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Effect of 3-hydroxy-3-methylglutaryl-coenzyme a reductase inhibitor on disease activity in patients with rheumatoid arthritis: a meta-analysis.

Xing B, Yin YF, Zhao LD, Wang L, Zheng WJ, Chen H, Wu QJ, Tang FL, Zhang FC, Shan G, Zhang X - Medicine (Baltimore) (2015)

Bottom Line: A fixed-effects model was used when there was no significant heterogeneity; otherwise, a random-effects model was used.Statin therapy also significantly reduced tender joint counts, swollen joint counts, ESR, and CRP compared with placebo, but the reduction in HAQ score and VAS was not significant (P > 0.05).This meta-analysis suggested that statin therapy might be effective in the reduction of RA disease activity measured by DAS28, TJC, SJC, as well as ESR and CRP.

View Article: PubMed Central - PubMed

Affiliation: From the Department of Rheumatology and Clinical Immunology (BX, YFY, LDZ, LW, WJZ, HC, QJW, FLT, FCZ, XZ), Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education; and Department of Epidemiology (GS), Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

ABSTRACT
HMG-CoA reductase inhibitors (also known as statins) are widely used as lipid-lowering agents in patients with rheumatoid arthritis (RA) to reduce their cardiovascular risk. However, whether they have an effect on RA disease activity is controversial. This study aimed to investigate the effect of statins on disease activity in RA patients. A systematic literature review was performed using the MEDLINE, EMBASE, Cochrane Library, ISI WEB of Knowledge, Scopus, and Clinical Trials Register databases. Only prospective randomized controlled trials or controlled clinical trials comparing the efficacy of statins with placebo on adult RA patients were included. The efficacy was measured according to the ACR criteria, EULAR criteria, DAS28, HAQ score, ESR, or CRP. The Jadad score was used for quality assessment. The inverse variance method was used to analyze continuous outcomes. A fixed-effects model was used when there was no significant heterogeneity; otherwise, a random-effects model was used. For stability of results, we performed leave-one-study-out sensitivity analysis by omitting individual studies one at a time from the meta-analysis. Publication bias was assessed using Egger test. A total 13 studies involving 737 patients were included in the meta-analysis; 11 studies were included in the meta-analysis based on DAS28, while the other 2 studies were only included in the meta-analysis based on ESR or CRP. The standardized mean difference (SMD) in DAS28 between the statin group and the placebo group was -0.55 (95% CI [-0.83, -0.26], P = 0.0002), with an I2 value of 68%. Subgroup analysis showed that patients with more active disease tended to benefit more from statin therapy (SMD -0.73, P = 0.01) than patients with moderate or low disease activity (SMD -0.38, P = 0.03). Statin therapy also significantly reduced tender joint counts, swollen joint counts, ESR, and CRP compared with placebo, but the reduction in HAQ score and VAS was not significant (P > 0.05). This meta-analysis suggested that statin therapy might be effective in the reduction of RA disease activity measured by DAS28, TJC, SJC, as well as ESR and CRP.

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Subgroup analysis based on type of statin (A) and disease activity (B). A. Atorvastatin produced a greater reduction in DAS28 in RA patients (SMD −0.77, 95% CI [−1.77,−0.36], P = 0.002, I2 = 71%). B. Patients with highly active disease (defined as baseline DAS28 ≥5.1) tended to benefit more from statin therapy compared with patients with moderate and low disease activity (SMD −0.73, 95% CI [−1.28,−0.18], P = 0.01, I2 = 79%). CI = confidence interval, DAS28 =  disease activity score in 28 joints, SMD = standardized mean difference.
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Figure 3: Subgroup analysis based on type of statin (A) and disease activity (B). A. Atorvastatin produced a greater reduction in DAS28 in RA patients (SMD −0.77, 95% CI [−1.77,−0.36], P = 0.002, I2 = 71%). B. Patients with highly active disease (defined as baseline DAS28 ≥5.1) tended to benefit more from statin therapy compared with patients with moderate and low disease activity (SMD −0.73, 95% CI [−1.28,−0.18], P = 0.01, I2 = 79%). CI = confidence interval, DAS28 =  disease activity score in 28 joints, SMD = standardized mean difference.

Mentions: A total of 11 studies used DAS28 to evaluate the effect of statins: 9 presented the DAS28 change from baseline,10–12,16,17,20,23–25 and 2 presented only baseline and final DAS28.18,19 The results are shown in Figure 2. The overall SMD of DAS28 was −0.55 (95% CI [−0.83,−0.26], P = 0.0002), which indicated that the DAS28 reduction in the statin group was 0.55 lower than that in the placebo group. This result was statistically significant. The I2 was 68%, suggesting a high heterogeneity. A subgroup analysis was conducted based on the statin used and the disease activity presented by baseline DAS28 score; the results showed that atorvastatin significantly reduced disease activity measured based on DAS28 (SMD −0.77, 95% CI [−1.17, −0.36], P = 0.0002, I2 = 71%) (shown in Figure 3A). No dose-dependent reduction of disease activity was observed. Furthermore, the patients with higher disease activity (defined as baseline DAS28 ≥5.1) tended to benefit more from statin therapy (SMD −0.73, 95% CI [−1.28, −0.18], P = 0.0007, I2 = 79%) than the patients with moderate and low activity (shown in Figure 3B).


