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Long-term use of opioids for musculoskeletal pain incurs major risks
GLASGOW, SCOTLAND – Adverse events ranging from major trauma to osteoporosis to death from any cause occurred at significantly higher rates among people who were prescribed opioids long term for musculoskeletal pain in comparison to those who used a single prescription, in a large retrospective matched cohort study.
The analysis of almost 200,000 patient records from 190 primary care practices held within the U.K. Clinical Practice Research Datalink found that use of opioids to control pain for more than 3 months was associated with an increased risk for major trauma and almost doubled the risk of overdose of nonopioid drugs, compared with short-term use.
The absolute risk for major trauma, which included bone fracture, joint dislocation, ligament or tendon rupture, or head trauma, was 387.4 per 10,000 person-years with long-term opioid use and 269.7 per 10,000 person-years for short-term opioid use, with a hazard ratio (HR) of 1.26 and a 95% confident interval (CI) of 1.20 to 1.33. The absolute risk for overdose with drugs other than opioids was 37.7 and 12.9 per 10,000 person-years, respectively (HR 2.03; 95% CI 1.63-2.53).
Long-term use of opioids led to a significant increase in the risk of accidental poisoning (HR 4.12; 95% CI 1.66-10.19) and becoming newly addicted (HR 2.76; 95% CI 1.76-4.35) in comparison with short-term opioid use. The risk of addiction significantly rose with long-term users of nonopioid drugs (HR 2.16; 95% CI 1.78-2.62), compared with short-term users.
Other risks included an increase in falls (HR 1.20; 95% CI 1.14-1.25) and new cases of osteoporosis (HR 1.65; 95% CI 1.52-1.79), incident depression (HR 1.45; 95% CI 1.37-1.53), new gastric (HR 1.38; 95% CI 1.20-1.60) and nongastric (1.33; 95% CI 1.21-1.45) gastrointestinal bleeding, incident iron deficiency anemia (HR 1.22; 95% CI 1.12-1.33), and death from any cause (HR 1.20; 95% CI 1.12-1.29).
There was no increase in the risk for attempted suicide or self-harm, however, nor in a couple of control outcomes (new cases of eczema or psoriasis) that were tested.
“Long-term users [of opioids] appear to be a very vulnerable group at high risk of experiencing quite a lot of adverse events,” said Dr. John Bedson of Keele (England) University who presented the findings at the British Society for Rheumatology annual conference. “So GPs [general practitioners], naturally, need to be actively managing these patients and ... as this is in the very early stages of prescribing, they need to be assessing the benefit and whether there is a need to carry on taking these medications and stop them if appropriate.”
The use of opioids in patients with musculoskeletal conditions has been increasing in the past 10 years, particularly the use of more potent and long-acting opioids, Dr. Bedson observed. He noted that of all the adults who newly present with musculoskeletal conditions in the United Kingdom – estimated to be 20% of all primary care consulters annually – one in seven will be prescribed an opioid analgesic. In fact, as it was noted during the discussion, U.K. clinicians are now often opting to use opioids over nonsteroidal anti-inflammatory drugs (NSAIDs) to avoid gastrointestinal bleeding.
While there has been some evidence obtained on the risks associated with long-term opioid use in the United States, there has not been data on the risks in a U.K. population. With differing health systems, guidelines, and practices between the two countries, the aim of the retrospective matched cohort study was to compare the adverse event profiles of long- and short-term opioids users over a period of 12 months in a U.K. primary care practice population.
Between 2002 and 2013 there were 98,140 patients with musculoskeletal conditions who had been prescribed opioids and had received two or more further opioid prescriptions within a 90-day period. These were the long-term opioid users; they were matched according to age, gender, and practice to 98,140 short-term opioid users who were patients with musculoskeletal conditions who did not fulfill the criteria for the long-term definition. The median age of patients was 61 years and 41% were male.
Numerous covariates were taken into account, including previous adverse events in the 15 months prior to the start of follow-up, smoking status, alcohol consumption, body mass index, where patients lived and their socioeconomic status, the presence of any comorbidities, and the coprescription of NSAIDs.
