PLUS: Abatacept shortages; Lilly pulls plug on baricitinib for lupus; ORAL Surveillance data published; and FDA approves new JAKi indications.
PLUS: Abatacept shortages; Lilly pulls plug on baricitinib for lupus; ORAL Surveillance data published; and new FDA approvals for PsA and AS.
In its latest update to the living guidelines, Australia’s National Covid Clinical Evidence Taskforce recommended antiviral combination therapy Paxlovid (nirmatrelvir plus ritonavir) for use in unvaccinated adults who have had covid symptoms for five days or fewer but are at risk of severe disease, which includes people on immunosuppressant medications.
The Taskforce said that the drug “probably” decreases the risk of hospitalisation, but only in people who are unvaccinated, not on oxygen, and developed symptoms no more than five days ago. However, in the case of immunocompromised patients, it says, physicians could consider using it regardless of vaccination status.
Sotrovimab is also generally not recommended for fully vaccinated patients – unless they’re immunosuppressed.
If other medications such as Paxlovid or sotrovimab are not suitable or unavailable, the Taskforce has recommended molnupiravir be used. However, it noted that there was only limited evidence of the drug’s efficacy, especially against the Omicron variant, and safety. Furthermore, its efficacy in vaccinated or immunocompromised patients is unknown.
The ACR has also updated its vaccination recommendations, including supplemental and booster vaccine dosing and DMARD withholding periods.
Abatacept SC shortage
Bristol-Myers Squibb has reported a shortage of SC forms of abatacept (Orencia), with prefilled syringes and autoinjectors currently out of stock in Australia.
The prefilled syringe will be unavailable throughout February, and the autoinjector (ClickJect) throughout February until late March. Ongoing disruption is expected throughout the first half of the year. Supplies of IV Orencia are currently unaffected.
Baricitinib lupus development to be discontinued
In what rheumatologists have described as sad news, Lilly and partner Incyte have announced they’re pulling the plug on baricitinib (Olumiant) for lupus.
The drug met its primary endpoint in the SLE-Brave-I study, with a statistically significant reduction in disease activity at 52 weeks. However, the drug failed to meet the primary endpoint in the second trial, SLE-Brave-II. Secondary endpoints were missed in both studies, Lilly reported in a press release.
The company says it’s working with investigators to wrap up the phase 3 long-term extension trial, SLE-BRAVE-X.
🚨 SAD LUPUS NEWS
— Laurent ARNAUD (@Lupusreference) January 28, 2022
Based on results from two pivotal Phase 3 trials in systemic #Lupus (SLE-BRAVE-I and II), Lilly has decided to DISCONTINUE the Phase 3 development program for #baricitinib in #SLE 😭https://t.co/XWgv5OmLrM
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ORAL Surveillance data published
Data from the ORAL Surveillance on CV and cancer risk in RA patients has been published in the New England Journal of Medicine and the ACR has issued an updated statement on JAKi boxed warning. The data was also presented at the 2021 ACR convergence.
In an accompanying editorial, Jasvinder Singh, professor of epidemiology and medicine at the University of Alabama at Birmingham, pointed out that while it’s unclear as to whether the differences in CV outcomes are due to protective effects of TNFi or increased risk of tofacitinib, this doesn’t change the risk-benefit analysis in choosing between the two drugs for patients.
Similarly for cancer, which is also listed as a black-box warning for TNF inhibitors, the slight increase in risk with tofacitinib makes it a “nonpreferred drug” for RA patients with previous or current cancer, or who are at risk of cancer.
Professor Singh noted that the ORAL Surveillance findings don’t apply directly to patients under 50 years of age and those over 50 with no additional CV risk factors. He concluded that effective treatment of RA is critically important and any increase in risk must be balanced against patient preferences for oral medication.
New FDA approvals for PsA and AS
JAK inhibitors upadacitinib (Rinvoq – AbbVie) and tofacitinib (Xeljanz – Pfizer) were recently approved for new indications by the FDA, as was IL-23 blocker risankizumab (Skyrizi – AbbVie).
Upadacitinib is now approved in the US for adults with active psoriatic arthritis who have had an inadequate response or intolerance to TNF inhibitors. Approval was based on data from the SELECT – PsA 1 and SELECT – PsA 2 trials, where it met the primary endpoint of ACR20 response at week 12. It was approved in Australia for this indication in May last year.
Also approved was tofacitinib for adults with active ankylosing spondylitis who have had an inadequate response or intolerance to TNF inhibitors, making it the first JAKi to obtain regulatory approval for five indications in the US. Approval was based on a phase 3 placebo-controlled efficacy and safety trial.
Risankizumab is now approved for PsA, having previously been approved for plaque psoriasis. The approval was based on results of the phase 3 placebo-controlled KEEPsAKE 1 and KEEPsAKE 2 trials. The drug is currently approved for plaque psoriasis in Australia.
