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Efficacy, safety and tolerability of tofacitinib in patients with an inadequate response to disease modifying anti-rheumatic drugs: a meta-analysis of randomized double-blind controlled studies.

Berhan A - BMC Musculoskelet Disord (2013)

Bottom Line: The odds of tofacitinib treated patients who met the criteria for an at least a 20% improvement in the American College of Rheumatology scale (ACR 20) was more than 4 times higher than placebo treated patients (overall OR = 4.15; 95% CI, 3.23 to 5.32).Even though the discontinuation rate due to adverse events was not different from placebo groups, tofacitinib was associated with infections (overall SMD = 1.96, 95% CI = 1.428 to 2.676), reduction in neutrophil counts (overall SMD = -0.34, 95% CI = -0.450 to -0.223) and elevated levels of LDL cholesterol and liver enzymes.However, treatment with tofacitinib was associated with infections and laboratory abnormalities.

View Article: PubMed Central - HTML - PubMed

Affiliation: Hawassa University College of Medicine and Health Sciences, P, O, Box: 1560, Hawassa, Ethiopia. asresb@hu.edu.et.

ABSTRACT

Background: This meta-analysis was conducted to determine the efficacy, safety and tolerability of tofacitinib in the treatment of rheumatoid arthritis in patients with an inadequate response or intolerance to at least one of the nonbiologic or biologic disease-modifying antirheumatic drugs (DMARDs).

Methods: Electronic based literature search was conducted in the databases of HINARI (Health InterNetwork Access to Research Initiative), MEDLINE and Cochrane library. The studies included in the meta-analysis were double-blind randomized clinical trials that were conducted in treatment-refractory or intolerant patients with rheumatoid arthritis. The odds ratios (OR), standardized mean differences (SMD) and the 95% confidence intervals (95% CI) were determined by using the random effects model. Heterogeneity among the included studies was evaluated by I² statistics.

Results: The odds of tofacitinib treated patients who met the criteria for an at least a 20% improvement in the American College of Rheumatology scale (ACR 20) was more than 4 times higher than placebo treated patients (overall OR = 4.15; 95% CI, 3.23 to 5.32). Even though the discontinuation rate due to adverse events was not different from placebo groups, tofacitinib was associated with infections (overall SMD = 1.96, 95% CI = 1.428 to 2.676), reduction in neutrophil counts (overall SMD = -0.34, 95% CI = -0.450 to -0.223) and elevated levels of LDL cholesterol and liver enzymes.

Conclusions: Tofacitinib was effective in the treatment of active rheumatoid arthritis in patients with an inadequate response or intolerance to at least one DMARDs. However, treatment with tofacitinib was associated with infections and laboratory abnormalities.

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Related in: MedlinePlus

Flow diagram showing studies selection.
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Figure 1: Flow diagram showing studies selection.

Mentions: Based on the predetermined inclusion criteria, from the retrieved 43 publication, only eight double-blind randomized clinical trials[10-13,16-19] were included in the meta-analysis (Figure 1). Except one study[19] that was conducted in Japan at multiple sites all the included studies recruited patients with rheumatoid arthritis from more than one country. As shown in Table 1, five of the included studies compared the efficacy, safety and tolerability of tofacitinib in combination with background methotrexate against placebo with background methotrexate regimen[10,12,13,18,19]. While the remaining three studies compared tofacitinib monotherapy against placebo[11,16,17]. In all the included studies concomitant medication with stable doses of low-dose corticosteroids (≤10 mg per day prednisone or equivalent), nonsteroidal anti-inflammatory drugs and selective cyclooxygenase-2 inhibitors were allowed for all treatment groups (tofacitinib or placebo groups). From all the selected studies a total of 2,513 patients with rheumatoid arthritis have received one of the four doses of tofacitinib BID with or without methotrexate (3, 5, 10 or 15-mg). While 1,770 patients (controls) have received placebo or placebo with background methotrexate. On the other hand, the risk of bias assessment among the included studies did not demonstrate the presences of biases in randomization, blinding and selective reporting.


