Micafungin Effective for Serious Candida Infections

COLOGNE, Germany, April 26 -- For treating candidemia and invasive candidosis, micafungin (Mycamine) is as effective as liposomal amphotericin B, according to researchers here.

But in a randomized, double-blind head-to-head trial, micafungin had fewer adverse effects than amphotericin, found Oliver Cornely, M.D., of University Hospital of Cologne, and colleagues.

The results of the industry-sponsored non-inferiority trial "establish micafungin as a treatment option for first-line therapy of candidemia and invasive candidosis," they reported online in The Lancet.

Micafungin is approved in the U.S. for esophageal candidiasis and to prevent Candida infections in patients undergoing a stem-cell transplant but it has not been approved for bloodstream or invasive infections.

The range of treatments for these more serious infections has been increasing, Dr. Cornely and colleagues said, and includes liposomal amphotericin B, marketed as Ambisome.

The researchers enrolled 531 patients from 115 study sites in Europe, India, Brazil, North America, Thailand, South Africa, and Australia. They were eligible for the trial if they were at least 16, had clinical signs of systemic Candida infection, and had one or more positive cultures from blood or another sterile site within the previous four days.

The study compared 100 mg/day of micafungin to 3 mg/kg of body weight of liposomal amphotericin B. In cases of non-response after five days, the dose could be increased to 200 mg/day for micafungin and 5 mg/kg for liposomal amphotericin B. Dosage could also be reduced in response to adverse events.

The results were analyzed on a per-protocol basis, but the researchers also considered an intent-to-treat population (patients who got at least one dose of study drug) and a modified intent-to-treat group (at least one dose of study drug and a confirmed Candida infection at baseline.)

In all three analyses, Dr. Cornely and colleagues said, efficacy was almost identical between the arms. Specifically:

• In the per-protocol population, 89.6% of micafungin patients were treated successfully compared to 89.5% of those given liposomal amphotericin B.
• In the modified intent-to-treat group, the corresponding rates were 74.1% and 69.6%.
• In the intent-to-treat population, the success rates were 71.6% (189 of 264 micafungin patients) and 68.2% (182 of 267 patients treated with liposomal amphotericin B.)

Treatment success was defined as a complete or partial resolution of symptoms, with complete eradication of the fungus.

Most patients had candidemia, and the success rates were 90.6% with micafungin and 90.8% with liposomal amphotericin B. For those who had invasive disease, the overall success rate for micafungin was 84.4% (27 of the 32 cases successfully treated) and 81.5% (22 of 27 cases successfully treated) for liposomal amphotericin B.

Serious adverse events and discontinuations owing to such events were higher for liposomal amphotericin B, although not significantly so, the researchers reported.

However, some events were significantly more common in the liposomal amphotericin B arm:

• Rigors were seen in two micafungin patients (0.8%), compared to 17 (6.4%) liposomal amphotericin B patients, a difference that was significant at P= 0.0006.
• Increased serum creatinine was seen in five micafungin patients (1.9%) and 17 (6.4%) liposomal amphotericin B patients, which was significant at P=0.015.
• One micafungin patient (0.4%) reported back pain, compared to 12 (4.5%) of the liposomal amphotericin B patients, which was significant at P=0.003
• An infusion-related reaction was seen in 45 micafungin patients (17.0%) and 77 liposomal amphotericin B patients (28.8%), a difference that was significant at P=0.001.

Dr. Cornely reports receiving consulting or lecture fees from Astellas Pharma GmbH, as do Ernst-Rdiger Kuse, M.D., Olivier Lortholary, M.D., and Andrew J. Ullmann, M.D. Luis Ostrosky-Zeichner, M.D., received lecture fees and a research grant from the company that was relevant to the study. Dr. Ullmann has also received research funding from Schering-Plough, has acted as a consultant to Schering-Plough, MSD, Basilea, Pfizer, Gilead, and Stiefel, and has acted on speakers' bureau for Gilead, MSD, Pfizer, and Schering-Plough. Sonja Koblinger, M.D., and Heike Diekmann-Berndt, Ph.D., are employees of Astellas Pharma GmbH. All other authors declare that they have no conflict of interest.