MEDICAL POLICY 5.01.19

Injectable Clostridial Collagenase for Fibroproliferative

Disorders BCBSA Ref. Policy: 5.01.19

Effective Date: Feb. 1, 2018

Last Revised: Jan. 30, 2018

Replaces: 5.01.524

RELATED MEDICAL POLICIES:

None

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POLICY CRITERIA | CODING | RELATED INFORMATION

EVIDENCE REVIEW | REFERENCES | HISTORY

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Introduction

Dupuytrens contracture is a hand condition where knots of tissue form beneath the skin of the

palm. Over time these knots create a cord, which pulls on one or more fingers. The cord is

inflexible, causing the fingers to curl into a bent position. The ring finger and pinky fingers are

usually affected, with the middle finger affected less often. Its rare that the index finger and

thumb are affected. The condition advances slows and usually starts with a thickening of skin on

the palm. A knot then forms, followed by another and another. Men older than 50 and of

northern European descent have the highest incidence of Dupuytrens contracture. There are a

few treatment options, one of which calls for injecting a specific enzyme (clostridial collagenase)

into the cord. The enzyme makes the cord softer, allowing it to stretch and break as a doctor

straightens the fingers. The enzyme also has been used to try to treat other conditions. This

policy describes the conditions for which injections of this enzyme may be considered medically

necessary.

Note: The Introduction section is for your general knowledge and is not to be taken as policy coverage criteria. The

rest of the policy uses specific words and concepts familiar to medical professionals. It is intended for

providers. A provider can be a person, such as a doctor, nurse, psychologist, or dentist. A provider also can

be a place where medical care is given, like a hospital, clinic, or lab. This policy informs them about when a

service may be covered.

Page | 2 of 13

Policy Coverage Criteria

Indication Medical Necessity Dupuytren contracture Injectable clostridial collagenase may be considered medically

necessary for the treatment of Dupuytren contracture in adult

patients with a palpable cord, for up to 3 injections at intervals

of at least 30 days.

Physicians should treat no more than 2 joints in the same hand

for Dupuytren contracture per treatment visit, consistent with

U.S. Food and Drug Administration (FDA) labeling.

Note: Product name: Xiaflex (collagenase clostridium histolyticum)

Indication Investigational Peyronie disease

Adhesive capsulitis

Other indications

Injectable clostridial collagenase is considered investigational

for all other indications including, but not limited to, Peyronie

disease and adhesive capsulitis.

Note: Product name: Xiaflex (collagenase clostridium histolyticum)

Coding

Code Description

CPT 20527 Injection, enzyme (eg, collagenase), palmar fascial cord (ie, Dupuytrens contracture)

26341 Manipulation, palmar fascial cord (ie, Dupuytrens cord), post enzyme injection (eg,

collagenase), single cord

54200 Injection procedure for Peyronie disease

HCPCS

J0775 Injection, collagenase clostridium histolyticum, 0.01 mg

Note: CPT codes, descriptions and materials are copyrighted by the American Medical Association (AMA). HCPCS

codes, descriptions and materials are copyrighted by Centers for Medicare Services (CMS).

Page | 3 of 13

Related Information

Benefit Application

Some plans may require prior authorization before injection of collagenase clostridium

histolyticum. For questions about benefit information, providers should contact customer service

using the telephone number on the back of the members identification card.

Evidence Review

Description

Clostridial collagenase is a bacterial collagenase, derived from Clostridium histolyticum, which

has been evaluated for the treatment of fibroproliferative disorders such as Dupuytren

contracture, Peyronie disease, and adhesive capsulitis.

Background

Fibroproliferative Disorders

Fibrotic tissue disorders, characterized by excessive collagen deposits, can affect the

musculoskeletal system, causing pain and limiting movement and reducing joint range of

motion. Examples of fibroproliferative disorders include Dupuytren disease, Peyronie disease,

and adhesive capsulitis. The mechanisms that contribute to the pathology are poorly

understood.

Dupuytren Disease

In Dupuytren disease, collagen deposits in nodules and cords in the palm and fingers and results

in pitting of the overlying cutis and flexion contractures. The mechanisms that contribute to the

pathology are poorly understood. The prevalence of Dupuytren disease is estimated at 3% to

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6% in the general population and increases with advancing age. The disease is more common in

people with diabetes or thyroid disease and among men.1 The standard of care for Dupuytren

disease is surgery, most commonly open fasciectomy. Other surgical procedures are

percutaneous fasciotomy and needle fasciotomy. Surgery is recommended in patients with

functional impairment and metacarpophalangeal joint contractures of 30 or more. There is no

effective pharmacotherapy.

