Instructions for oscar models including: CG064, Ver. 5, CG064 Concomitant Concurrent Biologics, CG064, Concomitant Concurrent Biologics, Concurrent Biologics, Biologics

CG064 Concomitant use of Biologics and tsDMARDs

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Clinical Guideline
Oscar Clinical Guideline: Concomitant (Concurrent) use of Biologics (Biologic Response Modifiers Therapies) and targeted synthetic Disease-Modifying Antirheumatic Drugs (tsDMARDs) (CG064, Ver. 5)
Concomitant (Concurrent) use of Biologics (Biologic Response Modifiers Therapies) and targeted synthetic Disease-Modifying Antirheumatic Drugs (tsDMARDs)
Disclaimer Clinical guidelines are developed and adopted to establish evidence-based clinical criteria for utilization management decisions. Clinical guidelines are applicable according to policy and plan type. The Plan may delegate utilization management decisions of certain services to third parties who may develop and adopt their own clinical criteria.
Coverage of services is subject to the terms, conditions, and limitations of a member's policy, as well as applicable state and federal law. Clinical guidelines are also subject to in-force criteria such as the Centers for Medicare & Medicaid Services (CMS) national coverage determination (NCD) or local coverage determination (LCD) for Medicare Advantage plans. Please refer to the member's policy documents (e.g., Certificate/Evidence of Coverage, Schedule of Benefits, Plan Formulary) or contact the Plan to confirm coverage.
Summary Biologic response modifier therapies, or biologics, are specialized agents bioengineered to interact with specific aspects of the immune system. These unique therapeutics modulate the immune response and disrupt inflammation, playing a pivotal role in managing autoimmune diseases. Biologics, also recognized as immunomodulators and anticytokine agents, have a broad treatment scope encompassing conditions like axial ankylosing spondylitis, graft-versus-host disease, juvenile idiopathic arthritis, rheumatoid arthritis, psoriatic arthritis, psoriasis, and inflammatory bowel disease. Beyond autoimmune disorders, biologics also find usage in oncology, where they can target specific cancer cells or mitigate side effects of other cancer therapies. The administration routes for these drugs include intravenous, subcutaneous, and in some instances, oral delivery.
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Classifications of biologics include soluble receptor antagonists, monoclonal antibodies, and cell surface receptor antagonist proteins, defined by their origin and function. Further subclassifications exist based on the mechanism of action and targeted therapy area, such as anti-integrin antibodies, B-cell inhibitors, Interleukin (IL) inhibitors, T-cell inhibitors, and Tumor Necrosis Factor (TNF) inhibitors.
Table 1: Disease-modifying antirheumatic drugs (DMARDs)

Type of DMARD Conventional synthetic DMARDs
Biologic DMARDs

Generic name Azathioprine Hydroxychloroquine Leflunomide Methotrexate Sulfasalazine Abatacept
Adalimumab

Example brand name(s)
Imuran, Azasan
Plaquenil
Arava
Rheumatrex, Trexall, Otrexup, Rasuvo
Azulfidine, Azulfidine EN tabs
Orencia
Abrilada, Amjevita, Cyltezo, Hadlima, Hulio, Humira, Hyrimoz, Idacio, Simlandi, Yuflyma, Yusimry

Administration method Oral Oral Oral Oral or subcutaneous injection Oral Subcutaneous injection or intravenous infusion
Subcutaneous injection

Anakinra

Kineret

Subcutaneous injection

Belimumab

Benlysta

Subcutaneous injection or intravenous infusion

Brodalumab

Siliq

Subcutaneous injection

Canakinumab

Ilaris

Subcutaneous injection

Certolizumab pegol Cimzia

Subcutaneous injection

Etanercept

Enbrel

Subcutaneous injection

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Golimumab Guselkumab Infliximab

Ixekizumab

Mirikizumab

Natalizumab Obinutuzumab

Ofatumumab Risankizumab

Rituximab Sarilumab Secukinumab

Tocilizumab

Ustekinumab

Targeted synthetic DMARDs - Janus Associated Kinase (JAK) Inhibitors

Abrocitinib Baricitinib Deucravacitinib

Simponi

Subcutaneous injection or intravenous infusion

Tremfya

Subcutaneous injection

Avsola, Inflectra, Ixifi, Remicade, Renflexis, Zymfentra

Subcutaneous injection or intravenous infusion

Taltz

Subcutaneous injection

Omvoh

Subcutaneous injection or intravenous infusion

Tysabri Gazyva Arzerra, Kesimpta
Skyrizi Riabni, Rituxan, Ruxience, Truxima Kevzara Cosentyx
Actemra, Tofidence
Stelara, Wezlana Cibinqo

Intravenous infusion
Intravenous infusion Subcutaneous injection or intravenous infusion Subcutaneous injection or intravenous infusion
Intravenous infusion
Subcutaneous injection
Subcutaneous injection or intravenous infusion Subcutaneous injection or intravenous infusion Subcutaneous injection or intravenous infusion
Oral

Olumiant

Oral

Sotyktu

Oral

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Fedratinib Momelotinib Pacritinib Ritlecitinib Ruxolitinib Tofacitinib

Inrebic

Oral

Ojjaara

Oral

Vonjo

Oral

Litfulo

Oral

Jakafi

Oral

Xeljanz/Xeljanz XR

Oral

Upadacitinib

Rinvoq

Oral

Targeted synthetic

DMARDs Phosphodiesterase-4

Apremilast

Otezla

Oral

(PDE-4) Inhibitors

NOTE: The above table provides a selection of the commonly prescribed DMARDs in the United States.

