In the Journals

Switching TNF inhibitors rare, delayed in AS despite inefficacy

Atul Deodhar

TNF-inhibitor switching is rare, and delayed by nearly a full year, among patients with ankylosing spondylitis despite a common lack of efficacy, according to data published in BMC Rheumatology.

“Primary pharmacologic treatment of AS are non-steroidal anti-inflammatory drugs, with biological Disease Modifying Anti-Rheumatic Drugs (bDMARDs) such as tumor necrosis factor inhibitors (TNFi) as a first-line bDMARD option, and the interleukin (IL)-17A inhibitors secukinumab and ixekizumab recommended for patients who have failed TNFi treatment,” Atul Deodhar, MD, MRCP, of the Oregon Health and Science University, and colleagues wrote. “It is not uncommon for patients with AS to experience TNFi therapeutic failure.”

“For example, in a longitudinal, observational study of 249 cases of AS patients treated with TNFi, these agents had been discontinued at 1year in 56 (22.5%) cases,” they added. “Reasons for TNFi discontinuation included lack of efficacy and adverse events in 36.4% and 43.6% of cases, respectively. Interestingly in this study, patients with RA had lower retention rates than patients with AS (65.4% vs 77.5%, respectively), which may reflect fewer options for alternative therapies in AS.”

To evaluate the rates of TNF-inhibitor use and switching, as well as treatment failure and links between failing TNF inhibitors and health-related quality of life, work productivity and activity impairment, Deodhar and colleagues studied data from the Adelphia AS Disease Specific Program. According to the researchers, this program is a large, multinational point-in-tie survey aimed at identifying disease management and impact, as reported by physicians and patients.

 
TNF-inhibitor switching is rare, and delayed by nearly a full year, among patients with AS despite a common lack of efficacy, according to data.
Source: Adobe

For their study, Deodhar and colleagues included data from 2015 to 2016 from 18 countries in North American, South America, Europe, Asia and the Middle East. Their analysis included 640 physicians treating patients with AS and 2,866 adult patients with AS. These participants completed questionnaires regarding demographics, clinical status, TNF-inhibitor history, reasons for switching, quality of life and work productivity and activity. A total of 2,795 included patients had complete treatment data.

TNF-inhibitor treatment was determined to be “failing” if, after 3months or more, physician-rated disease severity had worsened, remained severe or “unstable/deteriorating,” or if physicians were dissatisfied with disease control or did not otherwise consider treatment a success.

According to the researchers, 32.8% of the 2,795 patients with complete treatment data had never received therapy with a TNF inhibitor, while 58.1% were receiving their first TNF inhibitor and 7.2% had ever switched TNF inhibitors. Primary or secondary lack of efficacy were the most common reasons for switching. The mean delay time in switching following a primary lack of efficacy was 11.1months.

In all, 15.4% of patients receiving a TNF inhibitor were currently “failing” treatment. These patients reported poorer health-related quality of life compared with those with treatment success, based on the 5-dimension EuroQoL, Medical Outcomes Study Short-Form Health Survey version 2 mental component summary and physical component summary (P<.001). Among the patients who were failing treatment, 44.5% reported impaired work productivity, compared with 25% among those who were successful. Those for whom TNF inhibitors failed similarly reported impaired activity — 46.4% compared with 25% among those with successful outcomes (P<.001).

“This large multinational real-world study of AS patients demonstrated that lack or loss of efficacy of TNFi is common, yet it appears that patients failing the [first] TNFi (primary lack of efficacy/failure) are not switched to another TNFi for nearly 1 year,” Deodhar and colleagues wrote. “A significant proportion of patients who failed their 1st TNFi did not respond to subsequent TNFi.”

“Failing TNFi therapy is associated with poorer HRQoL, physical activity and work productivity,” they added. “Whether regular monitoring and earlier use of appropriate therapies upon identification of lack of efficacy leads to improvements in symptom control and HRQoL remains to be seen.” – by Jason Laday

Disclosure: Deodhar reports grants or research support from AbbVie, Eli Lilly, GlaxoSmithKline, Janssen, Novartis, Pfizer and UCB Pharma, as well as consulting fees from Eli Lilly, Janssen, Novartis, Pfizer and UCB Pharma. Please see the study for all other authors’ relevant financial disclosures.

