FDA LABELED INDICATIONS AND DOSAGE
Agent(s) |
FDA Indication(s) |
Notes |
Ref# |
Rhapsido® (remibrutinib) Tablet |
Treatment of chronic spontaneous urticaria (CSU) in adult patients who remain symptomatic despite H1 antihistamine treatment Limitation of Use: Not indicated for other forms of urticaria |
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1 |
This policy is designed to address medical guidelines that are appropriate for the majority of individuals with a particular disease, illness, or condition. Each person's unique clinical circumstances may warrant individual consideration, based on review of applicable medical records.
PRIOR AUTHORIZATION CLINICAL CRITERIA FOR APPROVAL
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Module |
Clinical Criteria for Approval |
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PA |
Initial Evaluation Target Agent(s) will be approved when ALL of the following are met: 1. ONE of the following: A. The requested agent is eligible for continuation of therapy AND ONE of the following:
1. The patient has been treated with the requested agent (starting on samples is not approvable) within the past 90 days OR 2. The prescriber states the patient has been treated with the requested agent (starting on samples is not approvable) within the past 90 days AND is at risk if therapy is changed OR B. BOTH of the following: 1. ONE of the following: A. The patient has a diagnosis of chronic spontaneous urticaria (CSU) (otherwise known as chronic idiopathic urticaria [CIU]) AND ALL of the following: 1. The patient has had hives and itching for more than 6 weeks AND 2. The prescriber has evaluated the patient to determine if the patient is currently treated with medication known to cause or worsen urticaria (e.g., NSAIDs) in order to reduce urticaria risk AND 3. The patient has ONE of the following: A. Tried and had an inadequate response to the FDA labeled maximum dose of ONE second-generation H1-antihistamine (e.g., cetirizine, desloratadine, fexofenadine, levocetirizine, loratadine) AND ONE of the following: 1. The patient has tried and had an inadequate response to a maximally tolerated dose of ONE second-generation H1-antihistamine titrated up to 4 times above the FDA labeled maximum dose after at least a 2-week duration of therapy OR 2. There is support that the patient cannot be treated with a second-generation H1-antihistamine at a dose above the FDA labeled maximum dose OR B. An intolerance or hypersensitivity to ONE second-generation H1-antihistamine OR C. An FDA labeled contraindication to ALL second-generation H1-antihistamines OR B. The patient has another FDA labeled indication for the requested agent and route of administration AND 2. If the patient has an FDA labeled indication, then ONE of the following: A. The patient’s age is within FDA labeling for the requested indication for the requested agent OR B. There is support for using the requested agent for the patient’s age for the requested indication OR C. The patient has another indication that is supported in compendia for the requested agent and route of administration AND 2. If the patient has a diagnosis of chronic spontaneous urticaria (CSU) (otherwise known as chronic idiopathic urticaria [CIU]), then ONE of the following: A. BOTH of the following: 1. The patient is currently treated with second-generation H1-antihistamine therapy (e.g., cetirizine, desloratadine, fexofenadine, levocetirizine, loratadine) AND 2. The patient will continue second-generation H1-antihistamine therapy in combination with the requested agent OR B. The patient has an intolerance, hypersensitivity, or FDA labeled contraindication to ALL second-generation H1-antihistamines AND 3. The prescriber is a specialist in the area of the patient’s diagnosis (e.g., dermatologist, allergist, immunologist), or the prescriber has consulted with a specialist in the area of the patient’s diagnosis AND 4. ONE of the following (please refer to “Agents NOT to be used Concomitantly” table): A. The patient will NOT be using the requested agent in combination with another immunomodulatory agent (e.g., TNF inhibitors, JAK inhibitors, IL-4 inhibitors) OR B. The patient will be using the requested agent in combination with another immunomodulatory agent AND BOTH of the following: 1. The prescribing information for the requested agent does NOT limit the use with another immunomodulatory agent AND 2. There is support for the use of combination therapy (submitted copy of clinical trials, phase III studies, or guidelines required) AND 5. The patient does NOT have any FDA labeled contraindications to the requested agent Compendia Allowed: AHFS, DrugDex 1 or 2a level of evidence, or NCCN 1 or 2a recommended use Length of Approval: 12 months NOTE: If Quantity Limit applies, please refer to Quantity Limit Criteria.