It is important to note that this table is not exhaustive, and it may not include some recently approved

drugs or those currently under investigation.  Oral tsDMARDs coverage is subject to Plan benefits and are typically billed through a member's pharmacy benefits.

Definitions Biologic drug class by type of therapeutic molecule/agent:
 "Cell surface receptor antagonist proteins" are inactive proteins that compete with cytokines for binding sites on the cytokine's membrane receptor. The percentage of receptors they need to bind to for effective action can vary depending on the specific drug and condition being treated.
 "Monoclonal antibodies"are laboratory-produced antibodies derived from human or nonhuman sources, engineered to target and recognize specific antigens causing disease. Their affinity for antigens is greater than that of soluble receptor antagonists.
 "Soluble receptor antagonists"are molecules that selectively bind to target cytokines present in the blood, thus preventing the cytokines from interacting with cell surface receptors.

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Biologic response modifier therapies (biologics) drug class by mechanism of action and area of target:
 "Anti-integrin antibody" specifically bind to and inhibit the interaction between integrin alpha4-beta-7 and mucosal addressin cell adhesion molecule-1 (MAdCAM-1) in the gut, thus reducing chronic inflammation associated with ulcerative colitis and Crohn's disease. Natalizumab and vedolizumab are FDA-approved anti-integrin drugs.
 "B-cells inhibitors" impede the activation of B-cells, the cells initiating a cascade reaction resulting in inflammation. B-cell inhibitors include rituximab and belimumab.
 "Interleukin (IL) inhibitors" target interleukins, which are key mediators of inflammation in the body. Anakinra, canakinumab, and rilonacept are common IL-1 inhibitors. IL-6 inhibitors include tocilizumab and sarilumab, while IL-17 inhibitors comprise secukinumab, ixekizumab, or brodalumab. Ustekinumab is a common IL-12/23 inhibitor. Newer IL-23 inhibitors like guselkumab and risankizumab specifically target the p19 subunit of IL-23, providing more selective inhibition.
 "T-cells inhibitors" impede the activation of cytokines influencing systemic inflammation. An example of a T-cell co-stimulation blocker is abatacept.
 "Tumor Necrosis Factor (TNF) inhibitors" specifically target tumor necrosis factor-alpha, an inflammatory cytokine implicated in cell death during inflammation. They halt this inflammatory process and slow disease progression. Examples include infliximab, adalimumab, certolizumab, etanercept, golimumab.
"Concomitant" refers to the use of two or more drugs together as part of a treatment regimen.
"Disease-modifying antirheumatic drugs (DMARDs)" are a class of drugs that modulate the immune system and inflammation. They are categorized as:
1. Conventional/traditional DMARDs: e.g., methotrexate, sulfasalazine, hydroxychloroquine, leflunomide. They are typically the first line of therapy.
2. Biologic DMARDs: These include many of the biologics mentioned above, typically used in patients who do not respond to initial therapy for rheumatoid arthritis. However, it's important to note that not all biologics are necessarily categorized as DMARDs, as some are used for conditions other than rheumatic diseases.
3. Targeted synthetic DMARDs (tsDMARDs): e.g., baricitinib, tofacitinib, apremilast. They are generally prescribed for patients who have failed or have contraindications to conventional DMARDs or biologic DMARDs.
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"Kinase inhibitors" are small-molecule drugs not made from recombinant DNA or proteins; thus, they are not considered biologics. They inhibit various kinases, including Janus kinases (JAK), which are critical for cellular signal transduction pathways. These orally administered medications include tofacitinib and baricitinib, which specifically target JAK, but other kinase inhibitors may target different kinases.
Policy Statement on Concomitant (Concurrent) use of Biologics (Biologic Response Modifiers Therapies) and targeted synthetic Disease-Modifying Antirheumatic Drugs (tsDMARDs) The concurrent use of two or more biologic agents or a biologic agent with a targeted synthetic DMARD (tsDMARD) for the same diagnosis during the same time period is typically considered experimental or investigational and is not considered medically necessary, unless supported by FDA guidelines, clinical criteria, or high-quality clinical evidence.
 Concomitant use of multiple biologics may increase the risk of infection without providing additional clinical benefit.
 Clinical trials have not demonstrated added benefit from concomitant use of certain biologics.  Current treatment guidelines from major rheumatology and dermatology societies do not
recommend routine concurrent use of biologics or biologics with tsDMARDs.
Medical Necessity Criteria for Concomitant (Concurrent) use of Biologics (Biologic Response Modifiers Therapies) and targeted synthetic Disease-Modifying Antirheumatic Drugs (tsDMARDs) The Plan does not consider medically necessary the concurrent use of a biologic when the following criteria are met:
1. The use of two or more biologic agents (Anti-integrin antibody, B-cell inhibitors, IL inhibitors, Tcell inhibitors, TNF inhibitors), for purposes of the same diagnosis during the same time period (unless indicated that there is greater efficacy with concurrent use of biologics by FDA prescribing guidelines, compendia, national society guidelines, clinical criteria or high-quality clinical evidence); or
2. The use of a biologic agent with a targeted synthetic DMARD (tsDMARD), for purposes of the same diagnosis during the same time period, (unless indicated that there is greater efficacy with concurrent use of biologics by FDA prescribing guidelines, compendia, national society guidelines, clinical criteria or high-quality clinical evidence) including but not limited to: a. An oral Janus kinase (JAK) inhibitor (e.g., Olumiant (baricitinib), Rinvoq (upadacitinib), Xeljanz (tofacitinib), Xeljanz XR (tofacitinib)); or b. An oral phosphodiesterase-4 (PDE4) inhibitor (e.g., Otezla (apremilast)).
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Rationale: The current body of evidence is not sufficient to confirm the medical benefits of concurrent use of Biologic Response Modifiers Therapies (biologics) and targeted synthetic Disease-Modifying Antirheumatic Drugs (tsDMARDs). Based on the Plan's review of the available clinical evidence, the Plan maintains the following position:
1. There is not enough information to establish definitive medical necessity criteria for coverage.
2. In line with current evidence, the Plan advises against the concurrent use of biologics and tsDMARDs for the same diagnosis during the same time period, as there is insufficient evidence supporting such practice. This stance prioritizes the safety of our members and directs their treatment towards evidence-based, effective regimens.
3. The concurrent use of these therapies will be classified as experimental, investigational, and unproven until robust clinical evidence suggesting otherwise becomes available.
The Plan considers the concomitant use of various classes of biologic agents including Antiintegrin antibody, B-cell inhibitors, IL inhibitors, and T-cell inhibitors, as well as concomitant use of biologic agents with tsDMARDs, such as JAK inhibitors and PDE4 inhibitors, not medically necessary unless specifically indicated in FDA prescribing guidelines, compendia, national society guidelines, clinical criteria or high-quality clinical evidence.
4. National societies such as the American College of Gastroenterology, American College of Rheumatology, American Academy of Dermatology, National Comprehensive Cancer Network, and National Psoriasis Foundation, currently do not include concurrent use of biologics in their general guidance.
