An unexpected gender balance in the use of biological DMARDS for ankylosing spondylitis (AS) has piqued the curiosity of the PBAC’s Drug Utilisation Subcommittee (DUSC).
While epidemiological data suggest the disease is three times more common in males than females, DUSC found that males outnumber women only two to one among patients already on biologics, and the genders are equally balanced among patients commencing treatment.
“DUSC considered that the reason for this inconsistency between the literature and the PBS data was unclear and warranted further investigation,” their recent report on PBS use of the drugs concluded.
“A concern was that the unexpected gender ratio may reflect leakage into treatment of other inflammatory conditions.”
Infliximab was the first bDMARD listed on the PBS for AS, in 2004. It has been followed by etanercept, adalimumab, golimumab and, most recently, certolizumab pegol in 2014.
There’s been a corresponding increase in patients treated, from 628 in 2005 to 6,106 in 2014, with no sign of a plateau. The annual cost totalled $107 million in 2015.
More than 90% of patients have received a second approval for any bDMARD, reflecting a much higher continuation rate than suggested by the response rates of 47-58% seen in clinical trials.
The trials used ASAS20 responses as the criterion for success, but DUSC said that the PBS continuation criteria are similarly stringent.
Potential reasons for a higher than predicted total use include underestimation of the numbers of Australians with AS.
Higher retention on treatment might reflect a reluctance of clinicians and patients to withdraw treatment when there is only a partial response, particularly when there is a lack of alternative therapies, the DUSC report stated.
Treatment of earlier disease might also contribute, which DUSC considered “may be clinically appropriate” in light of recent data on the potential to slow radiographic progression.
Other reasons included increased familiarity with bDMARDs and improved awareness of inflammatory back pain.
A second report from DUSC found that about one in six patients starting a bDMARD for psoriatic arthritis have not fulfilled the PBS criteria for a prior trial of methotrexate and sulfasalazine or leflunomide.
While a trial is not required if these conventional DMARDs are contraindicated, the proportion not using the drugs appears to be increasing.
Contraindications must be stated when seeking an authority approval, but there has not yet been a comprehensive retrospective assessment of applications to check their accuracy.
“It is likely that only a minority of patients with psoriatic arthritis do not meet restriction criteria with regard to prior DMARD use,” the report stated.
Responses from AbbVie (adalimumab) and Janssen-Cilag (infliximab and golimumab) said the proportion not trialling the conventional DMARDs is probably appropriate .
The role of DUSC is to assess the projected use and financial cost of medicines, as well as collect data on actual use, and advise the PBAC.