Renewal Evaluation Target Agent(s) will be approved when ALL of the following are met: 1. The patient has been previously approved for the requested agent through the plan’s Prior Authorization process (Note: patients not previously approved for the requested agent will require initial evaluation review) AND 2. The patient has had clinical benefit with the requested agent AND 3. If the patient has a diagnosis of chronic spontaneous urticaria (CSU) (otherwise known as chronic idiopathic urticaria [CIU]), then ONE of the following: A. The patient will continue second-generation H1-antihistamine therapy (e.g., cetirizine, desloratadine, fexofenadine, levocetirizine, loratadine) in combination with the requested agent OR B. The patient has an intolerance, hypersensitivity, or FDA labeled contraindication to ALL second-generation H1-antihistamines AND 4. The prescriber is a specialist in the area of the patient’s diagnosis (e.g., dermatologist, allergist, immunologist), or the prescriber has consulted with a specialist in the area of the patient’s diagnosis AND 5. ONE of the following (please refer to “Agents NOT to be used Concomitantly” table): A. The patient will NOT be using the requested agent in combination with another immunomodulatory agent (e.g., TNF inhibitors, JAK inhibitors, IL-4 inhibitors) OR B. The patient will be using the requested agent in combination with another immunomodulatory agent AND BOTH of the following: 1. The prescribing information for the requested agent does NOT limit the use with another immunomodulatory agent AND 2. There is support for the use of combination therapy (submitted copy of clinical trials, phase III studies, or guidelines required) AND 6. The patient does NOT have any FDA labeled contraindications to the requested agent Length of Approval: 12 months NOTE: If Quantity Limit applies, please refer to Quantity Limit Criteria. |
PRIOR AUTHORIZATION CLINICAL CRITERIA OPERATIONAL LEVEL OF EVIDENCE REQUIREMENTS
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Module |
Ops Set Up |
Validation Options |
Other Explanation |
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PA |
Documentation: Requirements as noted within the policy;Validation: Apply Baseline and go to Validation Options |
Age Verification;Continuation of Therapy;Contraindication, intolerance, hypersensitivity;Diagnosis;Other (see Other explanation field);Required Concomitant Therapy |
*Collect info from prescriber to review: Support that the patient cannot be treated with a second-generation H1-antihistamine at a dose above the FDA labeled maximum dose
*Review the requested agent's prescribing information: The prescribing information for the requested agent does NOT limit the use with another immunomodulatory agents |
QUANTITY LIMIT CLINICAL CRITERIA FOR APPROVAL
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Module |
Clinical Criteria for Approval |
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Universal QL |
Quantity Limit for the Target Agent(s) will be approved when ONE of the following is met: 1. The requested quantity (dose) does NOT exceed the program quantity limit OR 2. The requested quantity (dose) exceeds the program quantity limit AND ONE of the following: A. BOTH of the following: 1. The requested agent does NOT have a maximum FDA labeled dose for the requested indication AND 2. There is support for therapy with a higher dose for the requested indication OR B. BOTH of the following: 1. The requested quantity (dose) does NOT exceed the maximum FDA labeled dose for the requested indication AND 2. There is support for why the requested quantity (dose) cannot be achieved with a lower quantity of a higher strength that does NOT exceed the program quantity limit OR C. BOTH of the following: 1. The requested quantity (dose) exceeds the maximum FDA labeled dose for the requested indication AND 2. There is support for therapy with a higher dose for the requested indication Length of Approval: up to 12 months |
QUANTITY LIMIT CLINICAL CRITERIA OPERATIONAL LEVEL OF EVIDENCE REQUIREMENTS
