Session Information
Session Type: Abstract Submissions (ACR)
Background/Purpose: Data from randomized clinical trials (RCTs) and their open-label extensions in patients (pts) with rheumatoid arthritis (RA) indicate that tocilizumab (TCZ) may be associated with treatment-related decreases in neutrophils and platelets and increases in lipids and liver enzymes1; however, analyses of treatment effects on laboratory parameters in real-world pt populations are limited. The objective of this study was to assess changes in laboratory measures with TCZ treatment over 6 months in pts with RA from the prospective CORRONA CERTAIN substudy.
Methods: Pts with at least moderate disease activity (CDAI >10) initiating TCZ were eligible for the ongoing biologic agent comparative effectiveness study (CERTAIN) nested within CORRONA. The decision to start TCZ was made by the physician prior to enrollment. Efficacy outcomes (CDAI and HAQ) and laboratory measures (CRP, hemoglobin, cell counts, lipids and liver enzymes) were assessed at baseline (BL) and every 3 months for a year. Cutoff values for laboratory normals were based on US Prescribing Information, where applicable.2 Data for pts who have completed a 6-month visit are presented.
Results: Of 1620 pts with RA enrolled in CERTAIN, 244 pts initiated TCZ therapy between November 2010, and February 2013. At the time of analysis, 65 pts had not yet completed 6 months of follow-up and 43 pts had exited the CERTAIN study prior to 6 months; available reasons for TCZ discontinuation include 8 safety (1 serious side effect), 11 efficacy and 4 other reasons. Of the 136 pts who completed a 6-month follow-up visit, 109 (80.1%) were female, 120 (88.2%) were Caucasian and 72/128 (56.3%) were seropositive at BL; the mean ± SD age and RA duration were 57.9 ± 12.9 years and 11.9 ± 9.4 years, respectively. A total of 41 (30.1%) pts received TCZ as monotherapy; of the pts initiating TCZ in combination with nonbiologic DMARDs, 72 (75.8%) received concurrent MTX. After 6 months of TCZ treatment, median (IQR) CDAI improved from 31.0 (23.0-41.7) to 15.0 (8.0-26.3). Median (IQR) HAQ improved from 1.25 (0.5-1.75) to 1.00 (0.5-1.63). Changes in laboratory values of interest over 6 months are shown in Table 1. The proportion of pts with anemia decreased from 19.5% at BL to 11.0% and 1.7% of pts developed neutropenia at 6 months. Median lipid values increased at 6 months and 15.5% and 17.9% of pts respectively had AST and ALT above the upper limit of normal at 6 months vs 2.7% and 6.5% at BL.
Conclusion: TCZ improved clinical outcomes and was associated with alteration of specific laboratory parameters in pts with RA. The interim analyses of laboratory changes are similar with observations from RCTs for 6 months. Continued enrollments and longer follow-up in CERTAIN are needed to further assess clinical relevance of these laboratory changes.