Further research into how and why patients on long-term opioids experience more adverse effects needs to be conducted, Dr. Bedson noted, adding that causality had not been found in this study. The next step would be to look at the morphine equivalent doses of the opioids used to see if that had an effect.
But how does the risk compare to long-term use of NSAIDs? Has the preference for opioids been mistaken as being safer?
“The problem is that we have started using these drugs and we don’t know if they work,” Dr. Bedson said. “So we are now at the point of identifying more and more risks, but do they do any good? So I think the jury is still out, and I think GPs have very little else to use at the moment because of the worries over anti-inflammatories, but from an anecdotal point of view I think people are beginning to swing back to using them again.”
Dr. Bedson had no conflicts of interest to disclose.
GLASGOW, SCOTLAND – Adverse events ranging from major trauma to osteoporosis to death from any cause occurred at significantly higher rates among people who were prescribed opioids long term for musculoskeletal pain in comparison to those who used a single prescription, in a large retrospective matched cohort study.
The analysis of almost 200,000 patient records from 190 primary care practices held within the U.K. Clinical Practice Research Datalink found that use of opioids to control pain for more than 3 months was associated with an increased risk for major trauma and almost doubled the risk of overdose of nonopioid drugs, compared with short-term use.
The absolute risk for major trauma, which included bone fracture, joint dislocation, ligament or tendon rupture, or head trauma, was 387.4 per 10,000 person-years with long-term opioid use and 269.7 per 10,000 person-years for short-term opioid use, with a hazard ratio (HR) of 1.26 and a 95% confident interval (CI) of 1.20 to 1.33. The absolute risk for overdose with drugs other than opioids was 37.7 and 12.9 per 10,000 person-years, respectively (HR 2.03; 95% CI 1.63-2.53).
Long-term use of opioids led to a significant increase in the risk of accidental poisoning (HR 4.12; 95% CI 1.66-10.19) and becoming newly addicted (HR 2.76; 95% CI 1.76-4.35) in comparison with short-term opioid use. The risk of addiction significantly rose with long-term users of nonopioid drugs (HR 2.16; 95% CI 1.78-2.62), compared with short-term users.
Other risks included an increase in falls (HR 1.20; 95% CI 1.14-1.25) and new cases of osteoporosis (HR 1.65; 95% CI 1.52-1.79), incident depression (HR 1.45; 95% CI 1.37-1.53), new gastric (HR 1.38; 95% CI 1.20-1.60) and nongastric (1.33; 95% CI 1.21-1.45) gastrointestinal bleeding, incident iron deficiency anemia (HR 1.22; 95% CI 1.12-1.33), and death from any cause (HR 1.20; 95% CI 1.12-1.29).
There was no increase in the risk for attempted suicide or self-harm, however, nor in a couple of control outcomes (new cases of eczema or psoriasis) that were tested.
“Long-term users [of opioids] appear to be a very vulnerable group at high risk of experiencing quite a lot of adverse events,” said Dr. John Bedson of Keele (England) University who presented the findings at the British Society for Rheumatology annual conference. “So GPs [general practitioners], naturally, need to be actively managing these patients and ... as this is in the very early stages of prescribing, they need to be assessing the benefit and whether there is a need to carry on taking these medications and stop them if appropriate.”
The use of opioids in patients with musculoskeletal conditions has been increasing in the past 10 years, particularly the use of more potent and long-acting opioids, Dr. Bedson observed. He noted that of all the adults who newly present with musculoskeletal conditions in the United Kingdom – estimated to be 20% of all primary care consulters annually – one in seven will be prescribed an opioid analgesic. In fact, as it was noted during the discussion, U.K. clinicians are now often opting to use opioids over nonsteroidal anti-inflammatory drugs (NSAIDs) to avoid gastrointestinal bleeding.
While there has been some evidence obtained on the risks associated with long-term opioid use in the United States, there has not been data on the risks in a U.K. population. With differing health systems, guidelines, and practices between the two countries, the aim of the retrospective matched cohort study was to compare the adverse event profiles of long- and short-term opioids users over a period of 12 months in a U.K. primary care practice population.