5. FDA prescribing labels often discourage simultaneous usage due to increased risk of severe infections and potential drug interactions.
6. Clinical studies of drugs like Abatacept (Orencia), a T-cell co-stimulation blocker, have failed to demonstrate any enhanced efficacy with concurrent treatment. Instead, patients experienced increased rates of infections and serious infections. The use of TNF inhibitors in conjunction with other biologic agents also lacks compelling evidence supporting its safety and efficacy.
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Experimental or Investigational / Not Medically Necessary The Plan considers concomitant use of Biologic Response Modifiers Therapies (biologics) and targeted synthetic Disease-Modifying Antirheumatic Drugs (tsDMARDs) to be not medically necessary primarily due to lack of substantial high-quality clinical evidence, showing a clear and significant benefit to members when these treatments are used concurrently.
Most of the current scientific evidence and clinical guidelines advocate for a stepwise approach in the treatment of autoimmune diseases, beginning with conventional synthetic DMARDs, then moving to biologics or tsDMARDs if necessary. The simultaneous use of two or more biologics or a combination of a biologic with a tsDMARD is generally not supported by these guidelines, primarily due to concerns about increased risk of severe side effects, such as serious infections, without a commensurate increase in therapeutic benefit.
The concurrent use of these treatments can also compound their individual side effects, potentially posing increased risk of harm to the member. As such, until there is clear, robust evidence from welldesigned clinical trials showing that the combined use of these treatments offers substantial benefits that outweigh the potential risks, such use will be considered experimental, investigational, and unproven.
Concomitant Use of Biologics The concomitant use of multiple biologics generally increases the susceptibility to infection and is not routinely recommended. Practice guidelines from national societies such as the American College of Gastroenterology, American College of Rheumatology, American Academy of Dermatology, National Comprehensive Cancer Network, National Psoriasis Foundation do not generally endorse the concurrent use of biologics (B-cell inhibitors, IL inhibitors, T-cell inhibitors, TNF inhibitors) as part of standard treatment protocols. The Plan recognizes that in certain refractory cases, some recent studies have explored combination therapies under close monitoring. Please consult the most recent FDA prescribing labels for specific indications, contraindications, warnings, and precautions.
Concomitant use of Anti-integrin antibody The Plan does not consider medically necessary the use of anti-integrin antibodies (e.g., Tysabri (natalizumab), Entyvio (vedolizumab)) concurrently with another anti-integrin antibody or TNF inhibitors due to the risk of drug interactions and increased infections, as per current prescribing labels.
Concomitant use of B-cells inhibitors Other biologics
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The Plan does not consider medically necessary the concomitant use of B-cell inhibitors with other biologics due to limited evidence. This includes newer B-cell targeting therapies such as obinutuzumab and ofatumumab.
Concomitant Use of IL inhibitors Other biologics The Plan does not consider medically necessary the concurrent use of IL inhibitors (e.g., Kineret (anakinra), Tremfya (guselkumab), Skyrizi (risankizumab)) with TNF blockers (e.g., infliximab), as there is no established added clinical benefit per FDA labels. Concurrent use of IL inhibitors (e.g., ustekinumab) with other biologic agents has not been sufficiently evaluated in clinical studies for most conditions. However, emerging research in inflammatory bowel disease suggests potential benefits in certain refractory cases, which may be considered on a case-bycase basis.
Concomitant use a of Janus kinase (JAK) inhibitor The Plan does not consider medically necessary the concurrent use of JAK inhibitors (including but not limited to Rinvoq (upadacitinib), Olumiant (baricitinib), Xeljanz (tofacitinib), Cibinqo (abrocitinib), Sotyktu (deucravacitinib), Inrebic (fedratinib), Jakafi (ruxolitinib)) with other JAK inhibitors, biologic DMARDs, or potent immunosuppressants such as azathioprine and cyclosporine. These combinations are not recommended in current prescribing labels due to increased risk of immunosuppression without established additional benefit.
Concomitant Use of T-cell co-stimulation blocker TNF Inhibitor, Biologic DMARDs, JAK inhibitors The Plan does not consider medically necessary the use of T-cell co-stimulation blockers when prescribed with a TNF inhibitor, other biologic DMARDs, or JAK inhibitors, as it is not recommended per FDA labels. The ORENCIA STUDY IV clinical trial demonstrated no benefit and increased risk of infections with concurrent use of abatacept (Orencia) and TNF inhibitor therapy.
Concomitant use of Phosphodiesterase-4 (PDE4) inhibitors PDE4 inhibitors (e.g., Otezla (apremilast)) are not recommended for use concurrently with biologics for Behçet's Disease, moderate-to-severe plaque psoriasis, or active psoriatic arthritis. They should be used as an alternative for members who have failed or have contraindications to conventional DMARDs and/or biologics, as per current clinical pharmacology data and drug interaction databases.
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Concomitant Use of TNF inhibitors Other biologics The Plan does not consider medically necessary the use of TNF inhibitors (e.g., infliximab, etanercept, adalimumab) concurrently with other biologic agents such as IL inhibitors or biologic agents in different drug classes, due to insufficient evidence on safety and efficacy as per FDA guidelines. While some recent small-scale studies in inflammatory bowel disease have explored combination therapy with TNF inhibitors and IL inhibitors, these approaches remain experimental and raise safety concerns. Any such combinations should only be considered in highly refractory cases under expert care and close monitoring, which may be considered on a case-by-case basis.
Biosimilars The above guidance applies equally to reference biologics and their approved biosimilars. The use of biosimilars should follow the same principles of monotherapy or limited combination therapy as their reference products.
Applicable Billing Codes (HCPCS/CPT Codes)
Disclaimer The codes for products listed below are provided for informational purposes only. Inclusion or exclusion of a code does not imply or guarantee coverage or reimbursement by the Plan. The actual coverage or non-coverage of services for an individual member will be determined by the terms and conditions of their policy at the time of service, as well as applicable state and federal law.
For confirmation of coverage, please refer to the member's policy documents, such as the Certificate/Evidence of Coverage, Schedule of Benefits, or Plan Formulary. Alternatively, the Plan can be directly contacted for confirmation. The provision of services is governed by the terms, conditions, and limitations of a member's policy.
As outlined in the aforementioned policy, concurrent use of biologics is not typically considered medically necessary. Coverage for a singular biologic is dependent on the
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members' plan benefits and adherence to the Plan's Clinical Guidelines, including but not limited to the Commercial Preferred Physician-Administered Specialty Drugs (CG052).

