SAFETY

 

To report an Adverse Event, submit a Medical Device Report, or other safety finding or Product Complaint call, 1-800-453-6948 or email: PatientSafety@vcel.com

 

Adverse Reactions

The most frequently occurring adverse reactions (≥5%) reported for MACI were arthralgia, tendonitis, back pain, joint swelling, and joint effusion.

Serious adverse reactions reported for MACI were arthralgia, cartilage injury, meniscus injury, treatment failure, and osteoarthritis.
 

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a product cannot be directly compared to rates in the clinical trials of another product and may not reflect the rates observed in practice.

In a 2-year prospective, multicenter, randomized, open-label, parallel-group clinical trial1, 144 patients, ages 18 to 54 years, were randomized to receive a 1-time treatment with MACI or microfracture (1:1, 72 patients in each treatment group). Demographic characteristics of patients in the trial were similar in both treatment groups. The majority of patients were male (62.5% MACI, 66.7% microfracture), and the mean ages were 34.8 (MACI) and 32.9 (microfracture) years. Overall, 70 patients in the MACI group and 67 patients in the microfracture group completed 2 years of follow-up.

In addition, all 144 subjects from the 2-year clinical trial had the option to enroll in a 3-year  follow-up study (extension study).  Safety and efficacy assessments were performed at yearly scheduled visits.  The demographic characteristics of patients (N = 128) enrolled in the extension study were similar in both treatment groups and consistent with the overall population of the 2-year clinical trial.

The proportion of patients with at least 1 subsequent surgical procedure (any surgical procedure performed on the treated knee joint, including arthroscopy, arthrotomy, or manipulation under anesthesia) in the 2 years following study treatment was comparable between treatment groups (8.3% in the MACI group and 9.7% in the microfracture group).

Adverse reactions reported in ≥5% of patients in either treatment group in the 2‑year clinical trial are provided in Table 1.
 

Table 1. Adverse Reactions in ≥5% of Patients in Any Treatment Group in the 2-Year Clinical Trial

 

In the 3-year extension study, adverse reactions reported in ≥5% of patients were (MACI vs microfracture):  arthralgia (46.2% vs 50.8%), tendonitis (6.2% vs 1.6%), back pain (4.6% vs 6.3%), osteoarthritis (4.6% vs 7.9%), joint effusion (3.1% vs 7.9%), cartilage injury (6.2% vs 15.9%), procedural pain (3.1% vs 7.9%), ligament sprain (1.5% vs 7.9%), and treatment failure (4.6% vs 7.9%).

Serious adverse reactions reported in patients in either treatment group for integrated data across the 2-year clinical trial and the 3-year extension study are provided in Table 2.
 

Table 2. Serious Adverse Reactions in Patients in Any Treatment Group Across the 2‑Year Clinical Trial and the 3-Year Extension Study

 

Postmarketing Experience

Graft complication (e.g., abnormalities to the repair graft that become symptomatic; this could include graft overgrowth [tissue hypertrophy], under-fill or damage to the repair tissue that has elicited a painful response, or mechanical symptoms), graft delamination  (i.e., a dislodging of the repair graft from the underlying subchondral bone that has become symptomatic; this can be measured as marginal, partial, or a complete delaminated graft), and tendonitis have been reported during use of MACI outside the United States. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to MACI exposure.

 

1. Saris D, Price A, Widuchowski W, et al. Matrix-applied characterized autologous cultured chondrocytes versus microfracture: Two-year follow-up of a prospective randomized trial. Am J Sports Med. 2014;42(6):1384-94.