CMS Pub. 100-03, (National Coverage Determinations Manual), Chapter 1, Section 280.14

For any item to be covered by Medicare, it must 1) be eligible for a defined Medicare benefit category, 2) be reasonable and necessary for the diagnosis or treatment of illness or injury or to improve the functioning of a malformed body member, and 3) meet all other applicable Medicare statutory and regulatory requirements.

The purpose of a Local Coverage Determination (LCD) is to provide information regarding “reasonable and necessary” criteria based on Social Security Act § 1862(a)(1)(A) provisions.

In addition to the “reasonable and necessary” criteria contained in this LCD there are other payment rules, which are discussed in the following documents, that must also be met prior to Medicare reimbursement:

• The LCD-related Standard Documentation Requirements Article, located at the bottom of this policy under the Related Local Coverage Documents section.
• The LCD-related Policy Article, located at the bottom of this policy under the Related Local Coverage Documents section.
• Refer to the Supplier Manual for additional information on documentation requirements.
• Refer to the DME MAC web sites for additional bulletin articles and other publications related to this LCD.

For the items addressed in this LCD, the "reasonable and necessary" criteria, based on Social Security Act § 1862(a)(1)(A) provisions, are defined by the following coverage indications, limitations and/or medical necessity.

Payment may be made for supplies that are necessary for the effective use of durable medical equipment. Such supplies include those drugs and biologicals which must be put directly into the equipment in order to achieve the therapeutic benefit of the durable medical equipment or to assure the proper functioning of the equipment. However, the coverage of such drugs or biologicals does not preclude the need for a determination that the drug or biological itself is reasonable and necessary for treatment of the illness or injury or to improve the functioning of a malformed body member.

An external infusion pump is covered for the following indications (I-V):

An infusion pump described by codes E0779, E0780, E0781, and E0791 is covered for indications I – III, V(A) – V(D), V(F), V(G), V(I) and V(J). Coverage of other pumps is addressed under indications IV, V (E), and V (H).

1. Administration of deferoxamine for the treatment of chronic iron overload.
2. Administration of chemotherapy for the treatment of primary hepatocellular carcinoma or colorectal cancer where this disease is unresectable or where the beneficiary refuses surgical excision of the tumor. Anticancer chemotherapy drugs used in these conditions are not required to meet the criteria described by indication V, situation A.
3. Administration of morphine when used in the treatment of intractable pain caused by cancer.
4. Administration of continuous subcutaneous insulin for the treatment of diabetes mellitus (Refer to the ICD-10 code list in the LCD-related Policy Article for applicable diagnoses.) if criterion A or B is met and if criterion C or D is met:
   1. C-peptide testing requirement – must meet criterion 1 or 2 and criterion 3:
      
      1. C-peptide level is less than or equal to 110 percent of the lower limit of normal of the laboratory's measurement method.
      2. For beneficiaries with renal insufficiency and a creatinine clearance (actual or calculated from age, weight, and serum creatinine) less than or equal to 50 ml/minute, a fasting C-peptide level is less than or equal to 200 per cent of the lower limit of normal of the laboratory’s measurement method.
      3. A fasting blood sugar obtained at the same time as the C-peptide level is less than or equal to 225 mg/dl.
   2. Beta cell autoantibody test is positive.
   3. The beneficiary has completed a comprehensive diabetes education program, has been on a program of multiple daily injections of insulin (i.e., at least 3 injections per day) with frequent self-adjustments of insulin dose for at least 6 months prior to initiation of the insulin pump, and has documented frequency of glucose self-testing an average of at least 4 times per day during the 2 months prior to initiation of the insulin pump, and meets one or more of the following criteria (1 - 5) while on the multiple injection regimen:
      1. Glycosylated hemoglobin level (HbA1C) greater than 7 percent
      2. History of recurring hypoglycemia
      3. Wide fluctuations in blood glucose before mealtime
      4. Dawn phenomenon with fasting blood sugars frequently exceeding 200 mg/dL
      5. History of severe glycemic excursions
   4. The beneficiary has been on an external insulin infusion pump prior to enrollment in Medicare and has documented frequency of glucose self-testing an average of at least 4 times per day during the month prior to Medicare enrollment.
   
