The Association Between Hydroxyurea Treatment and Pain Intensity, Analgesic Use, and Utilization in Ambulatory Sickle Cell Anemia Patients


  • 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

Wally R. Smith, MD, Division of Quality Health Care, Virginia Commonwealth University, Box 980306, Richmond, VA 23060, USA. Tel: 804-828-6938; Fax: 804-828-4862; E-mail:


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.