Depression, Lack of Efficacy Linked With DMARD Discontinuation in PsA

By year 5 of therapy with disease-modifying anti-rheumatic drugs (DMARDs), only about one-third of patients with psoriatic arthritis (PsA) were expected to be continuing with their therapy.

Patients who take biologic disease-modifying anti-rheumatic drugs (bDMARDs) for psoriatic arthritis (PsA) have a therapy retention rate of 70% after a year. However, this rate drops precipitously to 22% by 10 years, according to new research.

The study also found that the addition of methotrexate does not impact retention, but the presence of depression in the patient does have a negative effect. The study was published in Rheumatology International.

A number of studies have looked at the issue of therapy retention in patients with rheumatoid arthritis, but the authors said very little research has looked at retention in patients with PsA. The issue is important, they added, because a significant percentage of patients with PsA will discontinue their initial therapy, usually because of lack of efficacy; sometimes due to adverse events. In some cases, physicians have been encouraged to combine methotrexate with tumor necrosis factor inhibitors to boost retention, although the authors said that strategy remains controversial.

To better understand retention among people with PsA who are prescribed bDMARDs and the nonbiologic phosphodiesterase 4 inhibitor apremilast (Otezla), the investigators looked back at 159 patients with PsA who received treatment at a single health care center between 2000 and 2018. Each patient was prescribed at least 1 bDMARD or apremilast. Some patients were prescribed up to 8 DMARDs over the course of the study. The most common were etanercept (Enbrel; 34%) and adalimumab (Humira; 30%).

The investigators tracked primary and secondary failure, among other metrics. In most of the cases (96), therapy was discontinued, with the most common reasons being secondary failure (37%), primary failure (25%), and adverse effects (24%), the investigators found. The likelihood of a patient discontinuing their initial therapy was calculated at 37% after 5 years and 22% after 10 years. By 14 years, the retention rate was estimated to be 12%.

“The probability of continuing with treatment at 5 years was higher with etanercept and infliximab (Remicade), and the risk factors related to drug discontinuation were the number of swollen joints, male sex and, particularly, coexistence of depression,” the authors wrote.

Although 5-year retention was higher for etanercept, the longest overall retention seen in the study was for infliximab (6.2 years), followed by etanercept (4.5 years).

Methotrexate was found to be a nonfactor in retention of both bDMARDs and DMARDs, a finding that runs counter to some earlier research suggesting the addition of the drug was associated with better retention.

The authors said 1 limitation of their retrospective study was “major defects in the parameters used to evaluate disease activity.” As a result, they did not examine response to treatment, only the duration of treatment and the reasons for discontinuation. They said more research is warranted to more fully understand the issue.

Until then, the authors said these data show that this group of medications has a “remarkable” discontinuation rate in the first 5 years. They said physicians should closely monitor patients, particularly if they have risk factors like depression.

“Depression as a comorbidity has an important impact on the survival rate of treatments and should be taken into account in the multidisciplinary management of psoriatic disease,” they wrote.


Mateo Soria L, Prior-Español Á, Grigorov MM, et al. Long-term survival of biological therapy in psoriatic arthritis: 18-year analysis of a cohort in a tertiary hospital. Rheumatol Int. Published online Jun 30, 2021. doi:10.1007/s00296-021-04928-x