   If criterion A or B is not met, the pump and related accessories, supplies, and insulin will be denied as not reasonable and necessary. If criterion C or D is not met, the pump and related accessories, supplies, and insulin will be denied as not reasonable and necessary.
   
   Continued coverage of an external insulin pump and supplies requires that the beneficiary be seen and evaluated by the treating practitioner at least every 3 months. In addition, the external insulin infusion pump must be ordered and follow-up care rendered by a practitioner who manages multiple beneficiaries on continuous subcutaneous insulin infusion therapy and who works closely with a team including nurses, diabetic educators, and dieticians who are knowledgeable in the use of continuous subcutaneous insulin infusion therapy.
   
   Subcutaneous insulin is administered using ambulatory infusion pump E0784. Claims for usage of infusion pumps other than E0784 will be denied as not reasonable and necessary.
   
   The HCPCS code combination of E0784 plus K0554 is used to describe external ambulatory insulin infusion pumps that incorporate dose rate adjustment using therapeutic continuous glucose sensing. Coverage for this HCPCS code combination is only met if the beneficiary meets all the coverage criteria for insulin pumps outlined in this policy and all criteria for a therapeutic Continuous Glucose Monitor (CGM) as outlined in the Glucose Monitors policy (LCD L33822).
   
   Refer to the GENERAL section below, and to the CODING GUIDELINES section in the LCD-related Policy Article for additional information regarding supplies used in conjunction with insulin infusion pumps (E0784).
   
   Claims with dates of service on or after January 01, 2017 for supply HCPCS codes A4221, A4222 and K0552, when used with an external infusion pump HCPCS code E0784 will be denied as incorrect coding.
   
   
5. Administration of other drugs if either of the following sets of criteria (1) or (2) are met:
   • Criteria set 1:
     • Parenteral administration of the drug in the home is reasonable and necessary
     • An infusion pump is necessary to safely administer the drug
     • The drug is administered by a prolonged infusion of at least 8 hours because of proven improved clinical efficacy
     • The therapeutic regimen is proven or generally accepted to have significant advantages over intermittent bolus administration regimens or infusions lasting less than 8 hours
   • Criteria set 2: 
     • Parenteral administration of the drug in the home is reasonable and necessary
     • An infusion pump is necessary to safely administer the drug
     • The drug is administered by intermittent infusion (each episode of infusion lasting less than 8 hours) which does not require the beneficiary to return to the practitioner's office prior to the beginning of each infusion
     • Systemic toxicity or adverse effects of the drug are unavoidable without infusing it at a strictly controlled rate as indicated in the Physicians Desk Reference, or the U.S. Pharmacopeia Drug Information

Coverage for the administration of other drugs, based on criteria set (1) or (2), using an external infusion pump is limited to the following situations (A) - (J):

1. Administration of the anticancer chemotherapy drugs cladribine, fluorouracil, cytarabine, bleomycin, floxuridine, doxorubicin (non-liposomal), vincristine (non-liposomal) or vinblastine by continuous infusion over at least 8 hours when the regimen is proven or generally accepted to have significant advantages over intermittent administration regimens 

2. Administration of narcotic analgesics (except meperidine) in place of morphine to a beneficiary with intractable pain caused by cancer that has not responded to an adequate oral/transdermal therapeutic regimen and/or cannot tolerate oral/transdermal narcotic analgesics

3. Administration of the following antifungal or antiviral drugs: acyclovir, foscarnet, amphotericin B, and ganciclovir

4. Administration of parenteral inotropic therapy using the drugs dobutamine (J1250), milrinone (J2260) or dopamine (J1265) for beneficiaries with American College of Cardiology Foundation/American Heart Association (ACCF/AHA) Stage D heart failure (HF) or New York Heart Association (NYHA) Class IV HF, if a beneficiary meets all of the following criteria: 
   1. Remains symptomatic despite optimal guideline directed medical therapy (GDMT) as defined below; and,
   2. As “Bridge” therapy for patients eligible for and awaiting mechanical circulatory support (MCS)/cardiac transplantation, or as palliative care for patients not eligible for either MCS/cardiac transplantation; and,
   3. Prescribed following an evaluation by a cardiologist with training in the management of advanced heart failure; and,
   4. There has been a documented improvement in beneficiary symptoms of heart failure while on the selected inotropic drug at the time of discharge from an inpatient or skilled nursing care facility; and,
   5. An evaluation every three months by the prescribing provider or a heart failure team with oversight by a cardiologist with training in the management of advanced heart failure, which documents the beneficiary’s cardiac symptoms and the continuing response and need for therapy. The heart failure team or practitioner may have no financial relationship with the supplier.