Efficacy, safety and tolerability of tofacitinib in patients with an inadequate response to disease modifying anti-rheumatic drugs: a meta-analysis of randomized double-blind controlled studies.

Berhan A - BMC Musculoskelet Disord (2013)

Flow diagram showing studies selection.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4222887&req=5

Figure 1: Flow diagram showing studies selection.
Mentions: Based on the predetermined inclusion criteria, from the retrieved 43 publication, only eight double-blind randomized clinical trials[10-13,16-19] were included in the meta-analysis (Figure 1). Except one study[19] that was conducted in Japan at multiple sites all the included studies recruited patients with rheumatoid arthritis from more than one country. As shown in Table 1, five of the included studies compared the efficacy, safety and tolerability of tofacitinib in combination with background methotrexate against placebo with background methotrexate regimen[10,12,13,18,19]. While the remaining three studies compared tofacitinib monotherapy against placebo[11,16,17]. In all the included studies concomitant medication with stable doses of low-dose corticosteroids (≤10 mg per day prednisone or equivalent), nonsteroidal anti-inflammatory drugs and selective cyclooxygenase-2 inhibitors were allowed for all treatment groups (tofacitinib or placebo groups). From all the selected studies a total of 2,513 patients with rheumatoid arthritis have received one of the four doses of tofacitinib BID with or without methotrexate (3, 5, 10 or 15-mg). While 1,770 patients (controls) have received placebo or placebo with background methotrexate. On the other hand, the risk of bias assessment among the included studies did not demonstrate the presences of biases in randomization, blinding and selective reporting.

Bottom Line: The odds of tofacitinib treated patients who met the criteria for an at least a 20% improvement in the American College of Rheumatology scale (ACR 20) was more than 4 times higher than placebo treated patients (overall OR = 4.15; 95% CI, 3.23 to 5.32).Even though the discontinuation rate due to adverse events was not different from placebo groups, tofacitinib was associated with infections (overall SMD = 1.96, 95% CI = 1.428 to 2.676), reduction in neutrophil counts (overall SMD = -0.34, 95% CI = -0.450 to -0.223) and elevated levels of LDL cholesterol and liver enzymes.However, treatment with tofacitinib was associated with infections and laboratory abnormalities.

View Article: PubMed Central - HTML - PubMed

Affiliation: Hawassa University College of Medicine and Health Sciences, P, O, Box: 1560, Hawassa, Ethiopia. asresb@hu.edu.et.

ABSTRACT

Background: This meta-analysis was conducted to determine the efficacy, safety and tolerability of tofacitinib in the treatment of rheumatoid arthritis in patients with an inadequate response or intolerance to at least one of the nonbiologic or biologic disease-modifying antirheumatic drugs (DMARDs).

Methods: Electronic based literature search was conducted in the databases of HINARI (Health InterNetwork Access to Research Initiative), MEDLINE and Cochrane library. The studies included in the meta-analysis were double-blind randomized clinical trials that were conducted in treatment-refractory or intolerant patients with rheumatoid arthritis. The odds ratios (OR), standardized mean differences (SMD) and the 95% confidence intervals (95% CI) were determined by using the random effects model. Heterogeneity among the included studies was evaluated by I² statistics.

Results: The odds of tofacitinib treated patients who met the criteria for an at least a 20% improvement in the American College of Rheumatology scale (ACR 20) was more than 4 times higher than placebo treated patients (overall OR = 4.15; 95% CI, 3.23 to 5.32). Even though the discontinuation rate due to adverse events was not different from placebo groups, tofacitinib was associated with infections (overall SMD = 1.96, 95% CI = 1.428 to 2.676), reduction in neutrophil counts (overall SMD = -0.34, 95% CI = -0.450 to -0.223) and elevated levels of LDL cholesterol and liver enzymes.

Conclusions: Tofacitinib was effective in the treatment of active rheumatoid arthritis in patients with an inadequate response or intolerance to at least one DMARDs. However, treatment with tofacitinib was associated with infections and laboratory abnormalities.

Show MeSH
Related in: MedlinePlus