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EULAR'S NEWLY RELEASED GUIDE, LET'S GET A SNEAK PEEK!
Get a sneak peek of the recent European Union Against Rheumatism (EULAR) on the use of rheumatoid arthritis (RA) with disease-modifying antirheumatic drugs (DMARDs
).
Figure: The Recommendation Screenshot
Working Group assigned the level of evidence and the strength of the recommendations based on three systematic literature on the safety and efficacy of DMARDs and glucocorticoids (GCs) from 2019
.
Conventional synthetic DMARDs [methotrexate (MTX), leflunomide, sulfasalazine], hormones, biologics DMARDs [tumor necrosis factor inhibitors (adalimumab, setuzumab, etanercept, golimumab, infliximab, including biosimilars), abatacept, rituximab, tocilizumab, salivizumab], There are 5 general principles and 11 recommendations
on the safety, efficacy and cost of targeted synthesis of DMARDs (JAK inhibitors tofacitinib, baricitinib, fegotinib, upatinib).
Before formally introducing the content of the guide, let's take a look at the following common terms
.
Adverse prognostic factors: ► Sustained moderate or high disease activity (after CSDMARD treatment) ► High acute phase reactant levels ► High number of swollen joints ► RF and/or ACCA positive, especially high levels ► Early bone erosion present ► Failure
of 2 or more csDMARDs Low-dose glucocorticoids: ≤7.
5 mg/day prednisone dose
short course: up to 3 months
drug reduction: ► Reduction of drug dose or increase between doses► Definition of remission that may include discontinuation but only after slow tapering
:
ACR-EULAR Definition of Remission Sustained remission: ACR-EULAR defines remission ≥ low disease activity for 6 months
: Sustained low disease activity in a state of low disease activity as assessed by disease activity including joint count:
Low disease activity ≥ moderate to high disease activity at 6 months
:
DMARDs are synthesized from moderate to high disease activity status measured by disease activity
, including joint count
►Conventional synthesis of DMARDs such as methotrexate, leflunomide, sulfasalazine, hydroxychloroquine ► Targeted synthesis of DMARDs such as baricitinib, figuotinib, tofacitinib and upatinib
biologics DMARDs
►Biogenic DMARDs
TNFi: adalimumab, cetolizumab, etanercept, golimumab, infliximab IL-6Ri: salivizumab, tocilizumab B cells (CD20): rituximab
►Biomimic DMARDs
, adalimumab, etanercept, infliximab, rituximab and other imitations
Table 1: Definitions of commonly used terms
5 General Principles 1.
Treatment of patients with RA should aim for the best treatment and must be based on a shared decision
between the patient and the rheumatologist
2.
Treatment depends on disease activity, safety concerns, and other factors, such as comorbidities and the progression of
organ tissue damage.
3.
Rheumatologists mainly take care of RA patients
.
4.
Patients need multiple drugs with different modes of action to solve the heterogeneity of RA; They may need multiple consecutive treatments
throughout their lives.
Comments: This principle was first proposed in 2019 and widely recognized
by the industry in 2022.
It has been suggested that drug regimens should not be changed too frequently, as all drugs can take weeks or months to produce an effect, so the efficacy
of each new therapy should not be judged too early.
.
Therefore, drug exchange
should be avoided before and in the case of occasional and transient disease recurrence, unless due to drug safety concerns.
5.
Having RA can lead to high personal, medical and social costs, which should be considered
in the treatment and management of rheumatologists.
11 management recommendations 1.
DMARD therapy should be started immediately as soon as RA is diagnosed (recommended intensity: 1a; Evidence level: A).
Comments: This recommendation emphasizes the importance of early diagnosis and treatment of RA to avoid poor prognosis or even disability caused by long-term delay in treatment, as well as serious complications
of other important organ function impairment.
2.
Treatment should aim to achieve the goal of sustained remission or low disease activity in each patient (recommended intensity: 1a; Evidence level: A).
Comments: Emphasizing the importance of standard treatment for RA patients, studies have shown that long-term unqualified RA treatment still has a continuous progression and increased likelihood of disease recurrence, and there is no significant benefit
in the long run.
3.
Frequent surveillance of disease activity (every 1-3 months); If there is no improvement up to 3 months after initiation of treatment or 6 months does not meet the target, the treatment regimen should be adjusted (recommended intensity: 2 b; Evidence level: B).
Comments: This recommendation is recognized by rheumatologists worldwide; It is particularly important
in patient follow-up, monitoring disease activity, assessing for adverse drug reactions, and vital organ damage.