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Module |
Ops Set Up |
Validation Options |
Other Explanation |
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Universal QL |
Validation: Apply Baseline and go to Validation Options |
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CONTRAINDICATION AGENTS
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Contraindicated as Concomitant Therapy |
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Agents NOT to be used Concomitantly Abrilada
(adalimumab-afzb) |
Chronic Spontaneous Urticaria (CSU) |
Chronic spontaneous urticaria (CSU), also referred to as chronic urticaria (CU) or chronic idiopathic urticaria (CIU), is a mast cell-mediated condition that involves the recurrent spontaneous occurrence of urticaria and/or angioedema.(2) Urticaria is characterized by the development of wheals (hives), angioedema, or both. CSU is defined by the presence of urticaria for more than 6 weeks with no definite eliciting factor involved. Signs and symptoms may occur daily or follow an intermittent/recurrent course.(3) Routine diagnostic tests (e.g., blood tests for complete blood count and inflammatory markers, skin prick test) are mainly used to rule out other potential diseases and not to confirm the diagnosis.(2) Medication that is suspected to worsen the disease (e.g., NSAIDs) should be discontinued or substituted by another class of agents to reduce disease exacerbations. CSU can be a debilitating condition that significantly impairs a patient's quality of life, and treatment goals include symptom control and normalization of quality of life for the patient.(3) The international European Academy of Allergy and Clinical Immunology (EAACI)/Global Allergy and Asthma European Network (GA2LEN)/European Dermatology Forum (EDF)/Asia Pacific Association of Allergy, Asthma and Clinical Immunology (APAAACI) guideline recommends the following algorithm for the treatment of CSU:(3)
High dose second-generation H1-antihistamine therapy has been suggested in guidelines since the year 2000, and no serious adverse events or side effects from long-term use or potential accumulation have been reported. Treatment for CSU should be evaluated every 3 to 6 months to assess disease activity, impact, and control. The severity of urticaria can fluctuate, including the possibility of spontaneous remission. In addition, patients should be assessed for any side effects of treatment. If an adjustment to treatment is warranted, it may include stepping up therapy, changing medication due to side effects, or stepping down treatment if the patient has been symptom free for 3 to 6 months.(3) Omalizumab was approved for the treatment of CSU in 2014 and has since received placement in treatment guidelines. However, for some patients omalizumab provides partial or no improvement in their signs and symptoms.(4) Current guidelines support using cyclosporine as add-on therapy for patients with severe disease and an incomplete response to omalizumab and an antihistamine used in combination, but it is not recommended as standard treatment due to the risk and incidence of adverse effects.(3) Dupilumab has been shown to be an effective treatment for CSU per the LIBERTY CUPID CSU studies, but its place in treatment guidelines has yet to be established. The LIBERTY CSU CUPID-B trial was designed to determine if dupilumab is an effective alternative in patients with a lack of response to omalizumab, incomplete control of their CSU while taking omalizumab, or an inability to tolerate the use of omalizumab. The dupilumab group in this study did not meet statistical significance for reduction in the primary endpoint of change from baseline in itch severity score over 7 days (ISS7) at Week 24.(4) |
Efficacy |
