Risk of higher dose methotrexate for renal impairment in patients with rheumatoid arthritis

Vanni

et al. 2021

JASN

Background: Low-dose methotrexate (LD-MTX) is contraindicated in advanced chronic kidney disease (CKD), but the kidney safety in normal kidney function or mild-to-moderate CKD is less clear. Methods: We performed a secondary analysis for eGFR and kidney AEs using the randomized double-blind, placebo-controlled Cardiovascular Inflammation Reduction Trial. Adults with cardiovascular disease and diabetes and/or metabolic syndrome were randomly allocated to oral LD-MTX (target dose 15-20 mg/week) or placebo. All participants took folic acid 1 mg six days/week. Exclusion criteria included systemic rheumatic disease and creatinine clearance <40 mL/min. The least-squares mean ΔeGFR from baseline was calculated at each study visit; the difference in eGFR between LD-MTX and placebo was compared. We used Cox proportional hazards models to compare rates of kidney AEs for LD-MTX versus placebo. Results: A total of 2,391 participants were randomized to LD-MTX and 2,395 to placebo. At baseline, mean age was 66 years, 19% were female, and mean eGFR was 80.0mL/min/1.73m2 (54% had Stage 2 CKD and 18% had Stage 3 CKD). Median follow-up was 23 months. The LD-MTX group had less decline in eGFR than placebo (difference in least-squares mean ΔeGFR from baseline to on-treatment visits: 0.93mL/min/1.73m2, 95%CI 0.45-1.40, p<0.001). There were 138 (incidence rate [IR] 2.97 per 100 person-years) kidney AEs in the LD-MTX group and 184 (IR 3.99 per 100 person-years) among placebo (hazard ratio [HR] 0.73, 95%CI 0.59-0.91) during safety laboratory monitoring. Conclusions: These results demonstrate the kidney safety of LD-MTX among patients with normal kidney function or mild/moderate CKD at baseline.

Section: Discussionmentioning

confidence: 99%

Effect of Low-Dose Methotrexate on eGFR and Kidney Adverse Events: A Randomized Clinical Trial

Vanni

et al. 2021

JASN

“…Methotrexate in high doses can cause renal toxicity, and recommendations for using low-moderate dose methotrexate depend on glomerular filtration rate (GFR) [ 70 ]. Doses > 12 mg/week were associated with a decrease in GFR of 0.25 over 1 year compared to 8–12 mg/week [ 71 ]. In an older study of 21 patients who received methotrexate 7.5 mg/week for 2 years, there was an 11% reduction in creatinine clearance after 6 months with reduction in clearance of methotrexate by 25% [ 72 ].…”

Section: Associated Co-morbiditiesmentioning

confidence: 99%

Psoriatic Arthritis: The Influence of Co-morbidities on Drug Choice

Patel

Kumthekar

2021

Rheumatol Ther

Psoriatic arthritis (PsA) is associated with a higher burden of co-morbidities such as obesity, cardiovascular disease, non-alcoholic fatty liver disease, inflammatory eye disease, inflammatory bowel disease, skin cancer and depression compared to the general population. In the last 20 years, the therapeutic options for PsA have increased exponentially with the availability of tumor necrosis factor-alpha (TNF) inhibitors, interleukin (IL)-17 inhibitors, IL-12/23 inhibitors and Janus kinases/signal transducer and activator of transcription proteins (JAK/STAT) inhibitors. The articular and extra-articular manifestations of PsA usually dictate the treatment choice but important consideration must be given to the corresponding co-morbidities while deciding the drug therapy due to associated safety profile, effect on disease activity, etc. This review provides a comprehensive review of common co-morbidities in PsA and how they can influence treatment choices.

“…As an anti-rheumatic drug, methotrexate is widely used in clinics (33). Studies have found that it has a certain regulatory effect on the apoptosis factors Bcl-2 and caspase 3 and the inflammatory factor TNF-α (34)(35)(36).…”

Section: Discussionmentioning

confidence: 99%

The method of Yiqi Yangyin Tongluo can attenuate the pyroptosis of rheumatoid arthritis chondrocytes through the ASIC1a/NLRP3 signaling pathway

Zhao¹,

Chen²,

Zhi-min³

et al. 2022

Ann Transl Med

Background: Based on the ASIC1a/NLRP3 signaling pathway, we explored the specific molecular mechanism of the pyroptosis of rheumatoid arthritis (RA) chondrocytes by the method of nourishing qi, nourishing yin, and dredging collaterals to provide new ideas for the treatment of this disease.Methods: A total of 50 rats were divided into a normal group, model group, methotrexate group, Yiqi Yangyin Tongluo group, and combined group. Except for the normal control group, the other groups used Freund's complete adjuvant (FCA) to make RA rat model. The arthritis index and ankle joint swelling of rats in each group were recorded. HE staining and ELISA were used to assess the pathology of the ankle joint of each group of rats and the content of IL-1β and IL-18 in rat serum. Furthermore, immunofluorescence and qPCR methods were used to detect the protein and mRNA expression levels of NLRP3, caspase 1, ACS, and ASIC1a in the cartilage tissue of each group of rats.Results: Compared with the normal group, the right hind foot joint of the model group was significantly swollen, the levels of IL-18 and IL-1β in the serum of rats increased significantly, and the mRNA and protein levels of NLRP3, caspase 1, ACS, and ASIC1a in the chondrocytes also increased significantly. Compared with the model group, the degree of ankle joint swelling and IL-18 and IL-1β content in rat serum in each medication group was significantly reduced, and the combined group showed the greatest reduction compared with the other groups. After 8 weeks of treatment, compared with the model group, the mRNA and protein levels of NLRP3, caspase 1, ACS, and ASIC1a in the chondrocytes of each medication group were down-regulated. HE staining found that there were large numbers of infiltrating inflammatory cells and pannus in the joint tissue of the model group, while only a small amount of inflammatory cell infiltration and pannus was seen in the joint tissue of the rats in each treatment group. Conclusions:The method of Yiqi Yangyin Tongluo can attenuate the pyroptosis of RA chondrocytes through the ASIC1a/NLRP3 signaling pathway.