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*For reference only for medical professionals, it is better to increase the dosage regularly~ Methotrexate (MTX) is a first-line drug for the treatment of rheumatoid arthritis (RA), and it has a wide range of clinical applications
.
When used properly, 30%-40% of patients can achieve low disease activity or clinical remission
.
However, in reality, the response rate of MTX is much worse, which leads many patients to prematurely add other disease-improving anti-rheumatic drugs (DMARDs) including biologics.
In order to avoid cost increase and adverse reactions (AEs), optimization The initial MTX monotherapy is critical
.
Increase the initial dose + rapid increment, can better optimize the MTX monotherapy? One strategy for optimizing MTX is to quickly reach the maximum dose and allow patients to receive this dose for at least 8-12 weeks
.
How can this be achieved? The following methods are worth trying: increase the initial dose of MTX; rapid increase; a combination of the above two
.
The first method is to start the initial dose of MTX from 15 mg instead of the traditional 7.
5 mg.
There is a basis for increasing the initial MTX dose
.
On June 8, 2021, the American College of Rheumatology (ACR) updated the "2021 Rheumatoid Arthritis Treatment Guidelines" recommended starting dose of methotrexate ≥ 15 mg/week
.
The guide further emphasizes the importance of rapidly increasing the dose of MTX
.
However, the efficacy of MTX monotherapy depends largely on the rate of increase of MTX.
Although rapid increase of MTX can provide a faster and better response to the efficacy, it also brings a higher risk of intolerance and AEs, such as cell reduction.
, Pneumonia or elevated transaminase
.
Due to the current lack of head-to-head trials in this field, clinicians are still concerned about the efficacy and safety of rapid increments
.
In order to solve this problem, the study published in Ann Rheum Dis (IF: 16.
102) for the first time, head-to-head compared the starting dose of MTX 15mg/week, "routine" (increased by 5mg every 4 weeks) and "rapid" (every 4 weeks).
2 weeks to increase the efficacy and safety of 5mg) increments
.
What exactly did this study say? Let's take a look~ Research screenshots To solve the dilemma, MTX's first head-to-head research is released! The study included the activity of persons aged 18 to 55 years, disease duration <5 years, no use or no use of MTX (low doses of prednisone and/or hydroxychloroquine, but no other DMARDs).
Tender joints ≥ 4 and swollen joints ≥ 2) 178 patients with RA, all subjects were randomly assigned to the conventional treatment group and the rapid treatment group at a 1:1 ratio.
The starting dose of oral MTX for the two groups was 15 mg/week.
In the treatment group, increase by 5 mg every 4 weeks, and in the rapid treatment group, increase by 5 mg every 2 weeks
.
Until the maximum dose of 25 mg/week is reached, and then continue until 16 weeks
.
The primary end point was the proportion of patients with a good EULAR response at 16 weeks (DAS28-CRP ≤ 3.
2, a decrease of> 1.
2); the secondary end point was the change in DAS28-CRP and the incidence of AEs at 16 weeks
.
▌ Baseline demographic characteristics The majority of patients were female [149 (84%)], the average age was 39.
8 (8.
6) years, the average course of disease was 1.
9 (1.
4) years, and the average DAS28-CRP was 5.
4; when included in the study, only 10% Of patients received low-dose glucocorticoid or hydroxychloroquine treatment
.
All patients were at moderate to high disease activity; most patients (67%) had a disease course of no more than 2 years; only 13 patients had received the best dose of methotrexate for a short period of time (3-6 months) ( 7.
5-15 mg) treatment
.
▌ There was no significant difference in the efficacy of the two groups of patients at 16 weeks.
At 8 weeks and 16 weeks, there was no significant difference in the proportion of patients who achieved a good EULAR response in the rapid and conventional increment groups
.
At 8 weeks and 16 weeks, there was no significant difference between the two groups in the proportion of patients with good/moderate EULAR response; at 8 weeks and 16 weeks, there was no difference in the proportion of patients in the two groups that achieved remission, low disease activity, and ΔDAS28-CRP>1.
2 Significant difference (all p>0.
05) (Table 1)
.
Table 1 Comparison of the efficacy and response of the two groups of patients treated for 8 weeks and 16 weeks.
Since there is no difference in efficacy between the two groups, what about the safety? ▌ Short-term gastrointestinal adverse events increased in the rapid increment group As can be seen from Figure 1 (A), at 8 weeks, the incidence of gastrointestinal adverse reactions in the rapid increment group was significantly higher than that in the conventional group, and the difference was statistically significant (P=0.
048), however, this difference disappeared at 16 weeks (p=0.
14)
.
There were no serious adverse reactions such as pneumonia, severe infection, or death in this study
.
There was no significant difference between the two groups of patients in the side effects such as leukopenia, thrombocytopenia, elevated transaminase, and hair loss
.
Figure 1 The main symptoms and laboratory adverse reactions in the routine and rapid methotrexate increment groups at 8 weeks (A) and 16 weeks (B) Note: GI: gastrointestinal adverse reactions; WBC: white blood cell count summary: this The results of this study show that when the initial dose of MTX is 15 mg/week, the effect of increasing 5 mg every 2 weeks is not better than increasing 5 mg every 4 weeks, but the rapid increase in the first 8 weeks did lead to an increase in gastrointestinal disorders , The difference in safety is still a wake-up call for us
.
So faster is not always better
.
All in all, MTX is still the gold standard drug for the treatment of RA worldwide, and optimizing its drug delivery strategy can provide better guidance for clinicians
.
References: Jain S, Dhir V, et al.
Comparison of two dose escalation strategies of methotrexate in active rheumatoid arthritis: a multicentre,parallel group,randomised controlled trial[J].