The efficacy of Rhapsido for chronic spontaneous urticaria (CSU) in adult patients who remain symptomatic despite H1 antihistamine treatment was evaluated in two identical, 52-week, multi-center, randomized, double-blind, placebo-controlled clinical trials (REMIX-1 [NCT05030311] and REMIX-2 [NCT05032157]). REMIX-1 and REMIX-2 enrolled a total of 925 adult patients, diagnosed with CSU inadequately controlled despite treatment with H1 antihistamines, as defined by the presence of itch and hives for at least 6 consecutive weeks. All patients were required to have a weekly urticaria activity score (UAS7) of greater than or equal to 16 (range 0-42), a weekly itch severity score (ISS7) of greater than or equal to 6 (range 0-21) and a weekly hives severity score (HSS7) of greater than or equal to 6 (range 0-21) for 7 days prior to randomization. In REMIX-1 and REMIX-2, 32% and 31% of patients had previous exposure to an anti-IgE biologic (e.g., omalizumab), respectively. Patients were randomized in a 2:1 ratio to receive either Rhapsido 25 mg or placebo, in addition to background therapy with an H1 antihistamine, orally twice daily for 24 weeks during the double-blind treatment period and subsequently continued in a 28-week open-label treatment period, during which all patients received Rhapsido 25 mg twice daily. While REMIX-1 and REMIX-2 clinical trials included an open-label period, efficacy is based on results from 912 patients treated during the controlled period of 24 weeks.(1) The co-primary endpoints were absolute change from baseline in ISS7 and HSS7 at Week 12. The ISS7 (range 0 to 21) was defined as the sum of the daily itch severity scores (range 0 to 3) recorded over a 7-day period. The HSS7 (range 0 to 21) was defined as the sum of the daily hive severity scores (range 0 to 3) recorded over a 7-day period. In both REMIX-1 and REMIX-2 studies, the co-primary endpoints showed statistically significant improvement in itch and hives symptoms in patients treated with Rhapsido compared to patients treated with placebo. Improvements in ISS7 and HSS7 at Week 12 were consistent regardless of patients’ baseline total IgE level.(1) |
Safety |
Rhapsido has no FDA labeled contraindications for use.(1) |
Number |
Reference |
1 |
Rhapsido prescribing information. Novartis Pharmaceuticals Corporation. September 2025. |
2 |
Dabija D, Tadi P, Danosos GN. Chronic Urticaria. [Updated 2023 Apr 17]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK555910/ |
3 |
Zuberbier, T, Abdul Latiff, AH, Abuzakouk, M, et al. The international EAACI/GA^2LEN/EuroGuiDerm/APAAACI guideline for the definition, classification, diagnosis, and management of urticaria. Allergy. 2022;77(3):734-766. doi:10.1111/all.15090 |
4 |
Mathur SK, Rosenberg DL, Viswanathan RK. Dupilumab for chronic spontaneous urticaria-marvelous or meek? Journal of Allergy and Clinical Immunology. 2024;154(1):91-93. doi:10.1016/j.jaci.2024.05.004 |
POLICY AGENT SUMMARY PRIOR AUTHORIZATION
Final Module |
Target Agent GPI |
Target Brand Agent(s) |
Target Generic Agent(s) |
Strength |
Targeted MSC |
Targeted NDCs When Exclusions Exist |
Final Age Limit |
Preferred Status |
Effective Date |
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993937650003 |
Rhapsido |
remibrutinib tab |
25 MG |
M ; N ; O ; Y |
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POLICY AGENT SUMMARY QUANTITY LIMIT
Target Agent GPI |
Target Brand Name(s) |
Target Generic Name(s) |
Strength |
QL Amount |
Dose Form |
Days Supply |
Duration |
Targeted NDCs When Exclusions Exist |
Age Limit |
Effective Date |
Term Date |
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99393765000320 |
Rhapsido |
remibrutinib tab |
25 MG |
60 |
Tablets |
30 |
DAYS |
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CLIENT SUMMARY – PRIOR AUTHORIZATION
Target Brand Agent(s) |
Target Generic Agent(s) |
Strength |
Client Formulary |
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Rhapsido |
remibrutinib tab |
25 MG |
Commercial ; HIM ; WY NetR-Commercial Custom |
Target Brand Agent Name(s) |
Target Generic Agent Name(s) |
Strength |
Client Formulary |
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Rhapsido |
remibrutinib tab |
25 MG |
Commercial ; HIM ; WY NetR-Commercial Custom |
