Investigators of the Multicenter Study of Hydroxyurea in Sickle Cell Anemia (randomized controlled trial).
The Association Between Hydroxyurea Treatment and Pain Intensity, Analgesic Use, and Utilization in Ambulatory Sickle Cell Anemia Patients
Version of Record online: 11 APR 2011
Wiley Periodicals, Inc.
Volume 12, Issue 5, pages 697–705, May 2011
How to Cite
Smith, W. R., Ballas, S. K., McCarthy, W. F., Bauserman, R. L., Swerdlow, P. S., Steinberg, M. H., Waclawiw, M. A. and the Investigators of the Multicenter Study of Hydroxyurea in Sickle Cell Anemia (2011), The Association Between Hydroxyurea Treatment and Pain Intensity, Analgesic Use, and Utilization in Ambulatory Sickle Cell Anemia Patients. Pain Medicine, 12: 697–705. doi: 10.1111/j.1526-4637.2011.01096.x
Clinical Centers: University of North Carolina, Chapel Hill, NC: E Orringer, S Jones, D Strayhorn Duke University, Durham, NC: W Rosse, G Phillips, D Peace, A Johnson-Telfair Medical College of Georgia, Augusta, GA: P Milner, A Kutlar, A Tracy Thomas Jefferson University, Philadelphia, PA: SK Ballas, GE Allen, J Moshang, B Scott University of Mississippi, Jackson, MS: M Steinberg, A Anderson, V Sabahi University of Miami, Miami, FL: C Pegelow, D Temple, E Case, R Harrell, S Childerie San Francisco General Hospital, San Francisco, CA: S Embury, B Schmidt, D Davies University of Illinois, Chicago, IL: M Koshy, N Talischy-Zahed, L Dorn, G Pendarvis, M McGee Michael Reese Hospital, Chicago, IL: M Telfer, A Davis Howard University, Washington, DC: O Castro, H Finke, E Perlin, J Siteman University of Medicine and Dentistry of New Jersey, Newark, NJ: P Gascon, P di Paolo, S Gargiulo Emory University, Atlanta, GA: J Eckman, JH Bailey, A Platt, L Waller St. Luke's—Roosevelt Medical Center, New York, NY: G Ramirez, V Knors, S Hernandez, EM Rodriguez, E Wilkes Children's Hospital of Oakland, Oakland, CA: E Vichinsky, S Claster, A Earles, K Kleman, K McLaughlin Virginia Commonwealth University, Richmond, VA: P Swerdlow, W Smith, B Maddox, L Usry, A Brenner, K Williams, R O'Brien, K Genther Case Western Reserve University, Cleveland, OH: S Shurin, B Berman, K Chiarucci, L Keverline Hospital for Sick Children, Toronto, Ontario: N Olivieri, D Shaw, N Lewis Brigham and Women's Hospital, Boston, MA: K Bridges, B Tynan, C Winograd Interfaith Medical Center, Brooklyn, NY: R Bellevue, H Dosik, M Sheikhai, P Ryans, H Souffrant University of Alabama, Birmingham, AL: J Prchal, J Braddock, T McArdle University of Pittsburgh, Pittsburgh, PA: T Carlos, A Schmotzer, D Gardner
Central Office Staff: Johns Hopkins University, Baltimore, MD: S Charache, R Moore, G Dover, M Bergner, C Ewart, S Eckert, C Lent, J Ullrich, L Fishpaw, G Tirado, J Gibson, T Moeller, T Nagel
Data Coordinating Center: Maryland Medical Research Institute, Baltimore, MD: M Terrin, FB Barton, RP McMahon, C Handy, D Harris, M Canner, J Depkin, N Meinert, M Carroll, R Giro, S Karabelas, C Kelly
Crisis Review Committee: M Heyman, P Beilinson, M Druskin, P Ellis, WA Flood, S Kravitz, S Lanzkron, V Lorica, A Moliterno, A Nahum, JA Nesbitt III, L Rosenthal, W Sharfman, M Streiff, M Wachsman, P Bray, C Van Dang, J Casella, M McGuire, L Patrick, H Schaad, C Steiner
Data and Safety Monitoring Board: C Johnson, A Bank, G Cutter, CE Davis, O Huntley, L Lessin, O Platt, M Gray-Secundy
Project Office: National Heart, Lung, and Blood Institute, Bethesda, MD: D Bonds, C Reid, N Geller, M Waclawiw
- Issue online: 12 MAY 2011
- Version of Record online: 11 APR 2011
- Chronic Pain;
- Pain Management;
- Outcome Assessment;
- Randomized Controlled Trial
Background. We compared daily pain, home analgesic use, and utilization among ambulatory adults in the randomized Multicenter Study of Hydroxyurea in Sickle Cell Anemia (MSH). We related the fetal hemoglobin (HbF) hydroxyurea response to these response variables.
Methods. Patients rated their sickle cell pain intensity (0–9), use of analgesics, and visits for pain daily. Diaries were collected biweekly, and intensity was collapsed into single interval ratings. The interval proportions of days of analgesic use and medical visits for pain were also calculated. Group comparisons were made by intention to treat as well as by HbF change levels from baseline to 2 years of treatment (placebo and low, medium, high, or very high response).
Results. A total of 134 (44.8%) enrollees completed 2 years of follow-up. Pain intensity correlated with analgesic use (r = 0.83, P > 0.0001) and utilization (r = 0.50, P < 0.0001). Pain intensity was lower for patients on hydroxyurea (2.51 ± 0.062 vs 2.82 ± 0.063 placebo, F(1,270) = 11.65, P = 0.0007). The difference, though small, appeared early and was sustained. Analgesic use and utilization were also slightly lower (analgesic use: F(1,270) = 11.97, P = 0.0006; utilization: F(1,270) = 32.0, P < 0.0001). Each was statistically significantly lower among hydroxyurea patients with higher HbF treatment responses to hydroxyurea.
Conclusions. Hydroxyurea usage led to a small, statistically significant reduction in daily pain, analgesic use, and utilization in adults in MSH, corroborating previously shown larger reductions in crises and mortality. The degree of daily symptomatic reduction was related to the size of the HbF treatment response, further confirming HbF response as a useful laboratory correlate.