Ann Rheum Dis.
2021 Jun 10:annrheumdis-2021- 220512.
.
When used properly, 30%-40% of patients can achieve low disease activity or clinical remission
.
However, in reality, the response rate of MTX is much worse, which leads many patients to prematurely add other disease-improving anti-rheumatic drugs (DMARDs) including biologics.
In order to avoid cost increase and adverse reactions (AEs), optimization The initial MTX monotherapy is critical
.
Increase the initial dose + rapid increment, can better optimize the MTX monotherapy? One strategy for optimizing MTX is to quickly reach the maximum dose and allow patients to receive this dose for at least 8-12 weeks
.
How can this be achieved? The following methods are worth trying: increase the initial dose of MTX; rapid increase; a combination of the above two
.
The first method is to start the initial dose of MTX from 15 mg instead of the traditional 7.
5 mg.
There is a basis for increasing the initial MTX dose
.
On June 8, 2021, the American College of Rheumatology (ACR) updated the "2021 Rheumatoid Arthritis Treatment Guidelines" recommended starting dose of methotrexate ≥ 15 mg/week
.
The guide further emphasizes the importance of rapidly increasing the dose of MTX
.
However, the efficacy of MTX monotherapy depends largely on the rate of increase of MTX.
Although rapid increase of MTX can provide a faster and better response to the efficacy, it also brings a higher risk of intolerance and AEs, such as cell reduction.
, Pneumonia or elevated transaminase
.
Due to the current lack of head-to-head trials in this field, clinicians are still concerned about the efficacy and safety of rapid increments
.
In order to solve this problem, the study published in Ann Rheum Dis (IF: 16.
102) for the first time, head-to-head compared the starting dose of MTX 15mg/week, "routine" (increased by 5mg every 4 weeks) and "rapid" (every 4 weeks).
2 weeks to increase the efficacy and safety of 5mg) increments
.
What exactly did this study say? Let's take a look~ Research screenshots To solve the dilemma, MTX's first head-to-head research is released! The study included the activity of persons aged 18 to 55 years, disease duration <5 years, no use or no use of MTX (low doses of prednisone and/or hydroxychloroquine, but no other DMARDs).
Tender joints ≥ 4 and swollen joints ≥ 2) 178 patients with RA, all subjects were randomly assigned to the conventional treatment group and the rapid treatment group at a 1:1 ratio.
The starting dose of oral MTX for the two groups was 15 mg/week.
In the treatment group, increase by 5 mg every 4 weeks, and in the rapid treatment group, increase by 5 mg every 2 weeks
.
Until the maximum dose of 25 mg/week is reached, and then continue until 16 weeks
.
The primary end point was the proportion of patients with a good EULAR response at 16 weeks (DAS28-CRP ≤ 3.
2, a decrease of> 1.
2); the secondary end point was the change in DAS28-CRP and the incidence of AEs at 16 weeks
.
▌ Baseline demographic characteristics The majority of patients were female [149 (84%)], the average age was 39.
8 (8.
6) years, the average course of disease was 1.
9 (1.
4) years, and the average DAS28-CRP was 5.
4; when included in the study, only 10% Of patients received low-dose glucocorticoid or hydroxychloroquine treatment
.
All patients were at moderate to high disease activity; most patients (67%) had a disease course of no more than 2 years; only 13 patients had received the best dose of methotrexate for a short period of time (3-6 months) ( 7.
5-15 mg) treatment
.
▌ There was no significant difference in the efficacy of the two groups of patients at 16 weeks.
At 8 weeks and 16 weeks, there was no significant difference in the proportion of patients who achieved a good EULAR response in the rapid and conventional increment groups
.
At 8 weeks and 16 weeks, there was no significant difference between the two groups in the proportion of patients with good/moderate EULAR response; at 8 weeks and 16 weeks, there was no difference in the proportion of patients in the two groups that achieved remission, low disease activity, and ΔDAS28-CRP>1.
2 Significant difference (all p>0.
05) (Table 1)
.
Table 1 Comparison of the efficacy and response of the two groups of patients treated for 8 weeks and 16 weeks.
Since there is no difference in efficacy between the two groups, what about the safety? ▌ Short-term gastrointestinal adverse events increased in the rapid increment group As can be seen from Figure 1 (A), at 8 weeks, the incidence of gastrointestinal adverse reactions in the rapid increment group was significantly higher than that in the conventional group, and the difference was statistically significant (P=0.
048), however, this difference disappeared at 16 weeks (p=0.
14)
.
There were no serious adverse reactions such as pneumonia, severe infection, or death in this study
.
There was no significant difference between the two groups of patients in the side effects such as leukopenia, thrombocytopenia, elevated transaminase, and hair loss
.
Figure 1 The main symptoms and laboratory adverse reactions in the routine and rapid methotrexate increment groups at 8 weeks (A) and 16 weeks (B) Note: GI: gastrointestinal adverse reactions; WBC: white blood cell count summary: this The results of this study show that when the initial dose of MTX is 15 mg/week, the effect of increasing 5 mg every 2 weeks is not better than increasing 5 mg every 4 weeks, but the rapid increase in the first 8 weeks did lead to an increase in gastrointestinal disorders , The difference in safety is still a wake-up call for us
.
So faster is not always better
.
All in all, MTX is still the gold standard drug for the treatment of RA worldwide, and optimizing its drug delivery strategy can provide better guidance for clinicians
.
References: Jain S, Dhir V, et al.
Comparison of two dose escalation strategies of methotrexate in active rheumatoid arthritis: a multicentre,parallel group,randomised controlled trial[J].
Ann Rheum Dis.
2021 Jun 10:annrheumdis-2021- 220512.