CPT/HCPCS Codes for biologics

Anti-integrin antibodies

J2323

Injection, natalizumab, 1 mg

Q5134

Injection, natalizumab-sztn (tyruko), biosimilar, 1 mg

J3380

Injection, vedolizumab, intravenous, 1 mg

C9399/J3590

[vedolizumab (SC)] Unclassified drugs or biologicals/Unclassified biologics

B-cell inhibitors

Code J0490 J3590 J9301 J9302 C9399/J3590 J9311

Description Injection, belimumab, 10 mg [belimumab (SC)] Unclassified biologics Injection, obinutuzumab, 10 mg Injection, ofatumumab, 10 mg [ofatumumab (SC)] Unclassified drugs or biologicals/Unclassified biologics Injection, rituximab 10 mg and hyaluronidase

J9312

Injection, rituximab, 10 mg

Q5115

Injection, rituximab-abbs, biosimilar, (truxima), 10 mg

Q5119

Injection, rituximab-pvvr, biosimilar, (ruxience), 10 mg

Q5123

Injection, rituximab-arrx, biosimilar, (riabni), 10 mg

Janus Associated Kinase (JAK) Inhibitors

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J8499

[Abrocitinib] Prescription drug, oral, non chemotherapeutic, nos

J8499

[Baricitinib] Prescription drug, oral, non chemotherapeutic, nos

J8499 C9399/J8499 C9399/J8499 C9399/J8499 J8499 C9399/J8499 J8499 J7999

[Deucravacitinib] Prescription drug, oral, non chemotherapeutic, nos
[Fedratinib] Unclassified drugs or biologicals/Prescription drug, oral, non chemotherapeutic, nos
[Momelotinib] Unclassified drugs or biologicals/Prescription drug, oral, non chemotherapeutic, nos
[Pacritinib] Unclassified drugs or biologicals/Prescription drug, oral, non chemotherapeutic, nos
[Ritlecitinib] Prescription drug, oral, non chemotherapeutic, nos
[Ruxolitinib] Unclassified drugs or biologicals/Prescription drug, oral, non chemotherapeutic, nos
[Tofacitinib, tofacitinib citrate ER] Prescription drug, oral, non chemotherapeutic, nos
[tofacitinib citrate (bulk powder)] Compounded drug, not otherwise classified