Peyronie Disease

Peyronie disease is the development of abnormal scar tissue, or plaques, in the tunica albuginea

layer of the penis causing distortion, curvature, and pain (usually during erection). It occurs in

3% to 9% of men, most commonly between the ages of 45 and 60 years. In some cases, plaque

does not cause severe pain or curvature, and the condition resolves on its own. In severe cases,

erectile dysfunction can occur. The goal of treatment is to reduce pain and maintain sexual

function. Treatments in early stages (before calcification) include vitamin E or para-

aminobenzoate tablets (eg, Potaba), although studies of oral therapies have demonstrated

inconsistent benefit. Intralesional injection therapy consisting of injection of interferon--2b or

calcium channel-blockers (eg, verapamil) is the current standard of therapy.2 Surgical procedures

involve the excision of hardened tissue and skin graft, the removal or pinching (plication) of

tissue opposite the plaque to reduce curvature (the Nesbit procedure), penile implant, or a

combination of these.

Adhesive Capsulitis

Adhesive capsulitis or frozen shoulder is treated with physical therapy and mobilization in

combination with analgesics or nonsteroidal anti-inflammatory drugs. Corticosteroid injection is

used with caution. The prevalence of adhesive capsulitis is estimated at 2% to 3% in the general

population and increases with advancing age; additionally, adhesive capsulitis is more common

in people with diabetes or thyroid disease and among women.1

Treatment

Injection with clostridial collagenase is intended to provide a nonoperative treatment option for

fibroproliferative disorders. Clostridial collagenase histolyticum is an enzyme produced by the

bacterium Clostridium histolyticum, which has the physiologic effect of breaking down collagen.

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It has been developed and marketed pharmacologically as a treatment for disorders associated

with collagen overdevelopment.

Summary of Evidence

For individuals who have Dupuytren contracture who receive local clostridial collagenase

injection(s), the evidence includes several placebo-controlled, randomized trials, nonrandomized

comparative studies, and single-arm studies along with systematic reviews of these studies.

Relevant outcomes are symptoms, change in disease status, functional outcomes, and quality of

life. The evidence from clinical trials has suggested that injectable clostridial collagenase

provides short-term release of contracture. A comparison of overall outcomes compared with

surgical intervention may be useful; however, randomized studies with direct comparisons are

not available. Some nonrandomized studies comparing clostridial collagenase with surgery

reported similar outcomes with faster return-to-work and return-to-usual activities rates with

clostridial collagenase, but 1 study reported poorer contraction improvement though lower

adverse event rates. Evidence on long-term recurrence rates is somewhat limited, but 3- and 5-

year follow-ups from 1 large registry reported high recurrence rates (47% at 5 years). Although

clostridial collagenase offers the potential benefit of less-invasive treatment for Dupuytren

contracture, gaps in the evidence base related to treatment durability exist. The evidence is

insufficient to determine the effects of the technology on health outcomes.

For individuals who have Peyronie disease who receive local clostridial collagenase injection(s),

the evidence includes two randomized trials and several noncomparative studies. Relevant

outcomes are symptoms, change in disease status, functional outcomes, and quality of life. The

available double-blind, placebo-controlled randomized trials have demonstrated short-term

improvement in penile curvature and self-reported distress from symptoms related to Peyronie

disease. However, evidence demonstrating health outcome improvements is lacking. In addition,

studies comparing clostridial collagenase with other therapies for Peyronie disease are lacking.

The evidence is insufficient to determine the effects of the technology on health outcomes.

For individuals who have adhesive capsulitis who receive local clostridial collagenase injection(s),

the evidence is very limited. Relevant outcomes are symptoms, change in disease status,

functional outcomes, and quality of life. No published literature that addressed the treatment of

adhesive capsulitis with clostridial collagenase was identified. The evidence is insufficient to

determine the effects of the technology on health outcomes.

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Ongoing and Unpublished Clinical Trials

Some currently unpublished trials that might influence this policy are listed in Table 1.

Table 1. Summary of Key Trials

NCT No. Trial Name Planned

Enrollment

Completion

Date

Ongoing

NCT02301078 Comparing Short-term Function and Pain After Treatment

With Collagenase Clostridium Histolyticum or

Percutaneous Needle Aponeurotomy for Dupuytrens

Disease

60 Nov 2017

(ongoing)

NCT02725528 A Multi-Center, Randomized Controlled Trial Comparing

The Clinical Effectiveness and Cost-Effectiveness of

Collagenase Injection (Xiaflex) and Palmar Fasciectomy in

the Management of Dupuytrens Disease

128 Nov 2018

NCT03000114 Comparison of Collagenase Injection and Percutaneous

Needle Aponeurotomy for Treatment of Dupuytrens

Disease

334 Jan 2021

ISRCTN18254597 Dupuytren's interventions surgery vs collagenase 710 Oct 2021

Unpublished

NCT02193828a

A Phase 2a, Double-blind, Randomized, Placebo-

Controlled, Dose-Ranging Study to Evaluate the Safety and

Effectiveness of AA4500 in the Treatment of Dupuytren's

Disease Nodules

76 Mar 2014

(completed)

