Atorvastatin for the Treatment of Plaque-type Psoriasis

Toktam Faghihi, Mania Radfar, Zohre Mehrabian, Amir Hoshang Ehsani, and Mohsen Rezaei Hemami,

Disclosures

Pharmacotherapy. 2011;31(11):1045-1050. 

In This Article

Discussion

To our knowledge, this is the first double-blind trial evaluating the efficacy and safety of atorvastatin for the treatment of plaque-type psoriasis. Improvement of psoriasis lesions from statins is expected due to their antiinflammatory and immunomodulatory effects similar to current systemic therapies for psoriasis such as biologic agents and methotrexate.[1] Statins decrease adhesion molecules and chemokine receptors and attenuate leukocyte activation and migration.[3]

In corroboration of these immunomodulatory functions of statins, an open-label study demonstrated a significant improvement of psoriasis in seven patients treated with simvastatin 40 mg/day for 8 weeks.[23] Patients had BSA involvement greater than 10% and PASI scores greater than 12 at baseline, and topical therapy with emollients and low-potency corticosteroids was allowed. Recently, in a double-blind, placebo-controlled trial, oral simvastatin proved to be effective in the treatment of psoriasis when added to topical betamethasone.[24]

In contrast, another study does not confirm the results from the above-mentioned trials. In this open-label study, five patients with a mean PASI score of 11.4 received oral simvastatin for 12 weeks.[25] The patients were also receiving concomitant calcipotriol and corticosteroids. No significant change in PASI score was observed.

In our study, we observed significant improvement in psoriasis lesions in patients assigned to atorvastatin as well as in the placebo group. This therapeutic benefit, however, may be attributed to the effects of emollients and the standard topical therapies applied concomitantly.

Based on the results of this study, no statistically significant differences were noted between the two treatment groups in mean PASI score, percentage BSA involvement, and PASI 75. This could be attributed to the lower baseline PASI scores of our study patients. It should be emphasized that we included patients with psoriasis based on the United States Food and Drug Administration definition of BSA involvement of at least 10% as a determinant of severe disease.[26] This resulted in inclusion of participants with lower baseline PASI sores compared with other trials evaluating new drugs administered systematically. The mean ± SD baseline PASI scores in our study were 7.42 ± 1.90 and 6.92 ± 1.76 in the atorvastatin and placebo groups, respectively. Thus, since our participants were also receiving concomitant standard topical therapies, a larger sample size was required to detect a significant difference in this setting. Also, positive results might have been noticed by enrolling patients with higher PASI scores. However, in one of the abovedescribed studies,[25] no significant change in PASI was observed despite participants' mean PASI score of 11.4. As mentioned, the patients were also receiving concomitant calcipotriol and corticosteroids.[25]

The lipid-lowering effects of statins are a wellconsidered class effect. However, it is still debated whether the pleiotropic properties are also a consistent class effect.[27] For instance, atorvastatin is associated with more benefits than simvastatin or other statins in the early management of patients with acute coronary syndromes.[28,29] As a result, we assumed that in plaque psoriasis, clinical benefits would be likely to occur with atorvastatin since some benefits have been reported for simvastatin.[23] Failure to document such a benefit with atorvastatin in this study further emphasizes the need for designing clinical trials evaluating atorvastatin efficacy in patients with psoriasis who have more intensive disease as characterized by high PASI scores. It is also probable that higher atorvastatin doses, rather than 40 mg/day, may offer significant disease improvement.

In our study, after 12 weeks, 40% of atorvastatintreated patients attained PASI 75 response compared with 35% of the placebo group (p=0.204). One randomized trial comparing the efficacy and safety of adalimumab versus methotrexate and placebo in patients with moderate-to-severe plaque psoriasis reported a PASI 75 response rate of 80% for patients receiving adalimumab, 36% for methotrexate, and 19% for placebo after 16 weeks of therapy.[30,31] It seems that atorvastatin has achieved a comparable effect to that of methotrexate. However, in our trial, the study population comprised patients with low baseline PASI scores who also received topical therapy according to study protocol. Thus, the improvement in both treatment groups can be ascribed to concomitant topical therapies. Likewise, a PASI 75 response rate of 34% has been reported for betamethasone dipropionate (a class V corticosteroid) when used in patients with a mean baseline PASI score of 8.2.[32] Response may be attributed to the fact that all patients underwent a washout from their psoriasis treatments.

The limitations of our study include the low PASI score of the patients and the small study population, although it is one of the largest double-blind, placebo-controlled trials with statins on this topic. We also did not consider quality-of-life issues, which are the most important determinants of disease severity.[26]

Comments

3090D553-9492-4563-8681-AD288FA52ACE
Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.

processing....