J8499

[Upadacitinib] Prescription drug, oral, non chemotherapeutic, nos

Interleukin inhibitors

C9399/J3590

[Anakinra (SC)] Unclassified drugs or biologicals/Unclassified biologics

C9399/J3590

[Brodalumab (SC)] Unclassified drugs or biologicals/Unclassified biologics

C9399/J3590 C9168 J2267

[Ixekizumab (SC)] Unclassified drugs or biologicals/Unclassified biologics Injection, mirikizumab-mrkz, 1 mg Injection, mirikizumab-mrkz, 1 mg

C9399/J3590

Code Note: Code becomes effective 7/1/24 [mirikizumab-mrkz (SC)] Unclassified drugs or biologicals/Unclassified biologics

5

J2327 C9399/J3590 C9399/J3590 C9166 J3247

Injection, risankizumab-rzaa, intravenous, 1 mg [Risankizumab (SC)] Unclassified drugs or biologicals/Unclassified biologics [Sarilumab (SC)] Unclassified drugs or biologicals/Unclassified biologics Injection, secukinumab, intravenous, 1 mg Injection, secukinumab, intravenous, 1 mg

C9399/J3590 J0638 J1628 J2793 J3262 Q5133 C9399/J3590 C9399/J3590 J3357 J3358 Q5137
Q5138

Code Note: Code becomes effective 7/1/24 [Secukinumab (SC)] Unclassified drugs or biologicals/Unclassified biologics Injection, canakinumab, 1 mg Injection, guselkumab, 1 mg Injection, rilonacept, 1 mg Injection, tocilizumab, 1 mg Injection, tocilizumab-bavi (tofidence), biosimilar, 1 mg [tocilizumab (SC)] Unclassified drugs or biologicals/Unclassified biologics [tocilizumab-aazg (Tyenne)] Unclassified drugs or biologicals/Unclassified biologics Ustekinumab, for subcutaneous injection, 1 mg Ustekinumab, for intravenous injection, 1 mg Injection, ustekinumab-auub (wezlana), biosimilar, subcutaneous, 1 mg
Code Note: Code becomes effective 7/1/24 Injection, ustekinumab-auub (wezlana), biosimilar, intravenous, 1 mg

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Code Note: Code becomes effective 7/1/24

Phosphodiesterase-4 (PDE-4) Inhibitors

J8499

[Apremilast] Prescription drug, oral, non chemotherapeutic, nos

T-cell inhibitors

J0129

Injection, abatacept, 10 mg (code may be used for Medicare when drug administered under the direct supervision of a physician, not for use when drug is self-administered)

J0485

Injection, belatacept, 1 mg

TNF inhibitors

J0135 C9399/J3590 C9399/J3590

Injection, adalimumab, 20 mg
[adalimumab-ryvk (Simlandi)] Unclassified drugs or biologicals/Unclassified biologics
[adalimumab-bwwd (Hadlima)] Unclassified drugs or biologicals/Unclassified biologics

C9399/J3590 C9399/J3590 C9399/J3590 C9399/J3590 C9399/J3590 C9399/J3590

[adalimumab-fkjp (Hulio)] Unclassified drugs or biologicals/Unclassified biologics
[adalimumab-atto (Amjevita)] Unclassified drugs or biologicals/Unclassified biologics
[adalimumab-adaz (Hyrimoz)] Unclassified drugs or biologicals/Unclassified biologics
[adalimumab-aqvh (Yusimry)] Unclassified drugs or biologicals/Unclassified biologics
[adalimumab-adbm (Cyltezo)] Unclassified drugs or biologicals/Unclassified biologics
[adalimumab-aaty (Yuflyma)] Unclassified drugs or biologicals/Unclassified biologics

7

Q5131 Q5132 J0717
J1438 J1602 C9399/J3590

Injection, adalimumab-aacf (idacio), biosimilar, 20 mg
Injection, adalimumab-afzb (abrilada), biosimilar, 10 mg
Injection, certolizumab pegol, 1 mg (code may be used for Medicare when drug administered under the direct supervision of a physician, not for use when drug is self-administered)
Injection, etanercept, 25 mg (code may be used for Medicare when drug administered under the direct supervision of a physician, not for use when drug is self-administered)
Injection, golimumab, 1 mg, for intravenous use
[golimumab (SC)] Unclassified drugs or biologicals/Unclassified biologics

J1745

Injection, infliximab, excludes biosimilar, 10 mg

J1748 C9399/J3590

Injection, infliximab-dyyb (zymfentra), 10 mg [infliximab-dyyb (SC)] Unclassified drugs or biologicals/Unclassified biologics

Q5103

Injection, infliximab-dyyb, biosimilar, (Inflectra), 10 mg

Q5104

Injection, infliximab-abda, biosimilar, (Renflexis), 10 mg

Q5109

Injection, infliximab-qbtx, biosimilar, (Ixifi), 10 mg

Q5121

Injection, infliximab-axxq, biosimilar, (AVSOLA), 10 mg

ICD-10 codes considered NOT medically necessary:

Code Z79 Z79.6 Z79.62 Z79.61 Z79.620

Description Long term (current) drug therapy Long term (current) use of immunomodulators and immunosuppressants Long term (current) use of immunosuppressant Long term (current) use of immunomodulator Long term (current) use of immunosuppressive biologic