Guideline-directed medical therapy (GDMT) is compliance with optimal medical therapy as defined by ACCF/AHA guideline–recommended therapies (primarily Class I recommendations). These include the use of diuretics, ACE inhibitors or ARB antagonists, beta-blockers, aldosterone antagonists, hydralazine & isosorbide dinitrate, and statins, as appropriate.

For an external infusion pump and related inotropic drugs covered prior to 12/01/2015, if the Medicare coverage criteria in effect on the initial date of service were met, the pump and drug(s) will continue to be covered for claims with dates of service on or after 12/01/2015 as long as the beneficiary continues to meet medical need.

5. Administration of epoprostenol (J1325) or treprostinil (J3285) for beneficiaries with pulmonary hypertension if they meet the following disease criteria:
   1. The pulmonary hypertension is not secondary to pulmonary venous hypertension (e.g., left sided atrial or ventricular disease, left sided valvular heart disease, etc.) or disorders of the respiratory system (e.g., chronic obstructive pulmonary disease, interstitial lung disease, obstructive sleep apnea or other sleep disordered breathing, alveolar hypoventilation disorders, etc.); and
   2. The beneficiary has primary pulmonary hypertension or pulmonary hypertension, which is secondary to one of the following conditions: connective tissue disease, thromboembolic disease of the pulmonary arteries, human immunodeficiency virus (HIV) infection, cirrhosis, diet drugs, congenital left to right shunts, etc. If these conditions are present, the following criteria must be met:
      1. The pulmonary hypertension has progressed despite maximal medical and/or surgical treatment of the identified condition; and,
      2. The mean pulmonary artery pressure is greater than 25 mm Hg at rest or greater than 30 mm Hg with exertion; and,
      3. The beneficiary has significant symptoms from the pulmonary hypertension (i.e., severe dyspnea on exertion, and either fatigability, angina, or syncope); and,
      4. Treatment with oral calcium channel blocking agents has been tried and failed, or has been considered and ruled out.
      5. Epoprostenol/treprostinil is administered using ambulatory infusion pump K0455. Claims for usage of infusion pumps other than K0455 will be denied as not reasonable and necessary.
6. Gallium nitrate (J1457) is covered for the treatment of symptomatic cancer-related hypercalcemia (Refer to the ICD-10 code list in the LCD-related Policy Article for applicable diagnoses.). In general, beneficiaries with serum calcium (corrected for albumin) less than 12 mg/dl would not be expected to be symptomatic.
   
   The recommended usage for gallium nitrate is daily for five consecutive days. Use for more than 5 days will be denied as not reasonable and necessary.
   
   More than one course of treatment for the same episode of hypercalcemia will be denied as not reasonable and necessary.
   
   
7. Ziconotide (J2278) is covered for the management of severe chronic pain in beneficiaries for whom intrathecal (IT or epidural) therapy is warranted, and who are intolerant of or refractory to other treatment, such as systemic analgesics, adjunctive therapies, or IT morphine.
   
   
8. Subcutaneous immune globulin (J1555, J1558, J1559, J1561, J1562, J1569, J1575, and J7799 (Cutaquig^®)) is covered only if criteria 1 and 2 are met:

1. The subcutaneous immune globulin preparation is a pooled plasma derivative which is approved for the treatment of primary immune deficiency disease; and,
2. The beneficiary has a diagnosis of primary immune deficiency disease. (Refer to the ICD-10 code list in the LCD-related Policy Article for applicable diagnoses.)

Coverage of subcutaneous immune globulin applies only to those products that are specifically labeled as subcutaneous administration products. Intravenous immune globulin products are not covered under this LCD.

For the administration of subcutaneous immune globulins with the following HCPCS codes - J1555, J1559, J1561, J1562, and J1569, only an E0779 infusion pump is covered. If a different pump is used, it will be denied as not reasonable and necessary.