NCT02006719a A Randomized, Double-blind, Placebo-controlled Study of

the Safety and Efficacy of AA4500 for the Treatment of

Adhesive Capsulitis of the Shoulder

322 Dec 2014

(completed)

NCT01538017 Comparing Injectable Collagenase (CI) and Percutaneous

Needle Fasciotomy (PNF) for Dupuytren's Contracture (DC)

Affecting Proximal Interphalangeal Joints (PIP). A

Randomised Controlled Trial

50 Nov 2015

(completed)

NCT02267460a

A Phase 3b, Open-label Pilot Study to Evaluate the Safety

and Effectiveness of up to Four Treatment Cycles of

AA4500 in Combination With the ErecAid Esteem

Manual Vacuum Therapy System in Men With Peyronie's

Disease

30 Mar 2016

(completed)

https://clinicaltrials.gov/ct2/show/NCT02301078?term=NCT02301078&rank=1https://clinicaltrials.gov/ct2/show/NCT02725528?term=NCT02725528&rank=1https://clinicaltrials.gov/ct2/show/NCT03000114?term=NCT03000114&rank=1http://www.isrctn.com/ISRCTN18254597https://clinicaltrials.gov/ct2/show/NCT02193828?term=NCT02193828&rank=1https://clinicaltrials.gov/ct2/show/NCT02006719?term=NCT02006719&rank=1https://clinicaltrials.gov/ct2/show/NCT01538017?term=NCT01538017&rank=1https://clinicaltrials.gov/ct2/show/NCT02267460?term=NCT02267460&rank=1

Page | 7 of 13

ISRCTN: International Standard Randomised Controlled Trials Number;

NCT: national clinical trial a Denotes industry-sponsored or cosponsored trial

Clinical Input Received from Physician Specialty Societies and Academic

Medical Centers

While the various physician specialty societies and academic medical centers may provide

appropriate reviewers who collaborate with and make recommendations during this process,

input received does not represent an endorsement or position statement by the physician

specialty societies or academic medical centers, unless otherwise noted.

2011 Input

In response to requests, input was received from 2 physician specialty societies (2 reviews) and 5

academic medical centers (6 reviews) while this policy was under review in 2011. Two reviewers

indicated injectable clostridium collagenase is investigational for the treatment of Dupuytren

contracture, noting lack of long-term data and head-to-head trials comparing collagenase with

surgical options. However, despite considering this treatment investigational due to insufficient

long-term evidence of effectiveness, one reviewer noted that injectable clostridial collagenase

for Dupuytren contracture is approved by the U.S. Food and Drug Administration, and there is

evidence of short-to-medium-term effectiveness available. Five reviewers indicated injectable

clostridial collagenase for Dupuytren contracture may be considered medically necessary. These

reviewers noted this is a treatment alternative to surgery. This was considered to be near-

uniform support for the medical necessity of injectable clostridial collagenase for the treatment

of Dupuytren contracture.

Four reviewers agreed that injectable clostridium collagenase is investigational for the treatment

of Peyronie disease. One of these reviewers also commented that, while this treatment is

considered investigational, it may be indicated for Peyronie disease when it is bothersome,

noting that surgery is intrusive. Four reviewers also agreed injectable clostridium collagenase is

investigational for the treatment of adhesive capsulitis. Finally, 6 reviewers agreed injectable

clostridium collagenase is investigational for all other indications.

Page | 8 of 13

2010 Input

In response to requests, input was received from 6 academic medical centers while this policy

was under review in 2010. The input was mixed, with half of those providing input agreeing that

use of this agent is investigational. While there was support for use in Dupuytren contracture,

comments were made about the limited amount of data on long-term outcomes and durability.

Practice Guidelines and Position Statements

Dupuytren Contracture

National Institute for Health and Care Excellence

In 2017, the National Institute for Health and Care Excellence recommended the use of

collagenase Clostridium histolyticum to treat adults with Dupuytren contracture in cases of

moderate disease where percutaneous needle fasciotomy is not an option.40 The Institute

advised that the decision to use collagenase clostridium rather than limited fasciectomy should

be made only after thorough discussion between the patient and caregiver; the Institute further

defined appropriate outpatient treatment as consisting of a single injection at a time, and

administered by a qualified hand surgeon.

American Urological Association

In 2015, the American Urological Association (AUA) issued a guideline for the diagnosis and

treatment of Peyronie disease.42 For patients with stable Peyronie disease, penile curvature

greater than 30 and less than 90, and intact erectile function (with or without the use of

medications), AUA recommends intralesional collagenase clostridium histolyticum in

combination with modeling (Moderate recommendation; Evidence Strength Grade B).

