B-cell-depleting Therapies May Increase Risk of Psoriasis
Reports of psoriasis — an autoimmune skin disease that shares some biological processes with multiple sclerosis (MS) — are disproportionally high among MS patients on therapies that deplete B-cells, according to a U.S. study based on patient adverse event data.
Conversely, patients on Tysabri (natalizumab), glatiramer acetate (sold as Copaxone, among others), or dimethyl fumarate (sold as Tecfidera and others) were significantly less likely to report psoriasis as an adverse event.
Further studies are now needed to confirm the link between B-cell-depleting therapies, including rituximab (sold as Rituxan, among others) and Ocrevus (ocrelizumab), and the increased the risk of psoriasis and to better understand its underlying mechanisms.
This information may help determine whether certain disease-modifying therapies (DMTs) should be avoided in MS patients with psoriasis or at risk of developing the skin disease, the researchers noted.
The study, “Disproportional increase in psoriasis reports in association with B cell depleting therapies in patients with multiple sclerosis,” was published in the journal Multiple Sclerosis and Related Disorders.
Skin-related autoimmune conditions have been reported in MS patients on DMTs. Psoriasis, one of those conditions, is characterized by itchy, red, and dry patches of skin. It shares some underlying processes with MS and has been suggested as a potential risk factor for future MS.
However, the exact relationship between MS and psoriasis remains unclear.
“Since various DMTs have different therapeutic targets, it may be possible that certain DMTs may either protect or induce and unmask psoriasis,” the researchers wrote.
With this in mind, a team of researchers in the U.S. assessed the occurrence of psoriasis in people receiving different MS DMTs by analyzing adverse reports in the U.S. Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database and OpenFDA.
FAERS is a publicly available database that contains de-identified adverse event and medication error reports submitted voluntarily by patients and healthcare providers to the FDA. OpenFDA is an online tool that facilitates statistical analyses of FAERS data.
Psoriasis reports in MS patients were collected for each DMT between Jan. 1, 2009, and June 30, 2020. The approved DMTs Mavenclad (cladribine), Mayzent (siponimod), and Zeposia (ozanimod) were excluded from the analysis due to minimal or no psoriasis reports. Included cases were arranged based on age, sex, and report source.
Results showed that of the 45,547 skin-related conditions reported in FAERS, 514 (1.13%) were of psoriasis. Reports of other autoimmune skin diseases were minimal (up to 33 reports per disease) for all DMTs.
Patients initiated the reporting of psoriasis for most DMTs except for glatiramer acetate and rituximab, “which had more healthcare professional driven reports,” the researchers wrote. Also, reports of female patients surpassed those of male patients for all DMTs except for Lemtrada (alemtuzumab).
The highest proportions of psoriasis reports were noted for rituximab (6.5%) and Ocrevus (3%) while the lowest proportions were detected for glatiramer acetate, teriflunomide (sold as Aubagio with generics also available), Lemtrada, and dimethyl fumarate — all less than 1%.
In addition, a statistical analysis of the 302 total psoriasis reports retrieved by OpenFDA showed that patients treated with rituximab were seven times more likely to report psoriasis as an adverse event.
According to OpenFDA results, psoriasis reports were also significantly more frequent among Ocrevus-treated patients (by nearly fourfold) and those receiving Gilenya (fingolimod; by 1.3 times). In turn, the likelihood of reporting psoriasis while on a DMT was significantly lower (by 29–47%) with Tysabri, glatiramer acetate, and dimethyl fumarate.
When analyzing by sex, Tysabri was the only DMT associated with a significantly lower likelihood of psoriasis reports in both females and males.
Rituximab, Ocrevus, and Gilenya significantly increased the likelihood of psoriasis reporting in females, but only Ocrevus reached statistical significance in males. This may be partly related to the fact that there was only one report of psoriasis with rituximab in male patients, the team noted.
Overall, these findings suggest that rituximab and Ocrevus may increase the risk of psoriasis in MS patients.
Rituximab is often used off-label for the treatment of MS, and Ocrevus is the only therapy approved for primary progressive MS, in addition to relapsing forms of the disease. Both therapies work by promoting the death of B-cells, a type of immune cell implicated in the abnormal immune attacks that drive neurodegeneration in MS.
While the mechanisms by which B-cell-depleting therapies may increase the risk of psoriasis are unclear, rituximab has been reported to increase type 1 interferon in some patients with another autoimmune disease.
Since type 1 interferon is key for the development of psoriasis, further studies are needed to assess whether Ocrevus has the same effect and identify the underlying mechanisms of this potentially increased risk of psoriasis in some patients on B-cell-depleting therapies.
As for the DMTs showing potentially “protective” effects against psoriasis, glatiramer acetate, dimethyl fumarate, and Aubagio are known to reduce immune cell activation and/or promote a shift toward anti-inflammatory responses, which may prevent psoriasis.
In turn, Tysabri prevents circulating immune cells from reaching the brain and spinal cord, and the mechanisms by which it may protect against the autoimmune skin disease need additional evaluations, the team noted.
Future studies are needed to “determine if certain DMTs should be avoided in MS patients with [simultaneous] psoriasis while others may be a better choice for individuals affected by, or at high-risk for developing psoriasis,” the researchers wrote.
In addition, “careful monitoring and reporting of psoriasis as a possible side effect of some DMTs is needed,” the team concluded.