For the administration of subcutaneous immune globulin with HCPCS code J1575, only an E0781 infusion pump is covered. If a different pump is used, it will be denied as not reasonable and necessary.

For the administration of subcutaneous immune globulin with HCPCS code J1558 and J7799 (Cutaquig) either an E0779 or an E0781 infusion pump is covered. If a different pump is used, it will be denied as not reasonable and necessary.

9. Levodopa-Carbidopa enteral suspension (J7340) is only covered for treatment of motor fluctuations in beneficiaries with Parkinson’s disease (PD), who meet all of the following criteria (Refer to the ICD-10 code list in the LCD-related Policy Article for applicable diagnoses.):
   1. The beneficiary has been evaluated by a neurologist, who prescribes and manages treatment with the drug; and,
   2. Idiopathic PD based on the presence of bradykinesia and at least one other cardinal PD features (tremor, rigidity, postural instability); and,
   3. L-dopa responsive with clearly defined “On” periods; and,
   4. Persistent motor complications with disabling “Off” periods for a minimum of 3 hours/day, despite medical therapy with levodopa-carbidopa, and at least one other class of anti-PD therapy i.e. COMT inhibitor or MAO-B inhibitor.

Levodopa-Carbidopa enteral suspension is not reasonable and necessary for patients with any of the following:

9. 1. Atypical Parkinson’s syndrome (“Parkinson’s Plus” syndrome) or secondary Parkinson’s; or
   2. Non-levodopa responsive PD; or,
   3. Contraindication to percutaneous endoscopic gastro-jejunal (PEG-J) tube placement or long-term use of a PEG-J.

Establishment of the transabdominal port with a PEG-J is performed under endoscopic guidance by a gastroenterologist or other healthcare provider experienced in this procedure. The PEG-J is considered a supply provided incident to a physician's service, and claims for this item are processed by the A/B MAC contractor. Claims to the DME MAC for the PEG-J will be rejected as wrong jurisdiction.

10. Blinatumomab (J9039) is only covered for:
    1. Up to nine (9) cycles for adult and pediatric beneficiaries with relapsed or refractory (R/R) B-cell precursor acute lymphoblastic leukemia (ALL); or
    2. Up to four (4) cycles for adult and pediatric beneficiaries with B-cell precursor ALL in first or second remission with minimal residual disease (MRD) greater than or equal to 0.1%.

(Refer to the ICD-10 code list in the LCD-related Policy Article for applicable diagnoses.)

Maximum utilization is 875 units of service (UOS), which is equivalent to 25 vials per month. Claims for more than 875 UOS (25 vials) will be denied as not reasonable and necessary. Refer to the CODING GUIDELINES section of the related Policy Article for information regarding units of service.

 
GENERAL

External infusion pumps and related drugs and supplies will be denied as not reasonable and necessary when the criteria described by indication (I), (II), (III), (IV) or (V) are not met.

When an infusion pump is covered, the drug necessitating the use of the pump and necessary supplies are also covered. When a pump has been purchased by the Medicare program, other insurer, the beneficiary, or the rental cap has been reached, the drug necessitating the use of the pump and supplies are covered as long as the coverage criteria for the pump are met.

An external infusion pump and related drugs and supplies will be denied as not reasonable and necessary in the home setting for the treatment of thromboembolic disease and/or pulmonary embolism by heparin infusion.

An infusion controller device (E1399) is not reasonable and necessary.

An IV pole (E0776) is covered only when a stationary infusion pump (E0791) is covered. It is considered not reasonable and necessary if it is billed with an ambulatory infusion pump (E0779, E0780, E0781, E0784, or K0455).

Supplies for the maintenance of a parenteral drug infusion catheter (A4221) or supplies for the maintenance for an insulin infusion pump (A4224) are covered during the period of covered use of an infusion pump. They are also covered for the weeks in between covered infusion pump use, not to exceed 4 weeks per episode.

Supplies used with an external infusion pump, A4222 and K0552 or supplies used with an insulin infusion pump (A4225) are covered during the period of covered use of an infusion pump. Allowance is based on the number of cassettes or bags (A4222) prepared or syringes (A4225, K0552) used. For intermittent infusions, no more than one cassette or bag is covered for each dose of drug. For continuous infusion, the concentration of the drug and the size of the cassette, bag, or syringe should be maximized to result in the fewest cassettes, bags, or syringes in keeping with good pharmacologic and medical practice.

