Comparative Effectiveness of Drug Therapies for Psoriatic Arthritis

Regulators in the UK have decided not to recommend apremilast as an alternative to DMARD therapy in patients with psoriatic arthritis.

Apremilast (Otezla) has demonstrated that it can ameliorate many symptoms of psoriatic arthritis for long periods of time, but a panel of British experts has concluded that its benefits are not sufficient to justify its use.

The National Institute for Health and Care Excellence (NICE) will recommend against using the medication in patients who cannot take or do not respond to disease-modifying antirheumatic drug (DMARD) therapy, which means the medication will not be available to National Health Service patients in England and Wales.

The decision has no direct effect on American physicians or patients, obviously, but it provides a serious attempt to compare the costs and benefits of the new drug with alternatives on the market. For example, NICE has approved the use of a wide range of non-steroidal anti-inflammatory drugs, which are often the first-line treatment for psoriatic arthritis, along with a number of DMARDs. For patients who fail on those, the organization has also recommended the use of newer and more expensive tumor necrosis facto (TNF) alpha inhibitors such as etanercept (Embrel), infliximab (Remicade), and adalimumab (Humira).

Carole Longson, the director of NICE’s Health Technology Evaluation Centre, said the organization sees definite value in more alternatives to TNF-alpha inhibitors.

“Around 10% of [psoriatic arthritis] patients stop TNF-alpha inhibitor treatment each year, either because it is contraindicated, or because of loss of effectiveness or adverse effects,” she said. “There is, therefore, a clear clinical need for a range of treatment options.”

However, apremilast simply did not perform well enough in trials to secure NICE approval.

“The committee considered the evidence on the use of apremilast both before and after TNF-alpha inhibitors and for people who aren’t able to take TNF-alpha inhibitors,” Longson said. “The committee concluded that apremilast is clinically effective compared with no other treatment. However, compared with TNF-alpha inhibitors, apremilast was the least clinically effective for treating psoriatic arthritis although some costs were saved by its use. Importantly, there was not enough robust evidence demonstrating that apremilast slows progression of the disease compared to TNF-alpha inhibitors. The committee concluded that they were unable to recommend apremilast for treating active psoriatic arthritis because the costs saved were not sufficient to justify the health losses.”

The most recent trial results on apremilast, pooled data from the PALACE 1, PALACE 2 and PALACE 3 trials, showed that the oral phosphodiesterase 4 inhibitor significantly reduced enthesitis and dactylitis in most patients for 2 years. Indeed, about 50% of patients in the 3 studies achieved a Maastricht Ankylosing Spondylitis Enthesitis Score (MASES]) of 0 and about 75% achieved a dactylitis count of 0.

However, all of the PALACE trials pitted apremilast — either 20 mg or 30 mg twice daily — against placebo (rather than TNF-alpha inhibitors) in patients who suffered active psoriatic arthritis after treatment with DMARDs. What’s more, participants were allowed to continue taking methotrexate, other DMARDs or DMARD combinations throughout the study period.

Collectively, patients who received apremilast 20 mg began the trials with a mean MASES of 4.6 and saw it drop an average of 55.1%. MASES dropped to 0 in 51.5% of the patients. The story was much the same for patients who received apremilast 30 mg. They started with a mean MASES score of 4.3 and saw a mean change of -57.5%. Scores fell to 0 in 48.7% of patients who were still taking apremilast at 54 weeks.

American physicians and patients do not appear concerned so far about any lack of evidence that apremilast stops disease progression as well as other medications. Celgene reported second quarter sales of $90 million for the drug, which is administered orally rather than via the injections required with TNF-alpha inhibitors.