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Duke Health release earns applause for clear disclosure, but we wanted more info on harms and cost associated with this eye treatment

Newswise — DURHAM, N.C. — Patients suffering from noninfectious uveitis, a group of diseases that causes eye inflammation, can get effective treatment from a corticosteroid alternative that has previously been approved for treatment of arthritis and Crohn’s disease, according to a study led by a Duke Health researcher.

The Food & Drug Administration recently approved the additional use of adalimumab (sold as Humira) for patients with noninfectious uveitis. Corticosteroids have traditionally been the only FDA-approved treatment for these diseases, although some doctors had prescribed adalimumab off-label.

The FDA’s approval is limited to treatment of the three types of noninfectious uveitis that pose the greatest threat of vision loss.

Glenn Jaffe, M.D., a professor in the Department of Ophthalmology at Duke University School of Medicine, said adalimumab works to treat uveitis by targeting a protein that is thought to promote inflammation. Jaffe led one of two clinical studies that formed the basis of the FDA’s approval and was senior author of the study appearing Sept. 8 in the New England Journal of Medicine (NEJM).

“Patients may have many unwanted side effects when taking steroids long-term, as many uveitis patients do,” Jaffe said. “The goal of these studies was to determine whether there was an alternative that could replace or minimize the use of steroids. The studies also looked at whether an alternative would be better tolerated or more effective, yet still safe.”

The study consisted of 217 adults who had active, non-infectious intermediate or posterior uveitis, or panuveitis. Participants were randomly assigned to a group that received either adalimumab or a placebo at the start of the trial and every two weeks thereafter. All participants also initially received standard doses of the corticosteroid prednisone, and continued to receive it in diminishing doses over the course of 15 weeks.

Jaffe and colleagues then analyzed patients’ time to treatment failure, or how soon they saw a recurrence or worsening of one or more of four signs of inflammation: new areas of inflammation in the back of the eye, reduced visual clarity, more inflammatory cells in the front of the eye, or more cloudiness of the gel that fills the eye. Jaffe said the study focused on time to treatment failure because delaying or preventing inflammation is the key to successful treatment.

“It is the active inflammation, caused by the body’s immune system reacting against itself, that can potentially permanently decrease the patient’s vision and cause unwanted symptoms, such as eye pain and floaters in the field of vision,” he said. “The hope is that by delaying or eliminating recurrences, the symptoms will be minimized or eliminated.”

The researchers found that median time to treatment failure was 24 weeks in the adalimumab group and 13 weeks in the placebo group. Patients in the adalimumab group were also significantly less likely to experience treatment failure during the duration of the study (80 weeks) and they were at lower risk of treatment failure due to each of the four signs.

Jaffe said the study’s results are significant not only because they indicate adalimumab delays treatment failure, but also because the investigation considered several signs as causes for treatment failure.

“Using these multiple, possible endpoints was something unique to this study,” Jaffe said. “Since each of these signs can be associated with different types of uveitis, the study’s results broaden the applicability of treatment for patients.”

The study authors note, however, that patients in the adalimumab group reported serious adverse effects, such as respiratory tract infections and allergic reactions, more frequently than those in the placebo group.

In addition to Jaffe, co-authors include Andrew D. Dick, Antoine P. Brézin, Quan Dong Nguyen, Jennifer E. Thorne, Philippe Kestelyn, Talin Barisani-Asenbauer, Pablo Franco, Arnd Heiligenhaus, David Scales, David S. Chu, Anne Camez, Nisha V. Kwatra, Alexandra P. Song, Martina Kron, Samir Tari, and Eric B. Suhler.

AbbVie, the pharmaceutical company that manufactures and markets adalimumab as Humira, sponsored the study. Dr. Jaffe served as a consultant for AbbVie, and other study authors also report financial relationships with the company. Further author disclosures are available in the study’s manuscript.

Humira Provides Effective, Non-Steroid Alternative for Eye Inflammation

Our Review Summary

Red human eyeA study of 217 people afflicted with an eye disease called uveitis tried to determine just how well adalimumab, a pricy “biologic” drug, could stave off frustrating symptoms like inflammation inside the eye, floaters, cloudy vision, and blurred vision. Every patient received standard daily injections of a corticostroid called prednisone, but half were also given a placebo injection, and half were given injections of adalimumab, which is FDA-approved to treat other diseases. Adalimumab held uveitis at bay for 24 weeks, or nearly twice as long as the control group at 13 weeks. But that extra uveitis symptom control came with two costs: a significant uptick in “severe adverse events” and a treatment that costs 50 times more than the one it supplemented.

The study published in the NEJM was one of two that supported FDA approval of the drug for uveitis. As this news release clearly points out, the study was sponsored by the company that sells the drug and many of the authors served as paid consultants to the company.

The Duke Medicine-issued release about the study also grasped the benefits and quality of the evidence very well.

 

Why This Matters

Uveitis, or inflammation of and damage to important structures in the eye, is a relatively rare disease that affects about 43,000 new people a year in the United States, according to the Ocular Immunology and Uveitis Foundation. While treatable, left untreated it was once a leading cause of blindness worldwide.