Between 2002 and 2013 there were 98,140 patients with musculoskeletal conditions who had been prescribed opioids and had received two or more further opioid prescriptions within a 90-day period. These were the long-term opioid users; they were matched according to age, gender, and practice to 98,140 short-term opioid users who were patients with musculoskeletal conditions who did not fulfill the criteria for the long-term definition. The median age of patients was 61 years and 41% were male.
Numerous covariates were taken into account, including previous adverse events in the 15 months prior to the start of follow-up, smoking status, alcohol consumption, body mass index, where patients lived and their socioeconomic status, the presence of any comorbidities, and the coprescription of NSAIDs.
Further research into how and why patients on long-term opioids experience more adverse effects needs to be conducted, Dr. Bedson noted, adding that causality had not been found in this study. The next step would be to look at the morphine equivalent doses of the opioids used to see if that had an effect.
But how does the risk compare to long-term use of NSAIDs? Has the preference for opioids been mistaken as being safer?
“The problem is that we have started using these drugs and we don’t know if they work,” Dr. Bedson said. “So we are now at the point of identifying more and more risks, but do they do any good? So I think the jury is still out, and I think GPs have very little else to use at the moment because of the worries over anti-inflammatories, but from an anecdotal point of view I think people are beginning to swing back to using them again.”
Dr. Bedson had no conflicts of interest to disclose.
GLASGOW, SCOTLAND – Adverse events ranging from major trauma to osteoporosis to death from any cause occurred at significantly higher rates among people who were prescribed opioids long term for musculoskeletal pain in comparison to those who used a single prescription, in a large retrospective matched cohort study.
The analysis of almost 200,000 patient records from 190 primary care practices held within the U.K. Clinical Practice Research Datalink found that use of opioids to control pain for more than 3 months was associated with an increased risk for major trauma and almost doubled the risk of overdose of nonopioid drugs, compared with short-term use.
The absolute risk for major trauma, which included bone fracture, joint dislocation, ligament or tendon rupture, or head trauma, was 387.4 per 10,000 person-years with long-term opioid use and 269.7 per 10,000 person-years for short-term opioid use, with a hazard ratio (HR) of 1.26 and a 95% confident interval (CI) of 1.20 to 1.33. The absolute risk for overdose with drugs other than opioids was 37.7 and 12.9 per 10,000 person-years, respectively (HR 2.03; 95% CI 1.63-2.53).
Long-term use of opioids led to a significant increase in the risk of accidental poisoning (HR 4.12; 95% CI 1.66-10.19) and becoming newly addicted (HR 2.76; 95% CI 1.76-4.35) in comparison with short-term opioid use. The risk of addiction significantly rose with long-term users of nonopioid drugs (HR 2.16; 95% CI 1.78-2.62), compared with short-term users.
Other risks included an increase in falls (HR 1.20; 95% CI 1.14-1.25) and new cases of osteoporosis (HR 1.65; 95% CI 1.52-1.79), incident depression (HR 1.45; 95% CI 1.37-1.53), new gastric (HR 1.38; 95% CI 1.20-1.60) and nongastric (1.33; 95% CI 1.21-1.45) gastrointestinal bleeding, incident iron deficiency anemia (HR 1.22; 95% CI 1.12-1.33), and death from any cause (HR 1.20; 95% CI 1.12-1.29).
There was no increase in the risk for attempted suicide or self-harm, however, nor in a couple of control outcomes (new cases of eczema or psoriasis) that were tested.
“Long-term users [of opioids] appear to be a very vulnerable group at high risk of experiencing quite a lot of adverse events,” said Dr. John Bedson of Keele (England) University who presented the findings at the British Society for Rheumatology annual conference. “So GPs [general practitioners], naturally, need to be actively managing these patients and ... as this is in the very early stages of prescribing, they need to be assessing the benefit and whether there is a need to carry on taking these medications and stop them if appropriate.”
