In the Journals

TNF inhibitor dose reduction noninferior to full dose in ankylosing spondylitis

Jordi Gratacós

Reduced doses of TNF inhibitor therapy were noninferior to full doses in maintaining low-disease activity after 1 year in a cohort of patients with ankylosing spondylitis, according to data published in Arthritis Research & Therapy.

“In our study, we could reduce approximately half of the doses of TNF inhibitors,” Jordi Gratacós MD, PhD, of the Department of Rheumatology at Parc Taulí Hospital in Barcelona, Spain, told Healio Rheumatology in an interview. “Overall, the impact to the implementation of a strategy of TNF inhibitor dose reduction on public health budgets could be enormous without any impact on clinical outcomes.”

To assess if a dose-reduction strategy for TNF inhibition could be used without compromising efficacy or inducing unwanted safety outcomes, Gratacós and colleagues conducted a randomized, open-label multicenter clinical trial in a cohort of 126 patients, 113 of whom were included in the main per-protocol subset. Key eligibility criteria included clinical remission for 6 months or more after undergoing treatment with adalimumab (Humira, Abbvie), etanercept (Enbrel, Amgen), infliximab (Remicade, Janssen) or golimumab (Simponi, Janssen).

 
Reduced doses of TNF inhibitor therapy were noninferior to full doses in maintaining low-disease activity after 1 year in a cohort of patients with AS, according to data.
Source: Adobe

According to the researchers, noninferiority in terms of low-disease activity (LDA) at 1 year occurred in 81.3% of 58 patients in the reduced dose arm and 83.8% of 55 patients in the full-dose arm. The researchers reported an adjusted dose difference of 2.5% (95% CI, 16.6 to 11.7).

Safety data showed serious adverse event rates of 3.3% in the reduced-dose arm and 11.3% in the full-dose arm (P = .164).

“Although the noninferiority limit was only demonstrated for LDA, the results were statistically no different and consistent across many variables and TNF inhibitor drugs, confirming the robustness of the data we presented,” Gratacós said. “Serious adverse events and infections were nominally less than one-third in the reduced-dose group as compared to full dose, although not significant. This could suggest that low TNF inhibitor doses might have a better safety profile, but confirmation is needed, since the size and duration of our study were insufficient to draw conclusions.”

Gratacós indicated that these findings could have relevance for clinical practice in terms of both cost and safety. “The direct costs linked to TNF inhibitor treatments is the most limiting factor for extending this treatment to all patients who need it,” he said. “Moreover, it seems to be long-term treatments, so the impact of these treatments on the budget of health public systems is enormous.”

Regarding safety, Gratacós suggested that the low number of severe events in the reduced dose arm may be important, “especially since these are long-term treatments for often-fragile patients,” he said. – by Rob Volansky

Disclosure: Gratacós reports receiving financial support to attend congresses and/or collaborating in work meetings and/or participating in papers financed by: AbbVie, Amgen, Celgene, Janssen, Novartis, and Pfizer Inc.

Jordi Gratacós

Reduced doses of TNF inhibitor therapy were noninferior to full doses in maintaining low-disease activity after 1 year in a cohort of patients with ankylosing spondylitis, according to data published in Arthritis Research & Therapy.

“In our study, we could reduce approximately half of the doses of TNF inhibitors,” Jordi Gratacós MD, PhD, of the Department of Rheumatology at Parc Taulí Hospital in Barcelona, Spain, told Healio Rheumatology in an interview. “Overall, the impact to the implementation of a strategy of TNF inhibitor dose reduction on public health budgets could be enormous without any impact on clinical outcomes.”

To assess if a dose-reduction strategy for TNF inhibition could be used without compromising efficacy or inducing unwanted safety outcomes, Gratacós and colleagues conducted a randomized, open-label multicenter clinical trial in a cohort of 126 patients, 113 of whom were included in the main per-protocol subset. Key eligibility criteria included clinical remission for 6 months or more after undergoing treatment with adalimumab (Humira, Abbvie), etanercept (Enbrel, Amgen), infliximab (Remicade, Janssen) or golimumab (Simponi, Janssen).

 
Reduced doses of TNF inhibitor therapy were noninferior to full doses in maintaining low-disease activity after 1 year in a cohort of patients with AS, according to data.
Source: Adobe

According to the researchers, noninferiority in terms of low-disease activity (LDA) at 1 year occurred in 81.3% of 58 patients in the reduced dose arm and 83.8% of 55 patients in the full-dose arm. The researchers reported an adjusted dose difference of 2.5% (95% CI, 16.6 to 11.7).

Safety data showed serious adverse event rates of 3.3% in the reduced-dose arm and 11.3% in the full-dose arm (P = .164).

“Although the noninferiority limit was only demonstrated for LDA, the results were statistically no different and consistent across many variables and TNF inhibitor drugs, confirming the robustness of the data we presented,” Gratacós said. “Serious adverse events and infections were nominally less than one-third in the reduced-dose group as compared to full dose, although not significant. This could suggest that low TNF inhibitor doses might have a better safety profile, but confirmation is needed, since the size and duration of our study were insufficient to draw conclusions.”

Gratacós indicated that these findings could have relevance for clinical practice in terms of both cost and safety. “The direct costs linked to TNF inhibitor treatments is the most limiting factor for extending this treatment to all patients who need it,” he said. “Moreover, it seems to be long-term treatments, so the impact of these treatments on the budget of health public systems is enormous.”

Regarding safety, Gratacós suggested that the low number of severe events in the reduced dose arm may be important, “especially since these are long-term treatments for often-fragile patients,” he said. – by Rob Volansky

Disclosure: Gratacós reports receiving financial support to attend congresses and/or collaborating in work meetings and/or participating in papers financed by: AbbVie, Amgen, Celgene, Janssen, Novartis, and Pfizer Inc.