European Association of Urology

The 2012 European Association of Urology guidelines on penile curvature indicate injectable

collagenase is a treatment option for Peyronie disease based on evidence rated as Level 2b

(Evidence obtained from at least one other type of well-designed quasi-experimental study)

and Grade C (Made despite the absence of directly applicable clinical studies of good

quality).43

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Adhesive Capsulitis

National Institute for Health Research

In 2012, the National Institute for Health Research published a health technology assessment

(HTA) on the management of adhesive capsulitis.44 In this assessment, collagenase injections

were not included in the treatments considered for adhesive capsulitis.

Medicare National Coverage

There is no national coverage determination (NCD). In the absence of an NCD, coverage

decisions are left to the discretion of local Medicare carriers.

Regulatory Status

Table 2 lists indications for clostridial collagenase (Xiaflex; Auxilium Pharmaceuticals

[Norristown, PA]) that have been approved by the Food and Drug Administration.

Table 2. FDA-Approval History For Clostridial Collagenase (Xiaflex)3

Indication Approved Initial Indication Additional Information

Dupuytren

contracture

2010 Treatment of adult patients with

Dupuytren contracture with a

palpable cord

Up to 3 injections at 4-week

intervals may be given into a

palpable Dupuytren cord with a

contracture of a

metacarpophalangeal joint or a

proximal interphalangeal joint

Approval accompanied by REMS. The

manufacturer must:

o Evaluate and mitigate risks and serious

adverse events

o Instruct health care providers on

procedure to inject Xiaflex and perform

finger extension procedures

o Inform patients of potential risks of

treatment

In 2014, indication expanded: up to 2

joints in the same hand may be treated

during a treatment visit

Peyronie

disease

2013 Treatment of men with a

palpable penile plaque and

penile curvature more than 30

degrees

Treatment course consists of a

maximum of 4 cycles, each of

Approval accompanied by black box

warning of corporal rupture

Only available through a restricted

program, Xiaflex REMS, due to risk of

corporal rupture. REMS requirements:

o Prescribers must enroll and complete

Page | 10 of 13

Indication Approved Initial Indication Additional Information

which consists of 2 Xiaflex

injection procedures

training in the administration of Xiaflex

for the treatment of Peyronie disease

o Health care sites must be certified with

the program and ensure that only

certified prescribers administer Xiaflex

Adapted from Food and Drug Administration (2017).3

FDA: Food and Drug Administration; REMS: Risk Evaluation and Mitigation Strategy

References

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2. Hellstrom WJ. Medical management of Peyronie's disease. J Androl. Jul-Aug 2009;30(4):397-405. PMID 18974422

3. Food and Drug Administration (FDA). Xiaflex: Label. 2017; Available at:

https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/125338s0061lbl.pdf Accessed January 2018.

4. Smeraglia F, Del Buono A, Maffulli N. Collagenase clostridium histolyticum in Dupuytren's contracture: a systematic review. Br

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6. Chen NC, Srinivasan RC, Shauver MJ, et al. A systematic review of outcomes of fasciotomy, aponeurotomy, and collagenase

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7. Peimer CA, Wilbrand S, Gerber RA, et al. Safety and tolerability of collagenase Clostridium histolyticum and fasciectomy for

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8. Hurst LC, Badalamente MA, Hentz VR, et al. Injectable collagenase clostridium histolyticum for Dupuytren's contracture. N Engl J

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9. Witthaut J, Bushmakin AG, Gerber RA, et al. Determining clinically important changes in range of motion in patients with

Dupuytren's Contracture: secondary analysis of the randomized, double-blind, placebo-controlled CORD I study. Clin Drug

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10. Holzer LA, Holzer G. Injectable collagenase clostridium histolyticum for Dupuytren's contracture. N Engl J Med. Dec 24

2009;361(26):2579; author reply 2579-2580. PMID 20050321

11. Gilpin D, Coleman S, Hall S, et al. Injectable collagenase Clostridium histolyticum: a new nonsurgical treatment for Dupuytren's

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12. McGrouther DA, Jenkins A, Brown S, et al. The efficacy and safety of collagenase clostridium histolyticum in the treatment of

patients with moderate Dupuytren's contracture. Curr Med Res Opin. Apr 2014;30(4):733-739. PMID 24397625

13. Badalamente MA, Hurst LC. Efficacy and safety of injectable mixed collagenase subtypes in the treatment of Dupuytren's

contracture. J Hand Surg Am. Jul-Aug 2007;32(6):767-774. PMID 17606053

14. Raven RB, 3rd, Kushner H, Nguyen D, et al. Analysis of efficacy and safety of treatment with collagenase Clostridium

histolyticum among subgroups of patients with Dupuytren contracture. Ann Plast Surg. Sep 2014;73(3):286-290. PMID

23511746

https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/125338s0061lbl.pdf

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15. Naam NH. Functional outcome of collagenase injections compared with fasciectomy in treatment of Dupuytren's contracture.

