News in brief: Positive PBAC recommendation for narcolepsy drugs; Oral CRTH2 antagonist shows lacklustre effect on asthma; Should rituximab move up the line in SSc-ILD?

Positive PBAC recommendation for narcolepsy drugs

The PBAC has recommended extending the PBS listings of modafinil and armodafinil as first line treatments for patients with narcolepsy

At its May 2022 intracycle meeting the committee made the recommendation on a cost-minimisation basis to dexamfetamine.

“The PBAC considered that there was no clinical evidence to suggest that modafinil or armodafinil have superior comparative effectiveness or safety compared to dexamfetamine, and therefore considered that neither armodafinil nor modafinil should be more costly than dexamfetamine if they are to be listed for the first-line treatment of narcolepsy,” the decision summary stated.

The PBAC considered that the equi-effective doses are dexamfetamine 60 mg ≡ modafinil 400 mg ≡ armodafinil 250 mg.

Oral CRTH2 antagonist shows lacklustre effect on asthma

The oral CRTH2 antagonist timapiprant “had little impact” on clinicopathological changes induced by rhinovirus (RV) infection in poorly controlled asthma, a study has shown.

On the back of previous positive data on CRTH2 antagonists in asthma, a research team lead by Dr Hugo Farne, National Heart and Lung Institute, Imperial College London, sought to determine whether timapiprant reduced or prevented asthma exacerbations induced by experimental rhinovirus (RV) infection.

For the study, atopic patients with partially controlled asthma taking maintenance inhaled corticosteroids were randomised to receive either timapiprant or placebo, and challenged with RV 3 weeks later. The primary endpoint was the cumulative lower respiratory symptom score over the 14 days after infection.

Published in Thorax, the data showed no difference between the two groups (timapiprant n=16, placebo n=14) in clinical exacerbation severity, including cumulative lower respiratory symptom score day 0-14 (p=0.78), viral load, antiviral immune responses, or most RV-induced airway inflammation.

The authors said they believe it “unlikely the lack of effect observed in this study was due to choice of drug, as there is no evidence to suggest timapiprant is less efficacious than any other CRTH2 antagonist”.

Instead, there are several more plausible explanations, they noted, including that participants had moderate rather than severe asthma and that exacerbations were relatively mild, so there may not have been sufficient inflammation to detect a drug effect.

The authors also argued that perhaps just a subset of patients with type 2 asthma benefit from CRTH2 antagonist treatment, which were not sufficiently represented in the study to generate a significant result. “Alternatively, CRTH2 blockade may not offer additional benefits over and above ICS which are potent immunosuppressive agents,” they added.

A Phase 3 trial of timapiprant in asthma is ongoing.

Should rituximab move up the line in SSc-ILD?

Rituximab may stabilise lung function and delay deterioration in patients with progressive SSc-ILD, Australian clinicians have noted.

A retrospective WA case series comprised 13 patients treated with rituximab between 2008 and 2019 after deterioration of lung function despite standard therapy.

“The mean baseline FVC (%) and DLCO (%) immediately prior to rituximab were 57.18 and 37.10 respectively, indicating that this group of patients had significantly impaired lung function.”

The review found all patients demonstrated stability of lung disease at 12 months following one cycle of rituximab, consistent with several other studies.

“As interstitial lung disease is a progressive and fatal complication of SSc, preventing further disease progression is a meaningful outcome. This raises the question as to whether rituximab should be incorporated earlier into standard treatment regimens following the diagnosis of SSc-associated ILD rather than as an adjunct in the setting of failure of, or contraindication to, mycophenolate or cyclophosphamide,” said Dr Kelly Morgan and colleagues from the Department of Rheumatology, Fiona Stanley Hospital, Perth.

Read more in the Internal Medicine Journal

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