1. Genovese MC, et al. J Rheumatol. 2013;40:768-80; 2. Actemra REMS. http://www.fda.gov. Accessed June 2013.
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Table 1. Laboratory Measures for Patients Initiating TCZ Therapy Within CERTAIN at Baseline and After 6 Months Follow-up
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Laboratory Measurements
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Baseline
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6-Month Follow-up
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CRP, median (IQR), n=120 |
3.88 (1.64-12.50) |
0.57 (0.23-1.42) |
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Hemoglobin (g/dL), median (IQR), n=118 Anemia, n (%)a |
13.1 (12.1-14.0) 23 (19.5) |
13.4 (12.4-14.2) 13 (11.0) |
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Neutrophils (/µL), median (IQR), n=118 <500, n (%) 500 to 1000, n (%) >1000, n (%) Neutropenia (%)b |
4490 (3280-6310) 0 (0.0) 0 (0.0) 118 (100.0) 0 (0.0) |
3785 (2310-5430) 0 (0.0) 2 (1.7) 116 (98.3) 2 (1.7) |
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Platelets (/µL x1000), median (IQR), n=115 <50,000, n (%) 50,000 to 100,000, n (%) >100,000, n (%) Thrombocytopenia (%)c |
278 (232-328) 0 (0.0) 0 (0.0) 115 (100.0) 0 (0.0) |
227 (192-284) 0 (0.0) 0 (0.0) 115 (100.0) 0 (0.0) |
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TC (mg/dL), median (IQR), n=123 <200, n (%) ≥200, n (%) |
195.0 (171.0-221.0) 69 (56.1) 54 (43.9) |
210.0 (184.0-240.0) 52 (42.3) 71 (57.7) |
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HDL (mg/dL), median (IQR), n=123 <40, n (%) ≥40, n (%) |
60 (49.0-73.0) 13 (10.6) 110 (89.4) |
61.0 (48.0-71.0) 12 (9.8) 111 (90.2) |
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LDL (mg/dL), median (IQR), n=122 <100, n (%) ≥100, n (%) |
114.5 (94.0-132.0) 36 (29.5) 86 (70.5) |
124.5 (101.0-151.0) 29 (23.8) 93 (76.2) |
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TG (mg/dL), median (IQR), n=123 <150, n (%) ≥150, n (%) |
138.0 (94.0-190.0) 71 (57.7) 52 (42.3) |
152.0 (106.0-232.0) 61 (49.6) 62 (50.4) |
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AST (U/L), median (IQR), n=110 Normal (ULN), n (%) >1 to 3x ULN, n (%) >3 to 5x ULN, n (%) >5x ULN, n (%) |
21.0 (17.0-26.0) 107 (97.3) 3 (2.7) 0 (0.0) 0 (0.0) |
24.0 (20.0-31.0) 93 (84.6) 17 (15.5) 0 (0.0) 0 (0.0) |
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ALT (U/L), median (IQR), n=123 Normal (ULN), n (%) >1 to 3x ULN, n (%) >3 to 5x ULN, n (%) >5x ULN, n (%) |
21.0 (16.0-29.0) 115 (93.5) 8 (6.5) 0 (0.0) 0 (0.0) |
26.0 (20.0-42.0) 101 (82.1) 20 (16.3) 2 (1.6) 0 (0.0) |
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aAnemia defined as <11.5 g/dL for females, <13.2 g/dL for males. bNeutropenia defined as <1000 neutrophils/µL. cThrombocytopenia defined as <50,000 platelets/µL. ALT, alanine aminotransferase; AST, aspartate aminotransferase; CDAI, clinical disease activity index; CRP, C-reactive protein; HAQ, health assessment questionnaire; HDL, high-density lipoprotein; LDL, low-density lipoprotein; TC, total cholesterol; TCZ, tocilizumab; TG, triglycerides; ULN, upper limit of normal; WBC, white blood cells.
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Disclosure:
D. A. Pappas,
CORRONA Inc,
3,
Novartis Pharmaceutical Corporation,
5,
Columbia University,
6;
A. John,
Genentech, Inc.,
3;
J. M. Kremer,
CORRONA ,
1,
CORRONA ,
3;
C. Karki,
Corrona, Inc.,
3;
T. Sommers,
CORRONA ,
3;
G. W. Reed,
Corrona, Inc,
3;
J. R. Curtis,
Roche/Genentech, UCB, janssen, CORRONA, Amgen, Pfizer, BMS, Crescendo, AbbVie,
2,
Roche/Genentech, UCB, janssen, CORRONA, Amgen, Pfizer, BMS, Crescendo, AbbVie,
5;
A. Shewade,
Genentech, Inc.,
3;
J. D. Greenberg,
Corrona Inc.,
1,
Corrona, Inc,
5,
AstraZeneca,
5,
Novartis Pharmaceutical Corporation,
5,
Pfizer Inc,
5.
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