Hand (N Y). Dec 2013;8(4):410-416. PMID 24426958

16. Povlsen B, Povlsen SD. What is the better treatment for single digit Dupuytren's contracture: surgical release or collagenase

clostridium histolyticum (Xiapex) injection? Hand Surg. Aug 25 2014:1-4. PMID 25155703

17. Zhou C, Hovius SE, Slijper HP, et al. Collagenase Clostridium histolyticum versus limited fasciectomy for dupuytren's

contracture: outcomes from a multicenter propensity score matched study. Plast Reconstr Surg. Jul 2015;136(1):87-97. PMID

25829153

18. Witthaut J, Jones G, Skrepnik N, et al. Efficacy and safety of collagenase clostridium histolyticum injection for Dupuytren

contracture: short-term results from 2 open-label studies. J Hand Surg Am. Jan 2013;38(1):2-11. PMID 23218556

19. Peimer CA, Blazar P, Coleman S, et al. Dupuytren contracture recurrence following treatment with collagenase clostridium

histolyticum (CORDLESS study): 3-year data. J Hand Surg Am. Jan 2013;38(1):12-22. PMID 23200951

20. Peimer CA, Blazar P, Coleman S, et al. Dupuytren contracture recurrence following treatment with Collagenase Clostridium

histolyticum (CORDLESS [Collagenase Option for Reduction of Dupuytren Long-Term Evaluation of Safety Study]): 5-Year Data.

J Hand Surg. Aug 2015;40(8):1597-1605. PMID 26096221

21. Badalamente MA, Hurst LC, Benhaim P, et al. Efficacy and safety of collagenase clostridium histolyticum in the treatment of

proximal interphalangeal joints in dupuytren contracture: combined analysis of 4 phase 3 clinical trials. J Hand Surg. May

2015;40(5):975-983. PMID 25843533

22. Gaston RG, Larsen SE, Pess GM, et al. efficacy and safety of concurrent collagenase clostridium histolyticum injections for 2

dupuytren contractures in the same hand: a prospective, multicenter study. J Hand Surg. Oct 2015;40(10):1963-1971. PMID

26216077

23. Watt AJ, Curtin CM, Hentz VR. Collagenase injection as nonsurgical treatment of Dupuytren's disease: 8-year follow-up. J Hand

Surg Am. Apr 2010;35(4):534-539, 539 e531. PMID 20353858

24. Alberton F, Corain M, Garofano A, et al. Efficacy and safety of collagenase Clostridium histolyticum injection for Dupuytren

contracture: report of 40 cases. Musculoskelet Surg. Dec 2014;98(3):225-232. PMID 24254968

25. Warwick D, Arner M, Pajardi G, et al. Collagenase clostridium histolyticum in patients with Dupuytren's contracture: results from

POINT X, an open-label study of clinical and patient-reported outcomes. J Hand Surg Eur Vol. Feb 2015;40(2):124-132. PMID

24470559

26. Verheyden JR. Early outcomes of a sequential series of 144 patients with Dupuytren's contracture treated by collagenase

injection using an increased dose, multi-cord technique. J Hand Surg Eur Vol. Feb 2015;40(2):133-140. PMID 24698852

27. McMahon HA, Bachoura A, Jacoby SM, et al. Examining the efficacy and maintenance of contracture correction after

collagenase clostridium histolyticum treatment for Dupuytren's disease. Hand (N Y). Sep 2013;8(3):261-266. PMID 24426932

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29. Atroshi I, Nordenskjold J, Lauritzson A, et al. Collagenase treatment of Dupuytren's contracture using a modified injection

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34. Gelbard M, Goldstein I, Hellstrom WJ, et al. Clinical efficacy, safety and tolerability of collagenase clostridium histolyticum for

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2013;190(1):199-207. PMID 23376148

35. Lipshultz LI, Goldstein I, Seftel AD, et al. Clinical efficacy of collagenase Clostridium histolyticum in the treatment of Peyronie's

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History

Date Comments 11/11/13 New Policy. Policy replaces 5.01.524. Considered medically necessary to treat

Dupuytrens contracture in adult patients when criteria are met.

12/17/14 Annual Review. Policy updated with literature review through September 5, 2014.

References 3, 5, 10, 13-14, 17-22, 27 added; others renumbered/removed. Rationale

section reorganized. Policy statements unchanged. ICD-9 and ICD-10 diagnosis and

procedure codes removed; these do not relate to policy adjudication.