Effect of 3-hydroxy-3-methylglutaryl-coenzyme a reductase inhibitor on disease activity in patients with rheumatoid arthritis: a meta-analysis.

Xing B, Yin YF, Zhao LD, Wang L, Zheng WJ, Chen H, Wu QJ, Tang FL, Zhang FC, Shan G, Zhang X - Medicine (Baltimore) (2015)

Subgroup analysis based on type of statin (A) and disease activity (B). A. Atorvastatin produced a greater reduction in DAS28 in RA patients (SMD −0.77, 95% CI [−1.77,−0.36], P = 0.002, I2 = 71%). B. Patients with highly active disease (defined as baseline DAS28 ≥5.1) tended to benefit more from statin therapy compared with patients with moderate and low disease activity (SMD −0.73, 95% CI [−1.28,−0.18], P = 0.01, I2 = 79%). CI = confidence interval, DAS28 =  disease activity score in 28 joints, SMD = standardized mean difference.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4554148&req=5

Figure 3: Subgroup analysis based on type of statin (A) and disease activity (B). A. Atorvastatin produced a greater reduction in DAS28 in RA patients (SMD −0.77, 95% CI [−1.77,−0.36], P = 0.002, I2 = 71%). B. Patients with highly active disease (defined as baseline DAS28 ≥5.1) tended to benefit more from statin therapy compared with patients with moderate and low disease activity (SMD −0.73, 95% CI [−1.28,−0.18], P = 0.01, I2 = 79%). CI = confidence interval, DAS28 =  disease activity score in 28 joints, SMD = standardized mean difference.
Mentions: A total of 11 studies used DAS28 to evaluate the effect of statins: 9 presented the DAS28 change from baseline,10–12,16,17,20,23–25 and 2 presented only baseline and final DAS28.18,19 The results are shown in Figure 2. The overall SMD of DAS28 was −0.55 (95% CI [−0.83,−0.26], P = 0.0002), which indicated that the DAS28 reduction in the statin group was 0.55 lower than that in the placebo group. This result was statistically significant. The I2 was 68%, suggesting a high heterogeneity. A subgroup analysis was conducted based on the statin used and the disease activity presented by baseline DAS28 score; the results showed that atorvastatin significantly reduced disease activity measured based on DAS28 (SMD −0.77, 95% CI [−1.17, −0.36], P = 0.0002, I2 = 71%) (shown in Figure 3A). No dose-dependent reduction of disease activity was observed. Furthermore, the patients with higher disease activity (defined as baseline DAS28 ≥5.1) tended to benefit more from statin therapy (SMD −0.73, 95% CI [−1.28, −0.18], P = 0.0007, I2 = 79%) than the patients with moderate and low activity (shown in Figure 3B).

Bottom Line: A fixed-effects model was used when there was no significant heterogeneity; otherwise, a random-effects model was used.Statin therapy also significantly reduced tender joint counts, swollen joint counts, ESR, and CRP compared with placebo, but the reduction in HAQ score and VAS was not significant (P > 0.05).This meta-analysis suggested that statin therapy might be effective in the reduction of RA disease activity measured by DAS28, TJC, SJC, as well as ESR and CRP.

View Article: PubMed Central - PubMed

Affiliation: From the Department of Rheumatology and Clinical Immunology (BX, YFY, LDZ, LW, WJZ, HC, QJW, FLT, FCZ, XZ), Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education; and Department of Epidemiology (GS), Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

ABSTRACT
HMG-CoA reductase inhibitors (also known as statins) are widely used as lipid-lowering agents in patients with rheumatoid arthritis (RA) to reduce their cardiovascular risk. However, whether they have an effect on RA disease activity is controversial. This study aimed to investigate the effect of statins on disease activity in RA patients. A systematic literature review was performed using the MEDLINE, EMBASE, Cochrane Library, ISI WEB of Knowledge, Scopus, and Clinical Trials Register databases. Only prospective randomized controlled trials or controlled clinical trials comparing the efficacy of statins with placebo on adult RA patients were included. The efficacy was measured according to the ACR criteria, EULAR criteria, DAS28, HAQ score, ESR, or CRP. The Jadad score was used for quality assessment. The inverse variance method was used to analyze continuous outcomes. A fixed-effects model was used when there was no significant heterogeneity; otherwise, a random-effects model was used. For stability of results, we performed leave-one-study-out sensitivity analysis by omitting individual studies one at a time from the meta-analysis. Publication bias was assessed using Egger test. A total 13 studies involving 737 patients were included in the meta-analysis; 11 studies were included in the meta-analysis based on DAS28, while the other 2 studies were only included in the meta-analysis based on ESR or CRP. The standardized mean difference (SMD) in DAS28 between the statin group and the placebo group was -0.55 (95% CI [-0.83, -0.26], P = 0.0002), with an I2 value of 68%. Subgroup analysis showed that patients with more active disease tended to benefit more from statin therapy (SMD -0.73, P = 0.01) than patients with moderate or low disease activity (SMD -0.38, P = 0.03). Statin therapy also significantly reduced tender joint counts, swollen joint counts, ESR, and CRP compared with placebo, but the reduction in HAQ score and VAS was not significant (P > 0.05). This meta-analysis suggested that statin therapy might be effective in the reduction of RA disease activity measured by DAS28, TJC, SJC, as well as ESR and CRP.

Show MeSH
Related in: MedlinePlus