Atul Deodhar

TNF-inhibitor switching is rare, and delayed by nearly a full year, among patients with ankylosing spondylitis despite a common lack of efficacy, according to data published in BMC Rheumatology.

“Primary pharmacologic treatment of AS are non-steroidal anti-inflammatory drugs, with biological Disease Modifying Anti-Rheumatic Drugs (bDMARDs) such as tumor necrosis factor inhibitors (TNFi) as a first-line bDMARD option, and the interleukin (IL)-17A inhibitors secukinumab and ixekizumab recommended for patients who have failed TNFi treatment,” Atul Deodhar, MD, MRCP, of the Oregon Health and Science University, and colleagues wrote. “It is not uncommon for patients with AS to experience TNFi therapeutic failure.”

“For example, in a longitudinal, observational study of 249 cases of AS patients treated with TNFi, these agents had been discontinued at 1year in 56 (22.5%) cases,” they added. “Reasons for TNFi discontinuation included lack of efficacy and adverse events in 36.4% and 43.6% of cases, respectively. Interestingly in this study, patients with RA had lower retention rates than patients with AS (65.4% vs 77.5%, respectively), which may reflect fewer options for alternative therapies in AS.”

To evaluate the rates of TNF-inhibitor use and switching, as well as treatment failure and links between failing TNF inhibitors and health-related quality of life, work productivity and activity impairment, Deodhar and colleagues studied data from the Adelphia AS Disease Specific Program. According to the researchers, this program is a large, multinational point-in-tie survey aimed at identifying disease management and impact, as reported by physicians and patients.

 
TNF-inhibitor switching is rare, and delayed by nearly a full year, among patients with AS despite a common lack of efficacy, according to data.
Source: Adobe

For their study, Deodhar and colleagues included data from 2015 to 2016 from 18 countries in North American, South America, Europe, Asia and the Middle East. Their analysis included 640 physicians treating patients with AS and 2,866 adult patients with AS. These participants completed questionnaires regarding demographics, clinical status, TNF-inhibitor history, reasons for switching, quality of life and work productivity and activity. A total of 2,795 included patients had complete treatment data.

TNF-inhibitor treatment was determined to be “failing” if, after 3months or more, physician-rated disease severity had worsened, remained severe or “unstable/deteriorating,” or if physicians were dissatisfied with disease control or did not otherwise consider treatment a success.

According to the researchers, 32.8% of the 2,795 patients with complete treatment data had never received therapy with a TNF inhibitor, while 58.1% were receiving their first TNF inhibitor and 7.2% had ever switched TNF inhibitors. Primary or secondary lack of efficacy were the most common reasons for switching. The mean delay time in switching following a primary lack of efficacy was 11.1months.

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In all, 15.4% of patients receiving a TNF inhibitor were currently “failing” treatment. These patients reported poorer health-related quality of life compared with those with treatment success, based on the 5-dimension EuroQoL, Medical Outcomes Study Short-Form Health Survey version 2 mental component summary and physical component summary (P<.001). Among the patients who were failing treatment, 44.5% reported impaired work productivity, compared with 25% among those who were successful. Those for whom TNF inhibitors failed similarly reported impaired activity — 46.4% compared with 25% among those with successful outcomes (P<.001).

“This large multinational real-world study of AS patients demonstrated that lack or loss of efficacy of TNFi is common, yet it appears that patients failing the [first] TNFi (primary lack of efficacy/failure) are not switched to another TNFi for nearly 1 year,” Deodhar and colleagues wrote. “A significant proportion of patients who failed their 1st TNFi did not respond to subsequent TNFi.”

“Failing TNFi therapy is associated with poorer HRQoL, physical activity and work productivity,” they added. “Whether regular monitoring and earlier use of appropriate therapies upon identification of lack of efficacy leads to improvements in symptom control and HRQoL remains to be seen.” – by Jason Laday

Disclosure: Deodhar reports grants or research support from AbbVie, Eli Lilly, GlaxoSmithKline, Janssen, Novartis, Pfizer and UCB Pharma, as well as consulting fees from Eli Lilly, Janssen, Novartis, Pfizer and UCB Pharma. Please see the study for all other authors’ relevant financial disclosures.