Safety Data from RA Studies Doesn’t Always Apply to Psoriasis Patients

November 16, 2016

Safety results from studies of rheumatoid arthritis patients are not fully applicable to psoriasis patients, recent studies show.

Safety results from studies of rheumatoid arthritis patients are not fully applicable to psoriasis patients, according to a recent review of two large patient cohorts. The review found different outcomes and reactions to anti-tumor necrosis factor (TNF) therapy, with the rate of serious adverse events in rheumatoid arthritis patients almost double that of those with psoriasis, and with a different pattern of adverse events.

Biosimilars have been approved by the Food and Drug Administration for different rheumatology patient populations without testing the biosimilar on these patient populations, even though they are generally approved for all indications of the original drug. Information on the safety of TNF antagonists frequently arises from their use in rheumatic diseases, their first approved indications, and is later applied to psoriasis.

The question clinicians need to ask is whether safety results obtained in one group of rheumatologic diseases can be generalized to others.

The results of the review are not surprising, Jerry Bagel, M.D., director of psoriasis treatment center of New Jersey, told Rheumatology Network. “These are two different diseases and have different comorbidities, just as psoriatic arthritis is different from psoriasis. Rheumatoid arthritis has different manifestations, including nodules and uveitis. Psoriasis has more co-morbidities, including more obesity, fatty liver disease, and diabetes.”

Dr. Bagel also noted that in clinical trials rheumatoid arthritis patients are generally treated with methotrexate and systemic corticosteroids along with TNF antagonists. Psoriasis is more often treated with monotherapy, with no methotrexate or systemic corticosteroids. “Psoriasis patients usually do not receive any methotrexate, while half of rheumatoid arthritis patients have been on methotrexate and systemic corticosteroids,” he said.

“We can’t extrapolate on efficacy either,” Bagel added. “Just because a patient’s rheumatoid arthritis improves on a TNF antagonist, you can’t say the patient’s psoriasis will equally improve.”

The review set out to compare the safety profile of anti-TNF drugs in patients with rheumatoid arthritis and psoriasis to determine whether the risk of biological therapy is similar in these two diseases. The researchers used two national drug safety registries in Spain of patients with rheumatic diseases and psoriasis that include patients who started treatment with any biological agent.

Patients entering the registries were followed prospectively and evaluated at the time of an adverse event or a modification in the biological therapy. Only the TNF antagonists used in common between psoriasis and RA were included, namely infliximab, adalimumab and etanercept.

Among the 4,117 patients included in the review, there were far more with rheumatoid arthritis (3171 patients) than with psoriasis (946 patients). Patients with psoriasis were younger, and, as expected, there were more men in psoriasis cohort than in the rheumatoid arthritis cohort. The disease duration at starting biologics was shorter in rheumatoid arthritis than in psoriasis. There were no large differences in comorbidity at the start of therapy between the two groups, with the exception of more diabetes and hypercholesterolemia among the psoriasis patients than the rheumatoid arthritis patients.

Etanercept and adalimumab were the leading TNF antagonists used in both cohorts. Infliximab was more commonly used in patients with rheumatoid arthritis than in psoriasis. Biological agents were used in combination with methotrexate and corticosteroids more frequently in rheumatoid arthritis than in psoriasis.

The results show there were 1,248 serious or mortal adverse events in 16,230 person-years of follow-up in the rheumatoid arthritis cohort and 124 in the 2760 person-years of follow-up of the psoriasis cohort. Rates of serious adverse events were approximately doubled among rheumatoid arthritis patients (582.2 events per 1000 patient-years) compared with psoriasis patients (242.8 per 1000 patient-years). This risk remained after adjustment for sex, age, treatment, disease, hypertension, diabetes, hypercholesterolemia and simultaneous therapy with methotrexate, and after excluding patients receiving corticosteroids.

Patients with rheumatoid arthritis showed a higher rate of infections, cardiac disorders, respiratory disorders and infusion-related reactions, whereas patients with psoriasis had more skin and subcutaneous tissue disorders and hepatobiliary disorders.

Methotrexate could be a cause of the increased risk of adverse events among rheumatoid arthritis patients. However, the researchers pointed out that the effect of simultaneous therapy with methotrexate on the risk of serious events became nonsignificant on multivariable analysis, suggesting that methotrexate was not the cause of this increased risk in rheumatoid arthritis patients.

In conclusion, the researchers stated that “safety data from rheumatoid arthritis should not be fully extrapolated to psoriasis.” They suggested that both the disease and probably other unmeasured factors may play a role in the pattern of adverse events. They also noted that these differences are likely to apply to other immune-mediated inflammatory diseases (IMIDs).

The risk of adverse events varies according to the background disease and associated factors, the researchers stated. “The management of risk in IMIDs must take into account not only the risks inherent to the drug, but clearly also the interaction with disease characteristics, comorbidities and concomitant treatments,” they stated.

Bagel agrees that there are different adverse events with different patients according to their rheumatologic disease, and this can help clinicians choose the best therapy. “TNF antagonist exacerbations include demyelination, which can lead to the development of multiple sclerosis, Guillane berre syndrome, and optic neuritis, among others. “For any patient with a history of those demyelinating disorders or even a close family history, I would not use a TNF antagonist as first or second line therapy,” he said.

TNF antagonists can increase the risk of congestive heart failure (CHF). “If a patient had a history of CHF or Crohn’s disease or inflammatory bowel disease, and one of the demyelinating disorders, I would not use an anti-IL-17 agent. Instead, I might use ustekinumab,” said Bagel.  

Age should be another consideration in choice of therapy. “In general, elderly patients have more adverse events to biologic agents,” he said.

The results of clinical trials need to be examined closely. “Even with the same drug, there are usually different adverse events, including malignancies and serious infections, depending on what disease is being treated. Look at each different disease to understand the adverse events profile – we can’t extrapolate from one to another,” said Bagel.

 

References:

Garcia-Doval I, et al. Should tumour necrosis factor antagonist safety information be applied from patients with rheumatoid arthritis to psoriasis? Rates of serious adverse events in the prospective rheumatoid arthritis BIOBADASER and psoriasis BIOBADADERM cohorts. Br J Dermatolo 2016 Jun 3. DOI: 10.1111/bjd.14776.