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Z79.622

Long term (current) use of Janus kinase inhibitor

References
1. Arthritis Foundation. Biologics. Arthritis.org. https://www.arthritis.org/drugguide/biologics/biologics
2. Abrilada (adalimumab-afzb) [prescribing information]. New York, NY: Pfizer Inc; October 2023. 3. Amjevita (adalimumab) [prescribing information]. Thousand Oaks, CA: Amgen Inc; August 2023. 4. Angeles-Han ST, Ringold S, Beukelman T, et al. 2019 American College of
Rheumatology/Arthritis Foundation guideline for the screening, monitoring, and treatment of juvenile idiopathic arthritis-associated uveitis. Arthritis Care Res (Hoboken). 2019;71(6):703-716. 5. Ballow, M., & Fleisher, T.A. (April 2021). Secondary immunodeficiency induced by biologic therapies. UpToDate.com. https://www.uptodate.com/contents/secondary-immunodeficiencyinduced-by-biologic-therapies?search=Bcell%20inhibitors%20concomitant&source=search_result&selectedTitle=2~150&usage_type=def ault&display_rank=2 6. Bathon J, Robles M, Ximenes AC, et al. Sustained disease remission and inhibition of radiographic progression in methotrexate-naive patients with rheumatoid arthritis and poor prognostic factors treated with abatacept: 2-year outcomes. Ann Rheum Dis. 2011;70(11):19491956. 7. Benlysta (belimumab) [prescribing information]. Durham, NC: GlaxoSmithKline LLC; May 2024. 8. Budtarad, N., Prawjaeng, J., Leelahavarong, P., Pilasant, S., Chanjam, C., Narongroeknawin, P., Kitumnuaypong, T., & Katchamart, W. (2023). Efficacy and safety of biologic, biosimilars and targeted synthetic DMARDs in moderate-to-severe rheumatoid arthritis with inadequate response to methotrexate: a systematic review and network meta-analysis. . https://doi.org/10.1101/2023.01.20.23284852. 9. Burmester, G.R. (Nov. 2020). Overview of biologic agents and kinase inhibitors in the rheumatic diseases. UpToDate.com. https://www.uptodate.com/contents/overview-of-biologic-agents-andkinase-inhibitors-in-the-rheumaticdiseases?search=biologics&source=search_result&selectedTitle=1~150&usage_type=default&di splay_rank=1#H3220612907 10. Cibinqo (abrocitinib) [prescribing information]. New York, NY: Pfizer Labs; December 2023. 11. Coates, L.C., Soriano, E.R., Corp, N. et al. Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA): updated treatment recommendations for psoriatic arthritis 2021. Nat Rev Rheumatol 18, 465­479 (2022). https://doi.org/10.1038/s41584-022-00798-0 12. Cohen, S., & Cannella, A. (Dec 2019). Patient education: Disease-modifying antirheumatic drugs (DMARDs) in rheumatoid arthritis (Beyond the Basics). UpToDate.com. https://www.uptodate.com/contents/disease-modifying-antirheumatic-drugs-dmards-inrheumatoid-arthritis-beyond-the-basics#H2 13. Cohen, S., & Cannella, A. (Jan 2020). Treatment of rheumatoid arthritis in adults resistant to initial conventional nonbiologic DMARD therapy. UpToDate.com. https://www.uptodate.com/contents/treatment-of-rheumatoid-arthritis-in-adults-resistant-toinitial-conventional-nonbiologic-dmard-therapy?search=targeted%20synthetic%20diseasemodifying%20antirheumatic%20drug&source=search_result&selectedTitle=1~150&usage_type= default&display_rank=1
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14. Cyltezo (adalimumab) [prescribing information]. Ridgefield, CT: Boehringer Ingelheim Pharmaceuticals Inc; April 2024.
15. Elmets CA, Korman NJ, Prater EF et al. Joint AAD-NPF Guidelines of care for the management and treatment of psoriasis with topical therapy and alternative medicine modalities for psoriasis severity measures. J Am Acad Dermatol. 2021; 84:432-470.
16. Elsevier. (Oct 2019). Apremilast, Otezla, Description/Classification. www.clinicalkey.com. https://www.clinicalkey.com/pharmacology/monograph/3844?sec=mondesc&n=Otezla
17. Feuerstein, J.D., Isaacs, K.L., Schneider, Y., et al. (April 2020). AGA clinical practice guidelines on the management of moderate to severe ulcerative colitis. Gastroenterology,158(5), 1450-1461. doi:10.1053/j.gastro.2020.01.006.
18. Fraenkel L, Bathon JM, England BR, et al. 2021 American College of Rheumatology guideline for the treatment of rheumatoid arthritis. Arthritis Care Res (Hoboken). 2021;73(7):924-939.
19. Fraenkel, L., Bathon, J.M., England, B.R., St.Clair, E.W., Arayssi, T., Carandang, K., Deane, K.D., Genovese, M., Huston, K.K., Kerr, G., Kremer, J., Nakamura, M.C., Russell, L.A., Singh, J.A., Smith, B.J., Sparks, J.A., Venkatachalam, S., Weinblatt, M.E., Al-Gibbawi, M., Baker, J.F., Barbour, K.E., Barton, J.L., Cappelli, L., Chamseddine, F., George, M., Johnson, S.R., Kahale, L., Karam, B.S., Khamis, A.M., Navarro-Millán, I., Mirza, R., Schwab, P., Singh, N., Turgunbaev, M., Turner, A.S., Yaacoub, S. and Akl, E.A. (2021), 2021 American College of Rheumatology Guideline for the Treatment of Rheumatoid Arthritis. Arthritis Care Res, 73: 924-939. https://doi.org/10.1002/acr.24596
20. Gazyva (obinutuzumab) [prescribing information]. South San Francisco, CA: Genentech Inc; July 2022.