The use of opioids in patients with musculoskeletal conditions has been increasing in the past 10 years, particularly the use of more potent and long-acting opioids, Dr. Bedson observed. He noted that of all the adults who newly present with musculoskeletal conditions in the United Kingdom – estimated to be 20% of all primary care consulters annually – one in seven will be prescribed an opioid analgesic. In fact, as it was noted during the discussion, U.K. clinicians are now often opting to use opioids over nonsteroidal anti-inflammatory drugs (NSAIDs) to avoid gastrointestinal bleeding.
While there has been some evidence obtained on the risks associated with long-term opioid use in the United States, there has not been data on the risks in a U.K. population. With differing health systems, guidelines, and practices between the two countries, the aim of the retrospective matched cohort study was to compare the adverse event profiles of long- and short-term opioids users over a period of 12 months in a U.K. primary care practice population.
Between 2002 and 2013 there were 98,140 patients with musculoskeletal conditions who had been prescribed opioids and had received two or more further opioid prescriptions within a 90-day period. These were the long-term opioid users; they were matched according to age, gender, and practice to 98,140 short-term opioid users who were patients with musculoskeletal conditions who did not fulfill the criteria for the long-term definition. The median age of patients was 61 years and 41% were male.
Numerous covariates were taken into account, including previous adverse events in the 15 months prior to the start of follow-up, smoking status, alcohol consumption, body mass index, where patients lived and their socioeconomic status, the presence of any comorbidities, and the coprescription of NSAIDs.
Further research into how and why patients on long-term opioids experience more adverse effects needs to be conducted, Dr. Bedson noted, adding that causality had not been found in this study. The next step would be to look at the morphine equivalent doses of the opioids used to see if that had an effect.
But how does the risk compare to long-term use of NSAIDs? Has the preference for opioids been mistaken as being safer?
“The problem is that we have started using these drugs and we don’t know if they work,” Dr. Bedson said. “So we are now at the point of identifying more and more risks, but do they do any good? So I think the jury is still out, and I think GPs have very little else to use at the moment because of the worries over anti-inflammatories, but from an anecdotal point of view I think people are beginning to swing back to using them again.”
Dr. Bedson had no conflicts of interest to disclose.
AT RHEUMATOLOGY 2016
Key clinical point: The use of opioids for musculoskeletal pain for more than 3 months is associated with significantly increased risk for many adverse events, compared with single-prescription use.
Major finding: Long-term opioid users were 26% more likely to experience major trauma such as a bone fracture, compared with short-term opioid users.
Data source: Retrospective matched cohort study of almost 200,000 patients using opioids to manage musculoskeletal pain in the United Kingdom.
Disclosures: Dr. Bedson had no conflicts of interest to disclose.
Secukinumab improves patient-reported outcomes in ankylosing spondylitis
GLASGOW, SCOTLAND – Treatment with the anti–interleukin-17A monoclonal antibody secukinumab improved a range of patient-reported outcome measures in a phase III trial of patients with ankylosing spondylitis.
Physical function, quality of life, fatigue, and work productivity were all significantly improved from baseline after 16 weeks of treatment with secukinumab (Cosentyx) versus placebo, and the effects were sustained for up to 1 year.
“PROMs [patient-reported outcome measures] are increasingly seen as the most important outcome measures [in trials] because of their importance to patients,” and they are very closely related to long-term retention and patients’ overall quality of life, Dr. Paul Emery said at the British Society for Rheumatology annual conference.
The new findings come from the MEASURE 2 study, a randomized, double-blind trial of 219 patients treated with one of two doses of secukinumab (150 mg or 75 mg) or placebo. Around 60% of the patient population was male, 95% were white, with a mean age around 42-44 years.
The primary endpoint data from the trial, which was the proportion of patients with at least as 20% improvement in Assessment of Spondyloarthritis International Society (ASAS 20) response criteria at 16 weeks, were published recently (N Engl J Med. 2015;373:2534-48) with the results of the MEASURE 1 study. These showed that a significantly higher percentage of patients treated with the recommended dose of 150 mg, given as a subcutaneous injection every week for the first 3 weeks, then every 4 weeks from week 4, achieved ASAS 20 versus placebo (61% vs. 28%, P less than .001). Effects were sustained, with 62.5%-73.8% of patients still at ASAS 20 at 1 year depending on the type of data analysis performed, and 75% of those who switched from placebo at 16 weeks. The highest response rates were seen in patients who had not received prior anti-TNF therapy (82% vs. 60% for prior therapy at 1 year).
