This policy version was replaced January 30, 2023. To find the newest version, go to https://www.bluecrossmn.com/providers/medical-policy-and-utilization-management, read and accept the Blue Cross Medical Policy Statement, then select “Blue Cross and Blue Shield of Minnesota Medical Policies.” This will bring up the Medical Policy search screen. Enter the policy number without the version number (last 3 digits).

Collagenases are enzymes that break down collagen and may be used for nonsurgical treatment of fibroproliferative disorders characterized by excessive collagen deposits. Clostridial collagenase is a combination of two microbial collagenases derived from Clostridium histolyticum bacteria. Injection of clostridial collagenase into a Dupuytren’s cord or a Peyronie’s plaque, which are comprised mostly of collagen, may result in disruption of the cord or plaque.

The U.S. Food and Drug Administration (FDA) has approved injectable clostridial collagenase (Xiaflex®) for treatment of adults with the following conditions:

• Dupuytren’s contracture with a palpable cord.
• Peyronie’s disease with a palpable plaque and curvature deformity of at least 30 degrees at the start of therapy.

The FDA has approved another collagenase product known as collagenase clostridium histolyticum (Qwo™). Qwo™ is FDA approved for the treatment of moderate to severe cellulite in the buttocks of adult women.

Serious adverse reactions have occurred in patients receiving injectable clostridial collagenase, including tendon rupture, corporal rupture (penile fracture), and other serious injury to the injected finger, hand, or penis. Due to these safety concerns, the FDA regulates injectable clostridial collagenase for the treatment of Peyronie’s disease through a restricted distribution program under a risk evaluation and mitigation strategy (REMS) called the Xiaflex REMS Program. Under the REMS, only certified healthcare facilities can administer injectable clostridial collagenase. The prescribing information for injectable clostridial collagenase also includes a black box warning.

I.    Injectable clostridial collagenase may be considered MEDICALLY NECESSARY AND APPROPRIATE when ALL of the following criteria are met:

• Age 18 years or older; AND
• ONE of the following:
  • Diagnosis of Dupuytren’s contracture AND ALL of the following:
    1. There is a palpable cord; AND
    2. The contracture measures ≥20 degrees at either the metacarpophalangeal (MCP) joint or the proximal interphalangeal (PIP) joint (excluding the thumb); AND
    3. No more than 3 injections per cord at intervals not less than 4 weeks; AND
    4. No more than 2 cords or joints in the same hand are treated during a treatment visit; OR
  • Diagnosis of Peyronie’s disease AND ALL of the following:
    1. There is a palpable plaque causing curvature deformity; AND
    2. The curvature deformity measures ≥30 degrees at the start of therapy; AND
    3. No more than 2 injections per plaque, 1-3 days apart, per treatment cycle; AND
    4. No more than 4 treatment cycles (8 injections total) per plaque at intervals not less than 6 weeks between treatment cycles; AND
    5. If the curvature deformity is <15 degrees after the first, second, or third treatment cycle, subsequent treatment cycles will not be administered; 
• AND
• No FDA labeled contraindications to therapy (see table below).

II.   Injections of clostridial collagenase for Dupuytren's contracture or Peyronie’s disease beyond that described above are considered EXPERIMENTAL/INVESTIGATIVE due to the lack of clinical evidence demonstrating an impact on improved health outcomes.

III.  Injectable clostridial collagenase is considered EXPERIMENTAL/INVESTIGATIVE for all other indications, including but not limited to adhesive capsulitis, due to the lack of clinical evidence demonstrating an impact on improved health outcomes.

IV.  The use of injectable clostridial collagenase is considered COSMETIC for the treatment of cellulite and other indications solely to improve appearance.

        Table. FDA-Labeled Contraindications