12/08/15 Annual Review. Policy updated with literature review through September 10, 2015;

references 16, 19-21, 28, 33, 35, and 37-38 added. Policy statements unchanged.

https://www.nice.org.uk/guidance/TA459/chapter/1-Recommendationshttp://www.auanet.org/guidelines/peyronies-disease-(2015)

Page | 13 of 13

Date Comments 12/01/16 Annual Review, approved November 8, 2016. Policy updated with literature review

through August 2016; references added. Policy statements unchanged.

12/01/17 Annual Review, approved November 9, 2017. Policy updated with literature review

through October 2017. Reference added. Policy statements unchanged.

02/01/18 Annual Review, approved January 30, 2018. Policy updated with literature review

through November, 2017; reference 40 added. Policy statements unchanged.

Disclaimer: This medical policy is a guide in evaluating the medical necessity of a particular service or treatment. The

Company adopts policies after careful review of published peer-reviewed scientific literature, national guidelines and

local standards of practice. Since medical technology is constantly changing, the Company reserves the right to review

and update policies as appropriate. Member contracts differ in their benefits. Always consult the member benefit

booklet or contact a member service representative to determine coverage for a specific medical service or supply.

CPT codes, descriptions and materials are copyrighted by the American Medical Association (AMA). 2018 Premera

All Rights Reserved.

Scope: Medical policies are systematically developed guidelines that serve as a resource for Company staff when

determining coverage for specific medical procedures, drugs or devices. Coverage for medical services is subject to

the limits and conditions of the member benefit plan. Members and their providers should consult the member

benefit booklet or contact a customer service representative to determine whether there are any benefit limitations

applicable to this service or supply. This medical policy does not apply to Medicare Advantage.

037338 (07-2016)

Discrimination is Against the Law Premera Blue Cross complies with applicable Federal civil rights laws and does not discriminate on the basis of race, color, national origin, age, disability, or sex. Premera does not exclude people or treat them differently because of race, color, national origin, age, disability or sex. Premera: Provides free aids and services to people with disabilities to communicate

effectively with us, such as: Qualified sign language interpreters Written information in other formats (large print, audio, accessible

electronic formats, other formats) Provides free language services to people whose primary language is not

English, such as: Qualified interpreters Information written in other languages

If you need these services, contact the Civil Rights Coordinator. If you believe that Premera has failed to provide these services or discriminated in another way on the basis of race, color, national origin, age, disability, or sex, you can file a grievance with: Civil Rights Coordinator - Complaints and Appeals PO Box 91102, Seattle, WA 98111 Toll free 855-332-4535, Fax 425-918-5592, TTY 800-842-5357 Email AppealsDepartmentInquiries@Premera.com You can file a grievance in person or by mail, fax, or email. If you need help filing a grievance, the Civil Rights Coordinator is available to help you. You can also file a civil rights complaint with the U.S. Department of Health and Human Services, Office for Civil Rights, electronically through the Office for Civil Rights Complaint Portal, available at https://ocrportal.hhs.gov/ocr/portal/lobby.jsf, or by mail or phone at: U.S. Department of Health and Human Services 200 Independence Avenue SW, Room 509F, HHH Building Washington, D.C. 20201, 1-800-368-1019, 800-537-7697 (TDD) Complaint forms are available at http://www.hhs.gov/ocr/office/file/index.html. Getting Help in Other Languages This Notice has Important Information. This notice may have important information about your application or coverage through Premera Blue Cross. There may be key dates in this notice. You may need to take action by certain deadlines to keep your health coverage or help with costs. You have the right to get this information and help in your language at no cost. Call 800-722-1471 (TTY: 800-842-5357). (Amharic): Premera Blue Cross 800-722-1471 (TTY: 800-842-5357)

:(Arabic) .

Premera Blue Cross. . . . (TTY: 800-842-5357) 1471-722-800

(Chinese): Premera Blue Cross

800-722-1471 (TTY: 800-842-5357)

