One very important determinant of response to methotrexate…
Anxiety Prior To Methotrexate Therapy May Result In Non-Response At 6 Months
Reported in Healio… patients with rheumatoid arthritis who experience anxiety prior to the start of methotrexate therapy may have non-response at 6 months due to poor adherence, according to results presented at the EULAR Annual Congress.
“From a long list of lifestyle, clinical and psychosocial predictors at baseline, BMI, smoking and DAS28 score were each shown to significantly predict non-response 6 months after patients had started treatment with methotrexate,” Suzan Verstappen, of the Centre for Musculoskeletal Research at the University of Manchester, United Kingdom, said in a press release. “Of particular interest, however, is the role of participant anxiety on starting treatment with methotrexate in predicting response, which is likely to be the result of its negative effect on adherence.”
A workhorse drug for rheumatoid arthritis causing an excessive number of deaths in Australia
Eight Deaths Linked to Methotrexate in Australia
Dr. Jack Cush writing in Rheumnow reported methotrexate (MTX), a cornerstone drug used to treat rheumatoid arthritis (RA), has led to 90 hospitalizations and 8 deaths according to a recent report from the Medical Journal of Australia.
Many of these events were the result of inappropriate higher or more frequent doses than that prescribed. Such practices led to gastrointestinal tract ulceration, liver toxicity, bone marrow suppression, septicemia, and death.
In a nationwide search of MTX-related death rates, three datasets discovered that over 90 dosing error cases were reported from 2004 to 2015.
Twenty-two died from taking MTX, but only 7 deaths were directly attributed to overdosing. The United States Food and Drug Administration has noted 25 MTX deaths over a four-year timeframe.
The authors recommended changes in packaging and tablet appearance to reduce the incidence of these events.
Comment: Methotrexate is still the disease modifying drug of choice for rheumatoid arthritis. It has to be monitored though.
Methotrexate Safety with Chronic Hepatitis B Infection
Dr. Jack Kush writing in Rheum Now reported chronic liver disease, and in particular hepatitis B infection, is considered a contraindication to methotrexate (MTX) use.
Specifically, the package insert states, “Patients with psoriasis or rheumatoid arthritis with alcoholism, alcoholic liver disease or other chronic liver disease should not receive methotrexate.”
This issue has been studied further in a report from Nature researchers from Taiwan studied whether MTX use in RA patients with chronic HBV infection leads to liver cirrhosis.
They culled National Health Insurance Research Database in Taiwan and identified 631 incident cases of RA with chronic HBV – nearly half of whom were on MTX (358 MTX users and 273 MTX non-users).
A median of 6 years after the diagnosis of CHB, of all RA patients developed liver cirrhosis with no difference between those on or off MTX. They did not find any association between liver cirrhosis in CHB patients and long-term MTX use in RA. Furthermore, there was no occurrence of liver cirrhosis among 56 MTX users after 97 months’ treatment.
This population and claims based data failed to correlate long-term MTX use with an increased risk for liver cirrhosis among RA patients with chronic HBV.
What concerns about the fetus are there if a father is on disease modifying drugs? Next…
Children Whose Fathers Used DMARDs Not At Greater Risk Of Congenital Abnormalities.
Nancy Walsh writing for MedPage Today reported that according to a study published in the journal Arthritis and Rheumatology, “children whose fathers had inflammatory joint disease and used disease-modifying anti-rheumatic drugs (DMARDs) were not at increased risk of congenital abnormalities or other adverse outcomes.” After examining “data from the Medical Birth Registry of Norway and the Norwegian Disease Modifying Antirheumatic Drug registry, which began enrolling all patients initiating and/or stopping synthetic or biologic DMARDs in 2001,” researchers found that “among newborns whose fathers were exposed to DMARDs during the three months preceding conception, the relative risk of congenital malformations was 1.22, compared with healthy control fathers.” Essentially the same.
RA patients live longer than they used to … here is one reason
Mortality reduced in RA patients who maintained methotrexate therapy
Reported in Helio, an article published in Clinical and experimental rheumatology, researchers in Germany analyzed data on 271 patients with rheumatoid arthritis (RA; disease duration, 8.5 years) who had started methotrexate (MTX) treatment between 1980 and 1987. Modified American College of Rheumatology 20 (ACR20) response was used to measure response to MTX treatment 1 year after baseline. Follow-up data were available for 250 patients (mean age, 57.5 years; 78.4% women) up to 18 years.
Of those patients, 66% had a ≥20% response rate at 1 year (responders), 20% were considered nonresponders, and 14% had stopped MTX treatment because of lack of efficacy or adverse events including nausea, vomiting or stomatitis. Sixty-one percent of patients maintained MTX treatment at 10 years after baseline.
Responders had a 1.6 mortality ratio compared with a 3.2 ratio among nonresponders after 18 years.
Comment: By reducing systemic inflammation, there is a lower incidence of cardiovascular mortality.