Claims with dates of service on or after January 01, 2017 for supply HCPCS codes A4224 and A4225 used with an external infusion pump other than HCPCS code E0784 will be denied as incorrect coding.

Drugs and supplies that are dispensed but not used for completely unforeseen circumstances (e.g., emergency admission to hospital, drug toxicity, etc.) are covered. Suppliers are expected to anticipate changing needs for drugs (e.g., planned hospital admissions, drug level testing with possible dosage change, etc.) in their drug and supply preparation and delivery schedule.

Charges for drugs administered by a DME infusion pump may only be billed by the entity that actually dispenses the drug to the Medicare beneficiary and that entity must be permitted under all applicable federal, state, and local laws and regulations to dispense drugs. Only entities licensed in the state where they are physically located may bill for infusion drugs. Drugs and related supplies and equipment billed by a supplier who does not meet these criteria will be denied as not reasonable and necessary.

Compounded drugs NOC (J7999) billed with an external infusion pump will be denied as not reasonable and necessary. Refer to the CODING GUIDELINES section of the related Policy Article for information about J7999 coding requirements.

Claims for compounded drugs that do not use code Q9977 or J7999 will be denied as incorrect coding.

A Standard Written Order (SWO) must be communicated to the supplier before a claim is submitted. If the supplier bills for an item addressed in this policy without first receiving a completed SWO, the claim shall be denied as not reasonable and necessary.

For Durable Medical Equipment, Prosthetics, Orthotics and Supplies (DMEPOS) base items that require a Written Order Prior to Delivery (WOPD), the supplier must have received a signed SWO before the DMEPOS item is delivered to a beneficiary. If a supplier delivers a DMEPOS item without first receiving a WOPD, the claim shall be denied as not reasonable and necessary. Refer to the LCD-related Policy Article, located at the bottom of this policy under the Related Local Coverage Documents section.

For DMEPOS base items that require a WOPD, and also require separately billed associated options, accessories, and/or supplies, the supplier must have received a WOPD which lists the base item and which may list all the associated options, accessories, and/or supplies that are separately billed prior to the delivery of the items. In this scenario, if the supplier separately bills for associated options, accessories, and/or supplies without first receiving a completed and signed WOPD of the base item prior to delivery, the claim(s) shall be denied as not reasonable and necessary.

An item/service is correctly coded when it meets all the coding guidelines listed in CMS HCPCS guidelines, LCDs, LCD-related Policy Articles, or DME MAC articles. Claims that do not meet coding guidelines shall be denied as not reasonable and necessary/incorrectly coded.

Proof of delivery (POD) is a Supplier Standard and DMEPOS suppliers are required to maintain POD documentation in their files. Proof of delivery documentation must be made available to the Medicare contractor upon request. All services that do not have appropriate proof of delivery from the supplier shall be denied as not reasonable and necessary.

REFILL REQUIREMENTS

For DMEPOS items and supplies provided on a recurring basis, billing must be based on prospective, not retrospective use. For DMEPOS products that are supplied as refills to the original order, suppliers must contact the beneficiary prior to dispensing the refill and not automatically ship on a pre-determined basis, even if authorized by the beneficiary. This shall be done to ensure that the refilled item remains reasonable and necessary, existing supplies are approaching exhaustion, and to confirm any changes or modifications to the order. Contact with the beneficiary or designee regarding refills must take place no sooner than 14 calendar days prior to the delivery/shipping date. For delivery of refills, the supplier must deliver the DMEPOS product no sooner than 10 calendar days prior to the end of usage for the current product. This is regardless of which delivery method is utilized.

For all DMEPOS items that are provided on a recurring basis, suppliers are required to have contact with the beneficiary or caregiver/designee prior to dispensing a new supply of items. Suppliers must not deliver refills without a refill request from a beneficiary. Items delivered without a valid, documented refill request will be denied as not reasonable and necessary.

