2023-12-05 02:17:59
SAN DIEGO, USA. Monthly usage of secukinumab (Cosentyx) administered intravenously demonstrated its effectiveness compared to placebo in the treatment of psoriasic arthritis and axial spondyloarthritis in two randomized, double-blind, industry-sponsored Phase 3 trials for this second, recently approved route of administration of the drug.[1]
Studies of the human monoclonal antibody secukinumab, an interleukin-17 inhibitor, were presented at the 2023 American College of Rheumatology (ACR) Annual Meeting. There is a subcutaneous injectable presentation of the drug and the U.S. Food and Drug Administration United States (FDA) approved in October the intravenous presentation for the conditions indicated, although at a lower recommended monthly dose than in the new trials examined.
In the psoriatic arthritis trial, 191 patients received intravenous secukinumab and 190 received placebo.[1] For the primary endpoint, the percentages achieving at least a 50% improvement in the American College of Rheumatology (ACR50) response criteria at 16 weeks were 31.4% and 6.3%, respectively (p < 0,0001).
In the axial spondyloarthritis trial, 264 patients received intravenous secukinumab and 262 received placebo.[2] The primary endpoint, an improvement of at least 40% in the Assessment of the Spondyloarthritis International Society (ASAS40) response criteria, was met at 16 weeks in 40.9% and 22.9%, respectively (p < 0,0001).
“Both studies appear to show clear efficacy of intravenous secukinumab with no clear increase in evidence of adverse effects,” rheumatology specialist Dr. Nicola Goodson, PhD, of Aintree University, said in an interview. Liverpool Hospital, England.
“Offering intravenous administration as an option to patients is helpful,” added Dr. Goodson, who was not involved in the study but is familiar with its findings.
As he explained, secukinumab “was the first interleukin-17 inhibitor used to treat spondyloarthropathies and we have used subcutaneous secukinumab to treat psoriasis, psoriatic arthritis and axial spondyloarthritis or ankylosing spondylitis since 2016 in the UK. Our experience with this drug has been good, it has similar efficacy to that of treatment with tumor necrosis factor inhibitors in axial spondyloarthritis; is generally well tolerated and the subcutaneous pen injection device is easy for patients to use.”
However, he highlighted that intravenous treatment can accelerate the onset of action and may be useful in situations where therapeutic compliance is a challenge.
Psoriatic Arthritis Trial Details
In the trial INVIGORATE-2investigators enrolled patients who met CASPAR criteria for active psoriatic arthritis with symptoms for ≥6 months, with ≥3 tender joints out of 78 joints and ≥3 swollen joints out of 76.
Participants, 55% female and average age 48 years, were randomized 1:1 to receive placebo or secukinumab (6 mg/kg at baseline, followed by 3 mg/kg every 4 weeks). Those in the placebo group switched to the same monthly doses of secukinumab at 16 weeks.
“Patients who switched from placebo had an increase in efficacy similar to that seen in the originally treated group,” rheumatologist Dr. Alan J. Kivitz of the Altoona Center for Clinical Research in Duncansville said in his conference presentation. USA. At 52 weeks, the groups had similar ACR50 response rates: 58% with secukinumab and 64% with placebo and then secukinumab.
The fact that patients in the group that initially received placebo and then switched to a 3 mg intravenous dose without a 6 mg loading dose achieved similar ACR response rates as the secukinumab group throughout the trial “would suggest that the “IV loading doses may not be necessary. This would need to be explored in a randomized head-to-head study, but it is an interesting observation that may reduce costs and exposure to higher doses of medication at the start of treatment,” said Dr. Goodson.
Of patients who received secukinumab at any time during the study, 63% had a treatment-emergent adverse event, including 5.9% with serious adverse events. One death was reported in the placebo group before week 16. No other deaths were reported.
Axial Spondyloarthritis Trial Details
In the trial INVIGORATE-1, researchers recruited people aged 18 years or older with a diagnosis of active radiographic axial spondyloarthritis according to the modified New York criteria or non-radiographic axial spondyloarthritis according to the Assessment of the Spondyloarthritis International Society response criteria; all participants presented dorsalgia inflammatory condition for ≥6 months with onset before age 45 years. They were randomized 1:1 to receive intravenous secukinumab (loading dose of 6 mg/kg, followed by 3 mg/kg every 4 weeks) or placebo for 16 weeks. At that time, the placebo group was switched to the same monthly doses of intravenous secukinumab.
The participants had an average age of 39 years and a third were women.
Following the statistical superiority in ASAS40 response rates observed with intravenous secukinumab at week 16, patients who thereafter switched from placebo to intravenous secukinumab also had ASAS40 response rates equivalent to those of the originally randomized patients to secukinumab at week 24: 66.8% of those who received secukinumab all the time and 74.9% of those who changed.
Secondary endpoints were similar in both groups at week 52.
Of all patients in the secukinumab group, the percentage with any adverse effect was 63.2%, and 6% had a non-fatal adverse effect considered serious. There was one death during treatment with secukinumab that was not suspected to be related to treatment.
In a presentation on the results of the axial spondyloarthritis study, Atul Deodhar, MD, of Oregon Health & Science University, observed that “there are some advantages to having an intravenous biopharmaceutical in the United States. There are certain insurance providers in the United States. that it is more economical for the patient to have an intravenous drug.
Dr. Deodhar also mentioned that in October the US FDA approved a lower recommended dose for intravenous treatment than the study dose: 1.75 mg/kg instead of 3 mg/kg after the loading dose. This is because the 3 mg/kg dose reached higher blood levels than the subcutaneous form, he explained. The agency recommended the same dosage for psoriatic arthritis.
Limitations of the study
Dr. Goodson, a rheumatology specialist in the United Kingdom, noted a limitation of the trials: “It would have been interesting to compare intravenous secukinumab with subcutaneous secukinumab.” Still, the results indicate that “the tolerability and efficacy of intravenous administration appears equivalent,” she said.
“Intravenous application will have associated costs of attendance at the hospital or infusion clinics,” he added, “and the cost of additional staff and administration must be taken into account.”
Novartis, producer of secukinumab, funded both studies. The authors of the psoriatic arthritis study declared multiple industry relationships, and some, like Dr. Kivitz, have connections to Novartis. The authors of the axial spondyloarthritis study also disclosed multiple industry relationships, and some, like Dr. Deodhar, have connections to Novartis. Some authors of both studies are Novartis employees. Dr. Goodson disclosed financial relationships with UCB and AbbVie.
This content was originally published on MDedgepart of the Medscape Professional Network.
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