21. Hadlima (adalimumab-bwwd) [prescribing information]. Jersey City, NJ: Organon LLC; July 2023. 22. Hirten, R.P., Iacucci, M., Shah, S., et al. (Sept 2018). Combining Biologics in Inflammatory Bowel
Disease and Other Immune Mediated Inflammatory Disorders. Clinical Gastroenterology and Hepatology, 16(9), 1374-1384. Doi: https://doi.org/10.1016/j.cgh.2018.02.024 23. Hulio (adalimumab-fkjp) [prescribing information]. Cambridge, MA: Bicon Biologics Inc; December 2023. 24. Hyrimoz (adalimumab-adaz) [prescribing information]. Princeton, NJ: Sandoz Inc; September 2023. 25. Idacio (adalimumab) [prescribing information]. Lake Zurich, IL: Fresenius Kabi USA LLC; October 2023. 26. Ilaris (canakinumab) [prescribing information]. East Hanover, NJ: Novartis Pharmaceuticals Corp; August 2023. 27. Ko CW, Singh S, Feuerstein JD et al. AGA Clinical Practice Guidelines on the Management of Mild-to-Moderate Ulcerative Colitis. Gastroenterology. 2019; 156:748-764. 28. Manis, J.P. (Dec. 2020). Overview of therapeutic monoclonal antibodies. UpToDate.com. https://www.uptodate.com/contents/overview-of-therapeutic-monoclonalantibodies?search=monoclonal%20antibodies&source=search_result&selectedTitle=1~150&usa ge_type=default&display_rank=1 29. Menter A, Cordoro KM, Davis DMR et al. Joint American Academy of Dermatology-National Psoriasis Foundation guidelines of care for the management and treatment of psoriasis in pediatric patients. J Am Acad Dermatol. 2020; 82:161-201. 30. Menter A, Strober BE, Kaplan DH et al. Joint AAD-NPF guidelines of care for the management and treatment of psoriasis with biologics. J Am Acad Dermatol. 2019; 80:1029-1072.
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31. National Cancer Institute at the National Institutes of Health. Biological response modifier therapy. cancer.gov. https://www.cancer.gov/publications/dictionaries/cancerterms/def/biological-response-modifier-therapy
32. National Comprehensive Cancer Network. (March 2021). Clinical Practice Guidelines in Oncology (NCCN Guidelines), Hodgkin Lymphoma, Version 3.2021. NCCN.org. https://www.nccn.org/professionals/physician_gls/pdf/hodgkins.pdf
33. National Comprehensive Cancer Network. (March 2021). NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines), B-Cell Lymphomas, Version 3.2021. NCCN.org. https://www.nccn.org/professionals/physician_gls/pdf/b-cell.pdf
34. Olumiant [package insert]. Indianapolis, IN: Eli Lilly and Company; 2020. https://uspl.lilly.com/olumiant/olumiant.html#pi
35. Omvoh (mirikizumab) [prescribing information]. Indianapolis, IN: Eli Lilly and Company; April 2024.
36. Ravelli A, Consolaro A, Horneff G, et al. Treating juvenile idiopathic arthritis to target: recommendations of an international task force. Ann Rheum Dis. 2018;77(6):819-828.
37. Rigby, W.F.C, Mease P.J., Olech, E., et al. (May 2013). Safety of Rituximab in Combination with Other Biologic Disease-modifying Antirheumatic Drugs in Rheumatoid Arthritis: An Open-label Study. The Journal of Rheumatology, 40 (5), 599-604. DOI: https://doi.org/10.3899/jrheum.120924
38. Ringold S, Angeles-Han ST, Beukelman T, et al. 2019 American College of Rheumatology/Arthritis Foundation guideline for the treatment of juvenile idiopathic arthritis: therapeutic approaches for non-systemic polyarthritis, sacroiliitis, and enthesitis. Arthritis Care Res (Hoboken). 2019;71(6):717-734.
39. RINVOQ [package insert]. North Chicago, IL: AbbVie Inc. https://www.rxabbvie.com/pdf/rinvoq_pi.pdf
40. Rubin DT, Ananthakrishnan AN, Siegel CA et al. ACG Clinical Guideline: Ulcerative Colitis in Adults. Am J Gastroenterol. 2019; 114:384-413.
41. Sapkota, B., Makandar, S.N., & Acharya, S. (2020). Biologic Response Modifiers (BRMs). StatPearls [Internet], Treasure Island (FL): StatPearls Publishing. https://www.ncbi.nlm.nih.gov/books/NBK542200/
42. Schiff M, Weinblatt ME, Valente R, et al. Head-to-head comparison of subcutaneous abatacept versus adalimumab for rheumatoid arthritis: two-year efficacy and safety findings from AMPLE trial. Ann Rheum Dis. 2014;73(1):86-94.Rubbert-Roth A, Enejosa J, Pangan AL, et al. Trial of upadacitinib or abatacept in rheumatoid arthritis (SELECT-CHOICE). N Engl J Med. 2020;383:1511-1521.
43. Siliq (brodalumab) [prescribing information]. Bridgewater, NJ: Bausch Health US LLC; June 2020. 44. Simlandi (adalimumab) [prescribing information]. Parsippany, NJ: Teva Pharmaceuticals;
February 2024. 45. Singh JA, Guyatt G, Ogdie A, et al. Special article: 2018 American College of
Rheumatology/National Psoriasis Foundation guideline for the treatment of psoriatic arthritis. Arthritis Rheumatol. 2019;71(1):5-32. 46. Singh, J. A., Saag, K. G., Bridges Jr, S. L., Akl, E. A., Bannuru, R. R., Sullivan, M. C., ... & McAlindon, T. (2016). 2015 American College of Rheumatology guideline for the treatment of rheumatoid arthritis. Arthritis & rheumatology, 68(1), 1-26. 47. Singh, J.A., Guyatt, G., Ogdie, A., et al. (Nov. 2018). 2018 American College of Rheumatology/National Psoriasis Foundation Guideline for the treatment of psoriatic arthritis. Arthritis & Rheumatology, 1-28. doi: 10.1002/art.40726
11

