Patients with psoriatic arthritis (PsA) may soon have new treatment options: data on three drug trials show a large majority of study participants experienced significant benefit from the use of apremilast, brodalumab and ustekinumab – and with minimal side effects. The findings were presented (separately) at the 2013 Annual Congress of the European League Against Rheumatism (EULAR).
“For patients who suffer from psoriatic arthritis, they know as well as anyone that the drugs we have now have changed the face of the disease,” says Joseph F. Merola, MD, a rheumatologist and dermatologist at Brigham and Women’s Hospital in Boston. “But for certain individuals there is still the need for better first-line agents – and for others, we get to the end of the list of agents we run to and it can be difficult.”
Psoriatic arthritis (PsA) is characterized by skin lesions, or plaques, in addition to inflammatory arthritis. The National Psoriasis Foundation estimates up to 30 percent of people with psoriasis develop psoriatic arthritis. PsA can be treated with nonsteroidal anti-inflammatory drugs (NSAIDs), corticosteroids and disease modifying anti-rheumatic drugs (DMARDs), such as sulfasalazine and leflunomide. The efficacy of one DMARD commonly used for psoriatic arthritis, methotrexate, was called into question by a 2012 British study. Tumor necrosis factor-alpha inhibitors (TNF inhibitors) – a class of biologic drugs that includes adalimumab (Humira), etanercept (Enbrel), golimumab (Simponi), and infliximab (Remicade) – are also used to treat PsA.
But even these powerful drugs don’t help everyone. “We have a fairly substantial stable of people who either have tried three or four different [TNF inhibitors] and lost response, or never got a response in the first place,” says brodalumab investigator Philip J. Mease, MD, director of the Rheumatology Clinical Research Division at Swedish Medical Center in Seattle.
The new drugs work differently than TNF inhibitors (also called anti-TNFs) to control inflammation. Apremilast, taken orally, is a phosphodiesterase 4 (PDE 4) inhibitor. Brodalumab, taken by injection, targets interleukin 17 (IL-17). And ustekinumab, also taken by injection, inhibits interleukin 12 (IL-12) and interleukin 23 (IL-23). Ustekinumab, marketed as Stelara, has already been approved in the U.S. for plaque psoriasis.
The apremilast trial, a phase III study of 504 patients known as PALACE-1, looked at long-term effectiveness of the drug – an important measure, considering that PsA patients (like those with rheumatoid arthritis) sometimes see diminishing effects the longer a drug is used.
Patients were divided into three groups: a third received 30 mg of apremilast twice a day, a third received 20 mg of apremilast twice a day and a third received placebo. All patients taking one or more DMARDs (methotrexate, sulfasalazine and/or leflunomide) at stable doses at the start of the study were allowed to continue taking them.
The study found that at 16 weeks, up to 40 percent of patients on apremilast achieved ACR20 – which signifies a 20 percent reduction in swollen joint counts and improvement in associated symptoms – compared with 19 percent of patients taking placebo. At one year, up to 63 percent of apremilast users achieved or maintained ACR20.
The drug maker says it will submit a new drug application (NDA) with the U.S. Food and Drug Administration in 2013.
In the brodalumab trial, a phase II study of 168 people, up to 39 percent of patients achieved ACR20 after 12 weeks, compared to 18 percent of patients getting placebo.
Dr. Mease says that while the reduction in arthritis symptoms was “modest” in this trial (he notes that TNF inhibitors can get more than 50 percent of patients to ACR20), the effect on the skin was “amazing.”
“In the trial, patients were just blown away – just amazed – at the skin responses,” he says. In fact, using the benchmark Psoriasis Area and Severity Index, or PASI, as a response measure, up to 83 percent of patients using brodalumab achieved a 75 percent reduction in psoriasis symptoms and up to 63 percent achieved a 100 percent reduction at 12 weeks.
Data on the effect of brodalumab at 24 weeks hasn’t been published yet, but Dr. Mease says as the trial went on, more patients achieved ACR20 and saw reductions in their arthritis symptoms. Brodalumab will now move to phase III trials.
The ustekinumab trial, a phase III study known as the PSUMMIT 2, also looked at long-term effectiveness both in patients who had never used an anti-TNF and patients who had.
At 24 weeks, up to 44 percent of patients taking ustekinumab achieved ACR20 compared to just 20 percent on placebo. The drug’s effects were sustained after a year, with up to 56 percent of patients reaching ACR20. The drug worked best in patients who had never tried an anti-TNF (up to 73 percent reached ACR20) but it also worked in patients who had tried one (up to 55 percent reached ACR20), two (up to 39 percent) or three or more (up to 30 percent) biologics.
The manufacturer has asked the FDA to expand approval of ustekinumab to include the treatment of active psoriatic arthritis.