Assessment of survival in a 2-year comparative study of lanthanum carbonate versus standard therapy

Abstract

Objective:

Epidemiological data link elevated levels of serum phosphorus with increased mortality among patients with chronic kidney disease. Recent data also suggest improved survival with the use of dietary phosphate binders in patients on dialysis. However, few studies have comprehensively evaluated the survival benefit associated with different phosphate binders. A post-hoc survival analysis was undertaken of lanthanum carbonate (Fosrenol

*Fosrenol is a registered trademark of Shire Pharmaceuticals, Basingstoke, UK.

) versus standard therapy.

Research design and methods:

Patients on dialysis enrolled in a phase 3, 2-year, comparative safety study were randomized 1:1 to lanthanum carbonate or standard therapy to treat serum phosphorus to a target of ≤5.9 mg/dL (1.90 mmol/L). Patients (N = 1354) were followed up for survival status during, or after completion of or discontinuation from the study.

Main outcome measures:

Survival was measured by time from first dose of study medication to all-cause mortality or last contact.

Results:

The distribution of follow-up time was similar in the lanthanum carbonate and standard therapy groups (mean 23.7 versus 23.9 months [median 27.0 versus 26.0 months], respectively). Serum phosphorus levels were similar across treatment groups, as patients were treated to target. At follow-up, 19.9% (135/680) of patients treated with lanthanum carbonate had died versus 23.3% (157/674) on standard therapy (log-rank p = 0.18). In the subgroup of patients aged >65 years (n = 336), 27.0% (44/163) of lanthanum-carbonate-treated patients had died compared with 39.3% (68/173) on standard therapy (log-rank p = 0.04).

Conclusion:

In these survival analyses, overall mortality was similar in the lanthanum carbonate and standard therapy groups, but results suggest that there was a survival benefit associated with lanthanum carbonate treatment for patients aged >65 years, who are likely to carry the greatest burden of vascular calcification. These results were similar to those observed in the Dialysis Clinical Outcomes Revisited study, a prospective trial of sevelamer hydrochloride designed to assess survival.

Key words::

• Chronic kidney disease
• Dialysis
• Hyperphosphataemia
• Lanthanum carbonate
• Survival

Transparency

Declaration of funding

This study was funded by Shire Pharmaceuticals, the marketing authorization holder of Fosrenol (lanthanum carbonate). Three of the authors are employees of Shire Pharmaceuticals.

Declaration of financial/other relationships

R.W. acted as a consultant to Shire Pharmaceuticals. R.W. has acted as a consultant to other pharmaceutical/biotechnology companies. None of these are in the area of renal medicine, phosphate-binder therapy or related competitor products. P.Z., M.S. and R.P. are employees of Shire Pharmaceuticals.

Peer reviewers may receive honoraria from CMRO for their review work. Peer Reviewer 1 has disclosed that he/she is a consultant/advisor to Abbot, Amgen, Genzyme, Mitsubishi and Novartis. Peer Reviewer 2 has disclosed that he/she is a recipient of research/grant funding from Amgen, Roche, Affymax and Ortho Biotech; is a consultant/advisor to Amgen, Affymax, Ortho Biotech and Vifor; and is the recipient of honorarium payments from Amgen, Roche, Ortho Biotech and Vifor.

Acknowledgements

Shire Pharmaceuticals provided a grant for Oxford PharmaGenesis™ Ltd to provide medical writing and editorial assistance to the authors.

The data contained in this manuscript have been presented previously. Poster presented at the American Society of Nephrology 41st Annual Meeting, Philadelphia, PA, USA, 4–9 November 2008. Poster presented at the National Kidney Foundation Meeting, Nashville, TN, USA, 25–29 March 2009. Poster presented at the World Congress of Nephrology, Milan, Italy, 22–26 May 2009.

The authors would like to thank the following investigators for their contributions to the SPD405-307 clinical study.