48. Skyrizi (risankizumab-rzaa) [prescribing information]. North Chicago, IL: AbbVie Inc; January 2024.
49. Smolen, J. S., Landewé, R., Bijlsma, J., Burmester, G., Chatzidionysiou, K., Dougados, M., ... & Van Der Heijde, D. (2017). EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2016 update. Annals of the rheumatic diseases, 76(6), 960-977.
50. Smolen, J. S., Schöls, M., Braun, J., Dougados, M., FitzGerald, O., Gladman, D. D., ... & Van Der Heijde, D. (2018). Treating axial spondyloarthritis and peripheral spondyloarthritis, especially psoriatic arthritis, to target: 2017 update of recommendations by an international task force. Annals of the rheumatic diseases, 77(1), 3-17.
51. STELARA® (ustekinumab). (2020). STELARA® (ustekinumab) Has Expanded First-Line Biologic* Access for Your Patients1. Concomitant Therapies. Stelarahcp.com. https://www.stelarahcp.com/psoriatic-arthritis/support
52. Togt, C., Bemt, B., Aletaha, D., Alten, R., Chatzidionysiou, K., Galloway, J., Isaac, J., Mulleman, D., Verschueren, P., Vulto, A., Welsing, P., Verhoef, L., & Broeder, A. (2023). Points to consider for cost-effective use of biological and targeted synthetic DMARDs in inflammatory rheumatic diseases: results from an umbrella review and international Delphi study. RMD Open, 9. https://doi.org/10.1136/rmdopen-2022-002898.
53. U.S. Food & Drug Administration (FDA). (April 2020). OTEZLA (apremilast) tablets, for oral use. FDA.gov. https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/205437Orig1s008lbl.pdf
54. U.S. Food & Drug Administration (FDA). (June 2020). ORENCIA (abatacept) for injection, for intravenous use. ORENCIA (abatacept) injection, for subcutaneous use. Packageinserts.bms.com. https://packageinserts.bms.com/pi/pi_orencia.pdf
55. U.S. Food & Drug Administration (FDA). (June 2020). TYSABRI (natalizumab) injection, for intravenous use. www.tysabri.com. https://www.tysabri.com/content/dam/commercial/tysabri/pat/en_us/pdf/tysabri_prescribing_inf ormation.pdf
56. U.S. Food & Drug Administration (FDA). (March 2020). ENTYVIO (vedolizumab) for injection, for intravenous use. Fda.gov. https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/125476s025s030lbl.pdf
57. U.S. Food & Drug Administration (FDA). (May 2020). REMICADE (infliximab) for injection, for intravenous use. Fda.gov. https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/103772s5389s5391s5394lbl.pdf
58. U.S. Food & Drug Administration (FDA). Resources for You (Biologics). Fda.gov. https://www.fda.gov/vaccines-blood-biologics/resources-you-biologics
59. Ward, M. M., Deodhar, A., Gensler, L. S., Dubreuil, M., Yu, D., Khan, M. A., ... & Caplan, L. (2019). 2019 update of the American College of Rheumatology/Spondylitis Association of America/Spondyloarthritis Research and Treatment Network recommendations for the treatment of ankylosing spondylitis and nonradiographic axial spondyloarthritis. Arthritis care & research, 71(10), 1285-1299.
60. Yang, E., Panaccione, N., Whitmire, N., et al. (April 2020). Efficacy and safety of simultaneous treatment with two biologic medications in refractory Crohn's disease. Alimentary Pharmacology and Therapeutics, 51(11), 1031-1038. https://doi.org/10.1111/apt.15719
61. Yuflyma (adalimumab) [prescribing information]. Jersey City, NJ: Celltrion USA Inc; January 2024. 62. Yusimry (adalimumab-aqvh) [prescribing information]. Redwood City, CA: Coherus BioSciences
Inc; September 2023.
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Clinical Guideline Revision / History Information Original Date: 6/24/2021 Reviewed/Revised: 12/01/2021, 06/23/2022, 06/29/2023, 06/27/2024
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References

• Arthritis Foundation | Arthritis Support, Resources, Research & Advocacy
• Comprehensive Cancer Information - NCI
• Evidence-based Clinical Solutions for Healthcare | UpToDate | Wolters Kluwer
• ClinicalKey
• Redirecting
• These highlights do not include all the information needed to use OLUMIANT safely and effectively. See full prescribing information for OLUMIANT.OLUMIANT (baricitinib) tablets, for oral useInitial U.S. Approval: 2018
• Login - Clinical Pharmacology
• Resources for You (Biologics) | FDA
• Biologic Response Modifiers (BRMs) - StatPearls - NCBI Bookshelf