4.
MTX should be the first choice for treatment (recommended strength: 1a; Evidence level: A).
Comments: It is reiterated that MTX as the cornerstone or anchoring role of RA treatment, compared with other drugs, MTX as the core position in RA treatment is irreplaceable
in terms of efficacy, safety, convenience, and economic efficacy.
5.
For patients with contraindications to MTX (or early intolerance), leflunomide or sulfasalazine should be considered as part of the (first) treatment option (recommended intensity: 1a; Evidence level: A).
Comments: Domestic rheumatologists may choose elamod or leflunomide more for patients with contraindications to MTX, while sulfasalazine is more commonly used when peripheral joints of spondyloarthritis (SpA) are involved, which is worth further discussion
.
6.
The use of short-term GCs should be considered when starting treatment with csDMARDs or changing different dosage regimens and routes of administration, but reducing and discontinuing the dose as soon as clinically feasible (recommended intensity: 1a; Evidence level: A).
Comments: Compared to the 2019 version of the recommendation, the 2022 version of the recommendation added "discontinuation of the drug", 90% of patients in all tapering and discontinuation regimens did stop GCs, and only about 10% of patients were still using GCs
after 24 months.
Meanwhile, a partially published meta-analysis reported GC in approximately 10% of patients
within 6-12 months after the bridging regimen ended.
However, these data come from clinical trials
.
In reality, around half of patients are treated with chronic GCs, so the updated recommendations call more strongly than ever to stop using GCs
as soon as possible.
7.
If the first csDMARDs do not meet the therapeutic goal, other csDMARDs should be considered in the absence of adverse prognostic factors (recommended strength: 5; Evidence level: D).
8.
If the first csDMARDs do not meet the therapeutic goal, bDMARDs should be added when there are adverse prognostic factors, JAK inhibitors can be considered, but the relevant risk factors must be considered (recommended intensity: efficacy 1a; Security 1b; Certainty of evidence: efficacy A; Security B).
Comments: JAK inhibitors have been widely used as oral targeted drugs for the treatment of RA in recent years, but risk factors for related cardiovascular events and malignancy must be considered when prescribing, and rheumatologists agree that this recommendation is agreed
.
9.
IL-6 inhibitors and tsDMARDs may have some advantages over other bDMARDs in patients who cannot use cSDARDs (recommended strength: 1a; Evidence level: A).
10.
If treatment fails with bDMARDs or tsDMARDs, treatment with another bDMARDs and tsDMARDs should be considered; If treatment with one TNF or IL-6 receptor inhibitor fails, the patient can switch to another mode of action or a second TNF/IL-6R inhibitor (recommended intensity: 1a/1b; Evidence level: A/+D).
11.
After discontinuation of GCs and sustained remission in patients, consideration can be given to reducing the dose of DMARDs (bDMADs/tsDMARDs and/or csDMARDs) (recommended intensity: 1b; Evidence level: A).
TABLE 2: EULAR RA MANAGEMENT RECOMMENDATIONS
**Special emphasis: risk factors for the following cardiovascular events and malignancy must be considered when prescribing JAK inhibitors: age over 65 years, current or past smoking, other cardiovascular risk factors (eg, diabetes, obesity, hypertension), other risk factors for malignancy (current or past malignancy other than successfully treated non-melanoma skin cancer), risk factors for thromboembolic events (myocardial infarction or heart failure, cancer, hereditary coagulopathy, or history of thrombosis), and patients taking hormonal contraceptives or hormone replacement therapy, undergoing major surgery, or prolonged bed rest).Summary
proposal is the fewest ever.
Compared to the previous version, no new drug classes
have emerged.
At the same time, all overarching principles and 6 of the 11 recommendations remained unchanged, attesting to the validity and maturity of
these previous recommendations.
This recommendation is described in detail from general principles to specific management recommendations; From the perspective of drug efficacy, safety, economic cost, long-term practice management, doctor-patient joint decision-making, long-term disease monitoring and evaluation time, the core position of methotrexate in RA treatment, scientific and standardized use of hormones, and biologics selection recommendations, some precautions for the use of JAK are specially proposed for clinicians' reference
.
References: 1.
Smolen JS, et al.
EULAR recommendations for the management ofrheumatoid arthritis with synthetic and biological disease-modification antirheumatic drugs: 2022 update.
Ann Rheum Dis 2022;0:1–16.
doi:10.
1136/ard-2022-223356.
Where to see more rheumatology clinical knowledge? Come to the "doctor's station" and take a look 👇
