Early studies demonstrated that treatment with ACTIMMUNE® significantly reduced the number of serious infections in patients with Chronic Granulomatous Disease, a rare congenital disorder characterized by a defect in immune cells called phagocytes.1 Since osteoclasts dissolve bone debris by the same mechanism that phagocytes kill ingested bacteria, researchers hypothesized that ACTIMMUNE® might also enhance the function of osteoclasts in patients with osteopetrosis.2
Three clinical studies have assessed the efficacy and safety of ACTIMMUNE® in patients with osteopetrosis. In the first study, 8 patients were treated with ACTIMMUNE® 1.5 mcg/kg three times per week for six months. During the treatment period, all patients demonstrated significant increases in bone marrow production and bone resorption, as well as a reduction in the number of serious infections.2
The second study evaluated the effect of treatment in 14 patients (including 8 patients from the previous study) who received ACTIMMUNE® 1.5 mcg/kg three times per week for at least six months. Following treatment, researchers observed statistically significant increases in markers of bone resorption that corresponded with reductions in trabecular bone volume and increased bone marrow space. Patients who were treated for 18 months (n=11) continued to show improvements in bone resorption and bone marrow activity, as well as a decrease in the frequency of serious infections. Side effects, while common, were characterized by the investigators as mild and transient, and no patient required discontinuation of therapy due to toxicity.3
Figure 1. Change in bone density following treatment with Actimmune®. Adapted from Key et al., 1995.
In the third study, 16 patients with severe malignant osteopetrosis were randomized to receive either ACTIMMUNE® plus calcitriol or calcitriol alone. Patients were monitored for evidence of disease progression, which was defined as any of the following: 1) death; 2) significant decline in hemoglobin or platelet counts; 3) serious infection requiring antibiotic therapy; or 4) decrease in hearing or vision.
At the conclusion of the study, investigators observed a significant delay in the time to disease progression among patients in the ACTIMMUNE® treatment group. The mean time to disease progression was 452 days in patients treated with ACTIMMUNE® plus calcitriol, compared with 129 days in patients treated with calcitriol alone. Additionally, fewer patients in the ACTIMMUNE® treatment group experienced serious infections compared with those receiving calcitriol alone (10% vs. 67%).4
Finally, in an analysis that combined data from a second study, 19 of 24 patients treated with ACTIMMUNE® with or without calcitriol for at least six months had reduced trabecular bone volume compared to baseline.5
- Click here to learn more about ACTIMMUNE® safety
The most common adverse events observed in patients receiving Actimmune® were flu-like symptoms (e.g., headache, fatigue, fever, myalgia, and rigors). Please refer to the ACTIMMUNE® Safety section on this Web site for more complete safety information. 5
The health information contained herein is provided for educational purposes only and is not intended to replace discussions with a healthcare provider. All decisions regarding patient care must be made with a healthcare provider, considering the unique characteristics of patients.
For U.S. resident use only. The product discussed herein may have different product labeling in different countries. Please refer to the full U.S. Prescribing Information (pdf file).
References
1. The International Chronic Granulomatous Disease Cooperative Study Group. A controlled trial of interferon gamma to prevent infection in chronic granulomatous disease. N Engl J Med. 1991; 324: 509-516.
2. Key LL, Ries WL, Rodriguiz RM, Hatcher HC. Recombinant human interferon gamma for osteopetrosis. J Pediatrics. 1992;121:119-124.
3. Key LL Jr, Rodriguiz RM, Willi SM, et al. Long-term treatment of osteopetrosis with recombinant human interferon gamma. N Engl J Med. 1995;24:1594-1599.
4. Key LL. A phase III randomized controlled open-label trial of Interferon-gamma-1b in patients with severe congenital (malignant) osteopetrosis. J Bone Min Res. 2004;19:1372.
5. ACTIMMUNE® [package insert]. Brisbane, Calif: InterMune, Inc.; 2005.