Oromoo (Cushite): Beeksisni kun odeeffannoo barbaachisaa qaba. Beeksisti kun sagantaa yookan karaa Premera Blue Cross tiin tajaajila keessan ilaalchisee odeeffannoo barbaachisaa qabaachuu dandaa. Guyyaawwan murteessaa taan beeksisa kana keessatti ilaalaa. Tarii kaffaltiidhaan deeggaramuuf yookan tajaajila fayyaa keessaniif guyyaa dhumaa irratti wanti raawwattan jiraachuu dandaa. Kaffaltii irraa bilisa haala taeen afaan keessaniin odeeffannoo argachuu fi deeggarsa argachuuf mirga ni qabaattu. Lakkoofsa bilbilaa 800-722-1471 (TTY: 800-842-5357) tii bilbilaa. Franais (French): Cet avis a d'importantes informations. Cet avis peut avoir d'importantes informations sur votre demande ou la couverture par l'intermdiaire de Premera Blue Cross. Le prsent avis peut contenir des dates cls. Vous devrez peut-tre prendre des mesures par certains dlais pour maintenir votre couverture de sant ou d'aide avec les cots. Vous avez le droit d'obtenir cette information et de laide dans votre langue aucun cot. Appelez le 800-722-1471 (TTY: 800-842-5357). Kreyl ayisyen (Creole): Avi sila a gen Enfmasyon Enptan ladann. Avi sila a kapab genyen enfmasyon enptan konsnan aplikasyon w lan oswa konsnan kouvti asirans lan atrav Premera Blue Cross. Kapab genyen dat ki enptan nan avi sila a. Ou ka gen pou pran kk aksyon avan sten dat limit pou ka kenbe kouvti asirans sante w la oswa pou yo ka ede w avk depans yo. Se dwa w pou resevwa enfmasyon sa a ak asistans nan lang ou pale a, san ou pa gen pou peye pou sa. Rele nan 800-722-1471 (TTY: 800-842-5357). Deutsche (German): Diese Benachrichtigung enthlt wichtige Informationen. Diese Benachrichtigung enthlt unter Umstnden wichtige Informationen bezglich Ihres Antrags auf Krankenversicherungsschutz durch Premera Blue Cross. Suchen Sie nach eventuellen wichtigen Terminen in dieser Benachrichtigung. Sie knnten bis zu bestimmten Stichtagen handeln mssen, um Ihren Krankenversicherungsschutz oder Hilfe mit den Kosten zu behalten. Sie haben das Recht, kostenlose Hilfe und Informationen in Ihrer Sprache zu erhalten. Rufen Sie an unter 800-722-1471 (TTY: 800-842-5357). Hmoob (Hmong): Tsab ntawv tshaj xo no muaj cov ntshiab lus tseem ceeb. Tej zaum tsab ntawv tshaj xo no muaj cov ntsiab lus tseem ceeb txog koj daim ntawv thov kev pab los yog koj qhov kev pab cuam los ntawm Premera Blue Cross. Tej zaum muaj cov hnub tseem ceeb uas sau rau hauv daim ntawv no. Tej zaum koj kuj yuav tau ua qee yam uas peb kom koj ua tsis pub dhau cov caij nyoog uas teev tseg rau hauv daim ntawv no mas koj thiaj yuav tau txais kev pab cuam kho mob los yog kev pab them tej nqi kho mob ntawd. Koj muaj cai kom lawv muab cov ntshiab lus no uas tau muab sau ua koj hom lus pub dawb rau koj. Hu rau 800-722-1471 (TTY: 800-842-5357). Iloko (Ilocano): Daytoy a Pakdaar ket naglaon iti Napateg nga Impormasion. Daytoy a pakdaar mabalin nga adda ket naglaon iti napateg nga impormasion maipanggep iti apliksayonyo wenno coverage babaen iti Premera Blue Cross. Daytoy ket mabalin dagiti importante a petsa iti daytoy a pakdaar. Mabalin nga adda rumbeng nga aramidenyo nga addang sakbay dagiti partikular a naituding nga aldaw tapno mapagtalinaedyo ti coverage ti salun-atyo wenno tulong kadagiti gastos. Adda karbenganyo a mangala iti daytoy nga impormasion ken tulong iti bukodyo a pagsasao nga awan ti bayadanyo. Tumawag iti numero nga 800-722-1471 (TTY: 800-842-5357). Italiano (Italian): Questo avviso contiene informazioni importanti. Questo avviso pu contenere informazioni importanti sulla tua domanda o copertura attraverso Premera Blue Cross. Potrebbero esserci date chiave in questo avviso. Potrebbe essere necessario un tuo intervento entro una scadenza determinata per consentirti di mantenere la tua copertura o sovvenzione. Hai il diritto di ottenere queste informazioni e assistenza nella tua lingua gratuitamente. Chiama 800-722-1471 (TTY: 800-842-5357).

(Japanese): Premera Blue Cross

800-722-1471 (TTY: 800-842-5357) (Korean): . Premera Blue Cross . . . . 800-722-1471 (TTY: 800-842-5357) . (Lao): . Premera Blue Cross. . . . 800-722-1471 (TTY: 800-842-5357). (Khmer):

Premera Blue Cross

800-722-1471 (TTY: 800-842-5357) (Punjabi): . Premera Blue Cross . . , , 800-722-1471 (TTY: 800-842-5357).

:(Farsi) .

. Premera Blue Cross .

