderate-to-severe chronic plaque psoriasis.

Appendix

Examples of Clinical Reasons to Avoid Pharmacologic Treatment with Methotrexate, Cyclosporine or Acitretin

  • Clinical diagnosis of alcohol use disorder, alcoholic liver disease or other chronic liver disease
  • Drug interaction
  • Risk of treatment-related toxicity
  • Pregnancy or currently planning pregnancy
  • Breastfeeding
  • Significant comorbidity prohibits use of systemic agents (examples include liver or kidney disease, blood dyscrasias, uncontrolled hypertension)
  • Hypersensitivity
  • History of intolerance or adverse event
    • Note

    : Requires Precertification:

    Precertification of tildrakizumab-asmn (Ilumya) is required of all Aetna participating providers and members in applicable plan designs. For precertification of Ilumya, call (866) 752-7021 (commercial), or fax (888) 267-3277. For Statement of Medical Necessity (SMN) precertification forms, see

    Specialty Pharmacy Precertification .

    For Medicare Part B plans, call (866) 503-0857, or fax (844) 268-7263.

    Prescribing Specialties

  • This medication must be prescribed by or in consultation with a dermatologist.

    • Criteria for Initial Approval

    Aetna considers tildrakizumab-asmn (Ilumya) medically necessary for plaque psoriasis (PsO) where the member has a documented negati

    ve tuberculosis (TB) test

    (which can include a tuberculosis skin test (PPD), an interferon-release assay (IGRA), or a chest x-ray) Footnote1 * within 6 months of initiating therapy for persons who are naïve to biologic drugs or targeted synthetic drugs associated with an increased risk of TB:
  • For adult members who have previously received a biologic or targeted synthetic drug (e.g., Sotyktu, Otezla) indicated for the treatment of moderate to severe plaque psoriasis;
    • or
  • For adult members for treatment of moderate-to-severe plaque psoriasis when
    • any
  • of the following criteria is met:
  • Crucial body areas (e.g., hands, feet, face, neck, scalp, genitals/groin, intertriginous areas) are affected;
    • or
  • At least 10% of the body surface area (BSA) is affected;
    • or
  • At least 3% of BSA is affected and the member meets
    • any
  • of the following criteria:
  • Member has had an inadequate response or intolerance to either phototherapy (e.g., UVB, PUVA) or pharmacologic treatment with methotrexate, cyclosporine, or acitretin;
    • or
  • Member has a clinical reason to avoid pharmacologic treatment with methotrexate, cyclosporine, and acitretin (see
    • Appendix
  • ).

    • Aetna considers all other indications as experimental and investigational (for additional information, see Experimental and Investigational and Background sections).

    Continuation of Therapy

    Aetna considers continuation of

    tildrakizumab-asmn (Ilumya) therapy medically necessary for all adult members (including new members) who are using the requested medication for moderate to severe plaque psoriasis and who achieve or maintain a positive clinical response as evidenced by low disease activity or improvement in signs and symptoms of the condition when any of the following is met:
  • Reduction in body surface area (BSA) affected from baseline;
    • or
  • Improvement in signs and symptoms from baseline (e.g., itching, redness, flaking, scaling, burning, cracking, pain).
    • Footnote1

    * If the screening test for TB is positive, there must be further testing to confirm there is no active disease. Do not administer the requested medication to members with active TB infection. If there is latent disease, TB treatment must be started before initiation of the requested medication.