United States: Ahmer H. Qarni, Fargo, ND; Ali Iranmanesh, Salem, VA; Allan Sklar, Binghamton, NY; Allen Lauer, Brockton, MA; Ashraf Selim, Malden, MA; Barry Lankhorst, Sioux Falls, SD; Barry Miskin, West Palm Beach, FL; Beckie Michael, Philadelphia, PA; Bernard Michlin, San Diego, CA; Brian N. Ling, Asheville, NC; Bruce Spinowitz, Flushing, NY; Clyde Pence, Pensacola, FL; Dan Koenig, Raleigh, NC; David Van Wyck, Tucson, AZ; Debesh Mazumdar, New Berlin, WI; Denise Ricker, San Pablo, CA; Donald Sherrard, Seattle, WA; Douglas T. Domoto, St. Louis, MO; Duane G. Wombolt, Norfolk, VA; Earl Dunnigan, Bismark, ND; Edward Frederickson, Conyers, GA; Edward Tokatlian, Phoenix, AZ; Eileen Cook, Austin, TX; Emil Skobeloff, Ridley Park, PA; Fred L. Smardo, Fayetteville, AR; Fredrick Osorio, Ventures Mesa, AZ; Fredrick Rogoff, Greer, SC; George M. Nassar, Houston, TX; Gerald Keightley, Richmond, VA; Ghada Bourjeily, Tiverton, RI; Ghodrat A. Siami, Nashville, TN; Hanna Mawad, Lexington, KY; Harold Locay, Ocala, FL; Hartmut Malluche, Lexington, KY; Howard Hassman, Clementon, NJ; Jacinto Hernandez, Memphis, TN; Jack Moore, Washington, DC; James Kopp, Anderson, SC; James Lee Lewis, Birmingham, AL; James Pederson, Oklahoma City, OK; Jeffrey B. Rosen, Coral Gables, FL; Jesus Navarro, Tampa, FL; Jill Lindberg, New Orleans, LA; John David Anthony, Missoula, MT; John Ervin, Kansas City, MO; John G. Elder, Santa Barbara, CA; John Middleton, Dallas, TX; Jose Cangiano, San Juan, PR; K. Adu Ntoso, Philadelphia, PA; Karl Brinker, Dallas, TX; Keith Kapatkin, Brandon, FL; Kenneth Boren, Mesa, AZ; Kenneth Fisher, Detroit, MI; Kenneth Kleinman, Encino, CA; Lakshmi Natarajan, New Port Ritchey, FL; Laura L. Mulloy, Augusta, GA; Leland Garrett, Raleigh, NC; Leslie Steed, Portland, OR; Lois Anne Katz, New York, NY; M. Edwina Barnett, Torrance, CA; Marc S. Weinberg, Providence, RI; Mark R. Kaplan, Nashville, TN; Martin Topiel, Mount Laurel, NJ; Mary Jo Shaver, Little Rock, AR; Michael Anger, Thornton, CO; Michael Bierle, Little Rock, AR; Michael Germain, West Springfield, MA; Michael Koren, Jacksonville, FL; Michel Chonchol, Denver, CO; Muralidhar Acharya, Newport Richey, FL; N. Martin Lunde, Arden Hills, MN; Phillip Marin, Grand Forks, ND; Pran Kar, Orlando, FL; Rajnish Mehrotra, Torrance, CA; Ramesh Soundararajan, Canfield, OH; Remegio Vilbar, Chicago, IL; Richard Bilinsky, Springfield, IL; Richard Coalson, Beavercreek, OH; Richard Halterman, Boulder, CO; Richard S. Kebler, Bend, OR; Robert A. Moore, Wilmington, NC; Robert Lynn, Bronx, NY; Robert McCrary, Little Rock, AR; Robert Mossey, Great Neck, NY; Robert Tomford, Olympia, WA; Ronald Crock, Canton, OH; Saied Murphy, Atlanta, GA; Sergio Acchiardo, Memphis, TN; Stephen Rifkin, Brandon, FL; Steven G. Rosenblatt, San Antonio, TX; Steven Zeig, Pembroke Pines, FL; Suhail Ahmad, Seattle, WA; Suzanne Swan, Minneapolis, MN; Theodore Herman, Amherst, NY; Thomas C. Marbury, Orando, FL; Thomas Martin, Tacoma, WA; Thomas Rakowski, Arlington, VA; Thomas Tucker, Brunswick, GA; Vaughn W. Folkert, Bronx, NY; Wayne Rodriguez, Melbourne, FL; William B. Smith, New Orleans, LA; William Finn, Chapel Hill, NC; William Klein, Wyomissing, PA; Wolfgang J. Weise, Burlington, VT. South Africa: Alain Assounga, Durban; Charles Swanepoel, Cape Town; Rafik Moosa, Cape Town; Sarala Naicker, Gauteng. Poland: Marian Klinger, Wroclaw, Waldysaw Sulowicz, Cracow.

Notes

*Fosrenol is a registered trademark of Shire Pharmaceuticals, Basingstoke, UK.

†Fosrenol is a registered trademark of Shire Pharmaceuticals, Basingstoke, UK.