Suppliers must not dispense a quantity of supplies exceeding a beneficiary's expected utilization. Suppliers must stay attuned to changed or atypical utilization patterns on the part of their clients. Suppliers must verify with the treating practitioners that any changed or atypical utilization is warranted.

Regardless of utilization, a supplier must not dispense more than a three (3) - month quantity at a time.

DRUG WASTAGE

Claims for drugs billed to Medicare must use drug dosage formulations and/or unit dose sizes that minimize wastage. Medicare provides payment for the amount of a single use vial or other single use package of drug or biological discarded, in addition to the dose administered.

Effective for claims with dates of service on or after January 1, 2017, Medicare requires the use of the JW modifier when billing for drug wastage.

Because of the HCPCS code descriptors and the associated UOS for DMEPOS items, the DME MACs expect rare use of the JW modifier on claims.

The amount of drug discarded must be billed on a separate claim line using the JW modifier. Review the POLICY SPECIFIC DOCUMENTATION REQUIREMENTS section in the LCD-related Policy Article for additional instructions regarding the use of the JW modifier.

Effective for claims with dates of service on or after January 1, 2017, if the coverage criteria for the infusion drugs are not met, claims billed for drug wastage with the JW modifier will be denied as not reasonable and necessary.

Effective for claims with dates of service on or after January 1, 2017, claims lines billed for drug wastage without a JW modifier will be denied as not reasonable and necessary.

Background

Cutaquig (Octapharma Pharmazeutika Produktionsges, Vienna, Austria) is a ready-to-use, highly purified and concentrated (16.5%) polyvalent immunoglobulin G (IgG) solution for subcutaneous antibody replacement therapy in patients with primary humoral immunodeficiency disorders. Unique properties that set Cutaquig apart from other SCIG products include a lower viscosity compared to 20% SCIG products, and its sucrose-free, maltose-stabilization. The maltose-stabilization may allow Cutaquig to be an alternative for patients who do not respond well to or have a contraindication to sucrose-stabilized SCIG products; such as, patients with diabetes or who are at risk of renal insufficiency. Cutaquig was approved by the Food & Drug Administration (FDA) on December 12, 2018 for the treatment of primary humoral immunodeficiency in adults.

For full prescribing information, see: https://nctr-crs.fda.gov/fdalabel/services/spl/set-ids/f3de095f-791a-85dc-7a14-ec7790cb13aa/spl-doc#section-3.3

Literature Analysis

In a phase 3, prospective, open-label, non-controlled, single-arm multicenter study¹, Kobayashi et al. investigated the efficacy, safety, tolerability, and pharmacokinetics of Cutaquig human immunoglobulin solution for subcutaneous (SC) administration. The primary efficacy outcome of the study was the prevention of serious bacterial infections (SBI) per person-year on treatment. Secondary outcomes included the tolerability and safety of Cutaquig, and Quality of Life (QoL) measures of patients using Cutaquig. A total of 61 participants with a median age of 34.0 (2.0–73.0) were enrolled in the study and were administered Cutaquig at bioequivelant doses (dose conversion factor of 1.5) to their previously stable IVIG dose. No SBIs occurred in any patients during the study period. There were 14 mild or moderate systemic adverse events (AEs) related to Cutaquig; however, none were classified as serious. The most common site reactions were erythema, swelling, and pruritus, and were mild (89.4%) or moderate (10.3%) in intensity. Health-related quality of life (HRQL) was assessed using the Child Health Questionnaire-Parent (CHQ-PF50) in patients <14 years and Short Form-36 (SF-36) in patients ≥14 years. There was no change in HRQL over time observed in patients <14 years of age; however, there was an increase in mean summary scores (physical health and mental health) noted in patients ≥14 years. The authors concluded that Cutaquig offered protection from infection, with no SBIs and a low rate of other infections with favorable efficacy and safety profiles.