. .

)800-842-5357 TTY( 800-722-1471 .

Polskie (Polish): To ogoszenie moe zawiera wane informacje. To ogoszenie moe zawiera wane informacje odnonie Pastwa wniosku lub zakresu wiadcze poprzez Premera Blue Cross. Prosimy zwrcic uwag na kluczowe daty, ktre mog by zawarte w tym ogoszeniu aby nie przekroczy terminw w przypadku utrzymania polisy ubezpieczeniowej lub pomocy zwizanej z kosztami. Macie Pastwo prawo do bezpatnej informacji we wasnym jzyku. Zadzwocie pod 800-722-1471 (TTY: 800-842-5357). Portugus (Portuguese): Este aviso contm informaes importantes. Este aviso poder conter informaes importantes a respeito de sua aplicao ou cobertura por meio do Premera Blue Cross. Podero existir datas importantes neste aviso. Talvez seja necessrio que voc tome providncias dentro de determinados prazos para manter sua cobertura de sade ou ajuda de custos. Voc tem o direito de obter esta informao e ajuda em seu idioma e sem custos. Ligue para 800-722-1471 (TTY: 800-842-5357).

Romn (Romanian): Prezenta notificare conine informaii importante. Aceast notificare poate conine informaii importante privind cererea sau acoperirea asigurrii dumneavoastre de sntate prin Premera Blue Cross. Pot exista date cheie n aceast notificare. Este posibil s fie nevoie s acionai pn la anumite termene limit pentru a v menine acoperirea asigurrii de sntate sau asistena privitoare la costuri. Avei dreptul de a obine gratuit aceste informaii i ajutor n limba dumneavoastr. Sunai la 800-722-1471 (TTY: 800-842-5357). P (Russian): . Premera Blue Cross. . , , . . 800-722-1471 (TTY: 800-842-5357). Faasamoa (Samoan): Atonu ua iai i lenei faasilasilaga ni faamatalaga e sili ona taua e tatau ona e malamalama i ai. O lenei faasilasilaga o se fesoasoani e faamatala atili i ai i le tulaga o le polokalame, Premera Blue Cross, ua e tau fia maua atu i ai. Faamolemole, ia e iloilo faalelei i aso faapitoa oloo iai i lenei faasilasilaga taua. Masalo o lea iai ni feau e tatau ona e faia ao lei aulia le aso ua taua i lenei faasilasilaga ina ia e iai pea ma maua fesoasoani mai ai i le polokalame a le Malo oloo e iai i ai. Oloo iai iate oe le aia tatau e maua atu i lenei faasilasilaga ma lenei famatalaga i legagana e te malamalama i ai aunoa ma se togiga tupe. Vili atu i le telefoni 800-722-1471 (TTY: 800-842-5357). Espaol (Spanish): Este Aviso contiene informacin importante. Es posible que este aviso contenga informacin importante acerca de su solicitud o cobertura a travs de Premera Blue Cross. Es posible que haya fechas clave en este aviso. Es posible que deba tomar alguna medida antes de determinadas fechas para mantener su cobertura mdica o ayuda con los costos. Usted tiene derecho a recibir esta informacin y ayuda en su idioma sin costo alguno. Llame al 800-722-1471 (TTY: 800-842-5357). Tagalog (Tagalog): Ang Paunawa na ito ay naglalaman ng mahalagang impormasyon. Ang paunawa na ito ay maaaring naglalaman ng mahalagang impormasyon tungkol sa iyong aplikasyon o pagsakop sa pamamagitan ng Premera Blue Cross. Maaaring may mga mahalagang petsa dito sa paunawa. Maaring mangailangan ka na magsagawa ng hakbang sa ilang mga itinakdang panahon upang mapanatili ang iyong pagsakop sa kalusugan o tulong na walang gastos. May karapatan ka na makakuha ng ganitong impormasyon at tulong sa iyong wika ng walang gastos. Tumawag sa 800-722-1471 (TTY: 800-842-5357). (Thai): Premera Blue Cross 800-722-1471 (TTY: 800-842-5357) (Ukrainian): . Premera Blue Cross. , . , , . . 800-722-1471 (TTY: 800-842-5357). Ting Vit (Vietnamese): Thng bo ny cung cp thng tin quan trng. Thng bo ny c thng tin quan trng v n xin tham gia hoc hp ng bo him ca qu v qua chng trnh Premera Blue Cross. Xin xem ngy quan trng trong thng bo ny. Qu v c th phi thc hin theo thng bo ng trong thi hn duy tr bo him sc khe hoc c tr gip thm v chi ph. Qu v c quyn c bit thng tin ny v c tr gip bng ngn ng ca mnh min ph. Xin gi s 800-722-1471 (TTY: 800-842-5357).