Enbrel for Psoriasis May Alleviate Depression, Fatigue
December 23, 2005
The study, by Stephen Tyring, MD, of the University of Texas Health Science Center, and colleagues, was published in The Lancet and reported by MedPage Today on 15 December 2005.
In a double-blind, placebo-controlled trial involving 618 participants, 55% of patients receiving Enbrel showed significantly reduced symptoms of depression 12 weeks from baseline, compared with 39% of participants receiving placebo, according to MedPage Today.
Depression and fatigue commonly occur among people affected by psoriasis. The researchers noted that these conditions probably arise at least in part from the altered appearance of patients' skin, and by joint-pain in patients also affected by psoriatic arthritis.
However, increased concentrations TNF-alpha and other pro-inflammatory cytokines have been associated with depression, apart from psoriasis. Moreover, TNF-alpha has been linked with fatigue and sleepiness.
Psoriasis is mediated by TNF-alpha, which is inhibited by Enbrel. For this reason, Dr Tyring and colleagues examined whether Enbrel could affect depression and fatigue in a population of people with patients.
The study included 618 patients with mild to severe psoriasis. Half were randomized to receive placebo and half to receive Enbrel (50 mg) twice weekly for 12 weeks. The primary efficacy endpoint was a = 75% reduction from baseline in the severity of psoriasis symptoms. Secondary outcomes included a significant reduction in depression symptoms and fatigue.
At baseline, 26% of participants receiving placebo and 25% of participants receiving Enbrel had mild or moderate to severe depression, as rated by the Hamilton depression rating scale (Ham-D). Additionally, 35% of participants receiving placebo and 34% of participants receiving Enbrel had mild or moderate to severe depression as measured by the Beck Depression Inventory (BDI).
At week 12, key findings included:
- 47% of patients receiving Enbrel achieved a = 75% improvement in psoriasis symptoms, compared with 5% of participants receiving placebo (P<0.0001).
- 55% of patients receiving Enbrel had significantly reduced depression symptoms, compared with baseline, as measured by the BDI (compared with 39% of participants receiving placebo; P=0.0001).
- 43% of patients receiving Enbrel showed improvement in depressive symptoms, as measured by Ham-D (compared with 32% of participants receiving placebo; P=0.0048).
- Participants receiving Enbrel improved an average of five points on the Functional Assessment of Chronic Illness Therapy Fatigue (FACIT-F) scale (a three-point improvement on this 52-point fatigue scale is considered clinically significant) -compared with participants receiving placebo, who improved an average of 1.9 points (P<0.0001).
Tyring et al argued that the improvements in depressive symptoms were caused not only by disease-symptom reduction. They noted as an example that improvements on the Ham-D did not correlate well with psoriasis-symptom improvement, and that the correlation was insignificant (P=0.0848).
The researchers acknowledged that the study was not designed to detect a treatment effect on primary depression. "To study any such effect, it would be necessary to examine patients who did not have psoriasis but had been diagnosed with depression," they said, according to MedPage Today.
However, they concluded that "etanercept treatment might relieve fatigue and symptoms of depression associated with this chronic disease."
A main weakness of the study was the small number of participants who had moderate to severe depression, Jan D Bos, MD and John de Korte, MD, of the University of Amsterdam, wrote in an accompanying editorial. (Just 15% of participants receiving Enbrel had moderate to severe depression, as rated by the BDI, and only 2% as measured by the Ham-D; proportions among participants receiving placebo were similar).
"In future studies, it would be interesting to measure the effects of anti-TNF-alpha agents in patients with psoriasis with high levels of depression and fatigue," Dr Bos and Dr de Korte said, according to MedPage Today.
The study was funded by Immunex, which markets Enbrel.
Psoriasis Drug May Also Clear Up Depression and Fatigue, MedPage Today, 15 December 2005.
Etanercept and clinical outcomes, fatigue, and depression in psoriasis: double-blind, placebo-controlled randomized trial. Tyring S et al, The Lancet, advanced online publication, 15 December 2005.
Effects of etanercept on quality of life, fatigue, and depression is psoriasis. Bos JD and de Korte J, The Lancet. advanced online publication, 15 December 2005.
Posted: December 2005