Tildrakizumab-asmn (Ilumya)

Number: 1012

Table Of Contents

Policy
Applicable CPT / HCPCS / ICD-10 Codes
Background
References

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Policy

Scope of Policy

This Clinical Policy Bulletin addresses tildrakizumab-asmn (Ilumya) for commercial medical plans. For Medicare criteria, see Medicare Part B Criteria.

Note: Requires Precertification:

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

1. Prescribing Specialties

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

2. Criteria for Initial Approval

   Aetna considers tildrakizumab-asmn (Ilumya) medically necessary for plaque psoriasis (PsO) when criteria are met: 

   1. 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
   2. For adult members for treatment of moderate to severe plaque psoriasis when any of the following criteria is met:
      
      
      1. Crucial body areas (e.g., hands, feet, face, neck, scalp, genitals/groin, intertriginous areas) are affected; or
      2. At least 10% of the body surface area (BSA) is affected; or
      3. At least 3% of BSA is affected and the member meets any of the following criteria:
         
         
         1. Member has had an inadequate response or intolerance to either phototherapy (e.g., UVB, PUVA) or pharmacologic treatment with methotrexate, cyclosporine, or acitretin; or
         2. Member has a clinical reason to avoid pharmacologic treatment with methotrexate, cyclosporine, and acitretin (see Appendix).

   Aetna considers all other indications as experimental, investigational, or unproven.  

3. 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 either of the following is met:

   1. Reduction in body surface area (BSA) affected from baseline; or
   2. Improvement in signs and symptoms from baseline (e.g., itching, redness, flaking, scaling, burning, cracking, pain).

4. Other

   For all indications: Member has been evaluated for tuberculosis (TB) infection prior to initiation of treatment with a biologic or targeted synthetic drug associated with an increased risk of TB.

   For all indications: Member cannot use the requested medication concomitantly with any other biologic drug or targeted synthetic drug for the same indication.

5. Related Policies

   1. CPB 0205 - Phototherapy and Photochemotherapy (PUVA) for Skin Conditions
   2. CPB 0315 - Etanercept
   3. CPB 0341 - Infliximab
   4. CPB 0577 - Laser Treatment for Psoriasis and Other Selected Skin Conditions
   5. CPB 0655 - Adalimumab
   6. CPB 0720 - Abatacept (Orencia)
   7. CPB 0761 - Certolizumab Pegol (Cimzia)
   8. CPB 0790 - Golimumab (Simponi and Simponi Aria)
   9. CPB 0905 - Secukinumab (Cosentyx)
   10. CPB 0912 - Ustekinumab
   11. CPB 1009 - Risankizumab-rzaa (Skyrizi)
   12. CPB 1011 - Guselkumab (Tremfya)

Dosage and Administration

Note: Approvals may be subject to dosing limits in accordance with FDA-approved labeling, accepted compendia, and/or evidence-based practice guidelines. See Medical Specialty Medication Quantity Limits for more information. Below includes dosing recommendations as per the FDA-approved prescribing information.

Tildrakizumab-asmn is available as Ilumya for subcutaneous injection and supplied as 100 mg/mL solution in a single-dose prefilled syringe. 

Ilumya should only be administered by a healthcare provider.

Plaque psoriasis: The recommended dose is 100 mg at Weeks 0, 4, and every 12 weeks thereafter.

Source: Sun Pharmaceutical Industries, 2025

Experimental, Investigational, or Unproven

Aetna considers concomitant use of tildrakizumab-asmn with any other biologic drug (e.g., adalimumab, anakinra, etanercept, infliximab, rilonacept, tocilizumab) or targeted synthetic drug (e.g. tofacitinib) experimental, investigational, or unproven for the same indication because the effectiveness of this approach has not been established.

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Table:

CPT Codes / HCPCS Codes / ICD-10 Codes

Code	Code Description
Other CPT codes related to the CPB:
71045 - 71048	Radiologic examination, chest
86480	Tuberculosis test, cell mediated immunity antigen response measurement; gamma interferon
86481	enumeration of gamma interferon - producing T cells in cell suspension
86580	Skin test; tuberculosis, intradermal
96372	Therapeutic, prophylactic, or diagnostic injection (specify substance or drug); subcutaneous or intramuscular
96910	Photochemotherapy; tar and ultraviolet B (Goeckerman treatment) or petrolatum and ultraviolet B
96912	psoralens and ultraviolet A (PUVA)
96913	Photochemotherapy (Goeckerman and/or PUVA) for severe photoresponsive dermatoses requiring at least 4-8 hours of care under direct supervision of the physician (includes application of medication and dressings)
HCPCS codes covered if selection criteria are met:
J3245	Injection, tildrakizumab, 1 mg
Other HCPCS codes related to the CPB:
Sotyktu, Otezla -no specific code
J0139	Injection, adalimumab, 1 mg
J1438	Injection, etanercept, 25 mg
J1745	Injection infliximab, 10 mg
J3262	Injection, tocilizumab, 1 mg
J7502	Cyclosporine, oral, 100 mg
J7515	Cyclosporine, oral, 25 mg
J7516	Cyclosporine, parenteral, 250 mg
J8610	Methotrexate, oral, 2.5 mg
J8611	Methotrexate (jylamvo), oral, 2.5 mg
J8612	Methotrexate (xatmep), oral, 2.5 mg
J9250	Methotrexate sodium, 5 mg
J9255	Injection, methotrexate (accord) not therapeutically equivalent to j9250 or j9260, 50 mg
J9260	Methotrexate sodium, 50 mg
Q5103	Injection, infliximab-hyphendyyb, biosimilar, (inflectra), 10 mg
Q5104	Injection, infliximab-hyphenabda, biosimilar, (renflexis), 10 mg
Q5109	Injection, infliximab-qbtx, biosimilar, (ixifi), 10 mg
Q5121	Injection, infliximab-hyphenaxxq, biosimilar, (avsola), 10 mg
Q5133	Injection, tocilizumab-bavi (tofidence), biosimilar, 1 mg
Q5135	Injection, tocilizumab-aazg (tyenne), biosimilar, 1 mg
Q5140	Injection, adalimumab-fkjp, biosimilar, 1 mg
Q5141	Injection, adalimumab-aaty, biosimilar, 1 mg
Q5142	Injection, adalimumab-ryvk biosimilar, 1 mg
Q5143	Injection, adalimumab-adbm, biosimilar, 1 mg
Q5144	Injection, adalimumab-aacf (idacio), biosimilar, 1 mg
Q5145	Injection, adalimumab-afzb (abrilada), biosimilar, 1 mg
ICD-10 codes covered if selection criteria are met:
L40.0 - L40.9	Psoriasis

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Background

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%.

Tuberculosis (TB) infection should be evaluated prior to initiating treatment with Ilumya. Moreover, treatment of latent TB should be initiated prior to Ilumya administration. In clinical trials, of 55 individuals with latent TB who were concurrently treated with Ilumya and appropriate TB prophylaxis, no individual developed active TB (during the mean follow-up of 56.5 weeks). One other individual developed TB while receiving Ilumya. Anti-TB therapy should be considered prior to initiation of Ilumya in patients with a past history of latent or active TB in whom an adequate course of treatment cannot be confirmed. Ilumya should not be administered to patients with active TB infection.

The most common adverse reactions (1% or more) 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, randomized 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 randomized (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). Randomization 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.

Sofen and colleagues (2024) report on Week 52 results from a phase 3b, randomized, double-blind, placebo-controlled trial (NCT03897088) evaluating the safety and efficacy of maintenance tildrakizumab for the treatment of moderate-to-severe plaque psoriasis of the scalp. Patients (n=89; modified intention-to-treat [mITT]) randomized to tildrakizumab continued receiving tildrakizumab 100 mg every 12 weeks. Patients (n=82; mITT) randomized to placebo (analyzed separately) switched to tildrakizumab 100 mg at week 16. Efficacy endpoints included Investigator Global Assessment modified 2011 (scalp) score of 0 or 1 with ≥ 2-grade improvement and ≥ 90% improvement in Psoriasis Scalp Severity Index score from baseline. Safety was assessed from adverse events. The authors found that in patients originally randomized to tildrakizumab versus placebo, Investigator Global Assessment modified 2011 (scalp) and ≥90% improvement in Psoriasis Scalp Severity Index score response rates, respectively, improved from 49.4% versus 7.3% and 60.7% versus 4.9% at week 16 to 62.9% versus 56.1% and 65.2% versus 57.3% at week 52; >80% of week 16 responders to tildrakizumab maintained response. Moreover, no treatment-related serious adverse events occurred. The authors acknowledged that results were obtained under controlled clinical conditions, considered a limitation of the study. The authors concluded that the safety and efficacy of tildrakizumab for the treatment of scalp psoriasis are sustained long-term.

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Appendix

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

1. Clinical diagnosis of alcohol use disorder, alcoholic liver disease or other chronic liver disease
2. Drug interaction
3. Risk of treatment-related toxicity
4. Pregnancy or currently planning pregnancy
5. Breastfeeding
6. Significant comorbidity prohibits use of systemic agents (e.g., liver or kidney disease, blood dyscrasias, uncontrolled hypertension)
7. Hypersensitivity
8. History of intolerance or adverse event

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References