In an 8 month (8-week wash-in/wash-out period plus 6-month efficacy period) phase 3, prospective, open-label, noncontrolled, single-arm, multicenter study², Latysheva et al. evaluated the safety of Octanorm (Cutaquig) administered SC once weekly in adult patients with PIDD previously treated with IVIg. The primary end point of this study was the rate of SBIs. Additional efficacy end points included the annual rate of all infections, use of antibiotics, hospitalizations due to infection, QoL assessment using the 36-item Short Form Health Survey (SF-36), and IgG trough levels. A total of 25 patients (mean age 35.2 years) who had completed ≥4 infusions of any IVIG and had ≥2 IgG trough levels of ≥5.0 g/l during these infusions were recruited, 24 patients completed the study. All patients received Octanorm (Cutaquig) once weekly (±2 days with a minimum of 4 days between doses) by SC infusion via an infusion pump. No SBIs or hospitalizations due to infection were reported through the study period. IgG trough levels were above 5 g/l in all but one patient, in whom IgG trough level dropped below 5 g/l on one occasion during the efficacy period. The rate of all infections was 2.37 (95% CI: 1.24–4.54) per person-year during the efficacy period and 2.30 (95% CI: 1.25–4.20) per person-year in the entire treatment period, with all infections being mild or moderate in severity. Ten patients required antibiotics over 19 treatment episodes. QoL assessed using the SF-36 showed improvement in seven out of the eight multi-item scales with an improvement in mean physical and mental health summary scores. Three treatment-related systemic AEs (musculoskeletal discomfort, dizziness and headache) were reported. All were mild in severity, resolved within 1 day and did not lead to withdrawal of treatment or dosage adjustment. Most infusions (85.0%) were not associated with any infusion site reaction, with the remainder associated with mild or moderate infusion site reactions described as erythema, pruritus and contact dermatitis. The authors concluded that the present study suggested Octanorm (Cutaquig) is effective and safe in adult patients with PIDD; however, also noted several limitation of study, including small sample size with no formal sample size calculations, a lack of data on prophylactic antibiotic use prior to study enrollment, and a lack of a control group.

Evidence Based Guidelines

Canadian Blood Services and the National Advisory Committee of Blood and Blood Products³

Summary of recommendations (in relevant part):

SCIG was considered equally efficacious to IVIG in decreasing the frequency and duration of infection. […]

8. With respect to clinical efficacy and adverse events, there is insufficient evidence to recommend one manufacturer of IG over another for currently available products.

Level of evidence: I – II-2

Grade of recommendation: I

9. With respect to clinical efficacy for reducing infections, IVIG and SCIG preparations should be considered equivalent.

Level of evidence: I and II

Grade of recommendation: B

10. When deciding on route of administration, patient preference should be taken into account.

Level of evidence: III

Grade of recommendation: A

12. Start IVIG at a dose of 400 to 600mg/kg per 4 weeks or SCIG at a dose of 100 to 150 mg/kg per week in most patients.

Level of evidence: III

Grade of recommendation: B

Professional Society Recommendations

Workgroup Report of the American Academy of Allergy, Asthma, & Immunology⁴

Summary of recommendations (in relevant part):

IG is indicated as replacement therapy for patients with PI characterized by absent or deficient antibody production; PI is an FDA-approved indication of immunoglobulin, for which all currently available products are licensed. Route of immunoglobulin administration must be based on patient characteristics; throughout life, certain patients may be more appropriate for IV or SC therapy depending on many factors, and patients should have access to either route as needed.

Australian Society of Clinical Immunology and Allergy⁵

Summary of recommendations (in relevant part):

Both intravenous immunoglobulin (IVIg) and subcutaneous immunoglobulin (SCIg) replacement therapy comprise standard of care treatment and should be available for patients in Australia and New Zealand with antibody deficiency due to a primary immune deficiency (PID) disease or secondary immune deficiency. SCIg infusions for immunoglobulin replacement therapy (IRT) are efficacious, well tolerated, have a favourable safety profile and should be available to all patients where clinically appropriate, with relevant education, training and follow up care.

Level of evidence

Quality: Moderate

Strength: Moderate

Weight: Moderate

Conclusion

Cutaquig is a SCIG preparation approved for the treatment of PIDD. Based on the review of published clinical literature, evidence based clinical guidelines, and professional society recommendations there is sufficient evidence that SCIGs, such as Cutaquig, are safe and efficacious, and improve the health outcomes of beneficiaries with a diagnosis of PIDD. Therefore, the External Infusion Pumps LCD (L33794) will be extended to include coverage of Cutaquig as reasonable and necessary for the treatment of beneficiaries with a diagnosis of PIDD.