Most people are treated with daily injections of a corticosteroid called prednisone. However, steroids like prednisone, used long-term or sometimes only briefly, can lead to diabetes, osteoporosis, and even psychological changes, since they not only only dial back inflammation, but also affect the body’s metabolism. So any drug that can more specifically target the inflammation seen in the eyes of uveitis patients could cut back these risks and improve treatment efficacy.

Adalimumab (marketed as Humira) is approved for several other immune system diseases including psoriasis, arthritis and Crohn’s disease. Although adalimumabit is not a cure for those diseases or for uveitis, it is an alternative to steroids. That said, the drug comes with side effects, many of which have to do with its action in suppressing the immune system which increases the risk of infections and cancer.

Criteria

Does the news release adequately discuss the costs of the intervention?

Not Satisfactory

No dollar signs here, which — as we discovered — is quite an oversight, given the steep costs of adalimumab.

Prednisone costs about $0.33 per mg, and chronic uveitis patients take anywhere from 10 mg to 60 mg per day. Looking at the minimum number (which patients are usually tapered to 6 months into their treatment), that’s a cost of more than $1,190 a year.

In comparison, the name-brand of adalimumab, Humira, costs about $54.49 per mg. In the study, patients received adalimumab on a bi-weekly basis, receiving some 1,640 mg of the drug over 80 weeks if they didn’t drop out. That adds up to a total of $89,400 — an average of $58,000 per year or $1,120 per week.

Does the news release adequately quantify the benefits of the treatment/test/product/procedure?

Satisfactory

The benefits are well-represented in the release, and so is their context. By working adalimumab into the standard treatment, most of the key measurements of uveitis are held in check for nearly twice as long in a typical patient — 24 weeks instead of 13 weeks.

This represents improvement — but not a cure — for a chronic disease.

Does the news release adequately explain/quantify the harms of the intervention?

Not Satisfactory

The harms covered in the study were glossed over in the release, in particular by this sentence: “[P]atients in the adalimumab group reported serious adverse effects, such as respiratory tract infections and allergic reactions, more frequently than those in the placebo group.”

Given what was left out, we’ll mark this one unsatisfactory.

What’s not mentioned is that 16% patients in the adalimumab group dropped out compared to less than 7% in the placebo group. We also learned that some of the adverse events that triggered dropout weren’t included in the release: “Adverse events leading to discontinuation of participation in the trial were more common in the adalimumab group and included choroidal neovascularization, blurred vision, reduced visual acuity, fatigue, malaise, and suicidal ideation.”

Something simple that the release could have characterized about the adalimumab treatment’s harms, but didn’t: it had three times the rate of “adverse events” and twice as many serious adverse events.

Including any of these numbers — and some of the harms that taking corticosterids like prednisone can cause (the best we get is “many unwanted side effects”) — would have put the harms and benefits of the adalimumab treatment into clearer context.

Does the news release seem to grasp the quality of the evidence?

Satisfactory

This is perhaps the greatest strength of the release. It not only clearly explains the reasons for the drug trial and the metrics of measurement, but also the activity through which the drug might work.

The report involves a randomized controlled trial, so a strong evidence level is expected, and the release did note the industry sponsorship. It’s well known that studies sponsored by industry report favorable results more frequently, which makes some sense, in that companies wouldn’t test drugs they didn’t have strong preliminary evidence for. But it’s also possible that industry sponsorship can bias the conduct and reporting of such studies to make a positive outcome more likely.

Does the news release commit disease-mongering?

Satisfactory

We couldn’t find anything that would scare a reader. In fact, the release perhaps went a little too far to the other end of the spectrum and didn’t mention the word “blindness” once, which is a possible outcome of uveitis if left untreated.

Does the news release identify funding sources & disclose conflicts of interest?

Satisfactory

The release dedicates a whole paragraph to summarizing potential conflicts of interest, which is welcome and we hope to see this kind of transparency showing up in more releases in the future. It further directs readers to the published study’s supplementary documents for more extensive disclosure information.

In the PDF of supplementary materials we learned that only two out of the 17 authors had no conflicts of interest to declare.

Does the news release compare the new approach with existing alternatives?

Not Satisfactory

Although the release mentions the weakness of corticosteroids in uveitis treatment, it doesn’t go far enough in explaining how steroids compare with adalimumab, even though steroids were given to the patients concurrently with adalimumab in “diminishing doses” throughout the trial.

It’s worth noting, especially for comparison with adalimumab, how the long-term use of corticosteroid drugs work against uveitis symptoms by suppressing the body’s entire immune system — and, as a side effect, metabolism — not just one specific target of inflammation. Humira also suppresses the body’s immune system although through a different mechanism.

Does the news release establish the availability of the treatment/test/product/procedure?

Satisfactory

The level of detail is good here, noting that the FDA recently approved adalimumab for noninfectious uveitis, how it was previously approved for other conditions, and in which types of uveitis it’s generally ok to treat.

Does the news release establish the true novelty of the approach?

Satisfactory

The novelty is somewhat nuanced, but explained well enough: Uveitis is a bag full of symptoms, and the damage involved can span across the entire eye. By measuring how it affected the most frequent symptoms, “the study’s results broaden the applicability of treatment for patients” and possibly help lead to longer-term solutions for uveitis.

Total Score: 7 of 10 Satisfactory

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