Changes in patients’ general and disease-specific quality of life from baseline to week 16 were predefined secondary endpoints assessed in the MEASURE 2 trial and were determined by the Short-Form (SF) 36 Physical Component Score (PCS) and the AS Quality of Life (ASQoL) questionnaire. Other exploratory endpoints included assessment of these measures at 1 year and the effect of treatment on the SF-36 Mental Component Score (MCS), Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue questionnaire, and the Work Productivity and Activity Impairment-General Health (WPAI-GH) questionnaire.
“One of the things about secukinumab is that you do get very fast responses in the things that matter,” said Dr. Emery of the Leeds (England) Institute of Rheumatic and Musculoskeletal Medicine at the University of Leeds.
Improvement in SF-36 PCS showed improvement as early as week 4, with a mean increase of 6 points from baseline with secukinumab 150 mg versus only 1.9 points for placebo at week 16, and a sustained improvement of 8 points by 1 year. The minimal clinically important difference (MCID) for change in SF-36 is 2.5 points or more. There was not such a clear-cut difference for the SF-36 MCS, but there was a clinically significant improvement of about 4 points at 16 weeks and 6.5 by 1 year.
There was a significant improvement in quality of life versus placebo measured using the ASQoL instrument, with a mean reduction of 4 points for the recommended dose of secukinumab at 16 weeks versus a 1.4 reduction for placebo, and a 5.23 reduction for secukinumab at 1 year. Here the MCID is a change of 1.8 points, Dr. Emery reported.
The MCID for changes in the FACIT-Fatigue score is 4 points or more and this was passed by secukinumab 150 mg at both 16 weeks, with a change of 8 points versus 3.3 points for placebo, and at 1 year, with an increase of 11.5 points for secukinumab.
Work productivity impairment was also improved with active treatment, with mean changes in the WPAI-GH from baseline to week 16 of –16.36 versus –10.22 for placebo, and a sustained reduction of 21.33 at 1 year. Higher scores on this outcome measure mean that work productivity is more severely affected.
Secukinumab was approved for use in ankylosing spondylitis by the European Medicines Agency in October 2015 and more recently by the Food and Drug Administration in January this year. Its availability could be a potential “game changer” for these patients, Dr. Emery suggested, because its mode of action is different from other available therapies, notably the tumor necrosis factor inhibitors. It could become the treatment of choice for AS patients, partially those with enthesitis and psoriasis, at least before drugs that target interleukin (IL)-23 become available that may be better for addressing the spinal component of the disease, he noted during the Q&A that followed his presentation.
Data on radiographic progression will be presented separately, Dr. Emery noted during discussion. He added that secukinumab “certainly works” to reduce radiographic progression, but whether or not it is better than anti-TNF therapy remains to be seen. Because of the mechanism of action on IL-17A, secukinumab could potentially offer an advantage, he said.
“I think it is a game changer because we’ve had such restricted access to therapy previously,” Dr. Emery said. Now having drugs with two different modes of action is a bonus. Deciding which to use first, and in which patients, is the next issue to address.
Novartis supported the study. Dr. Emery has been a paid consultant to AbbVie, Bristol-Myers Squibb, Merck, Novartis, Pfizer, Roche, UCB, Lilly, Samsung, and Sandoz.
GLASGOW, SCOTLAND – Treatment with the anti–interleukin-17A monoclonal antibody secukinumab improved a range of patient-reported outcome measures in a phase III trial of patients with ankylosing spondylitis.
Physical function, quality of life, fatigue, and work productivity were all significantly improved from baseline after 16 weeks of treatment with secukinumab (Cosentyx) versus placebo, and the effects were sustained for up to 1 year.
“PROMs [patient-reported outcome measures] are increasingly seen as the most important outcome measures [in trials] because of their importance to patients,” and they are very closely related to long-term retention and patients’ overall quality of life, Dr. Paul Emery said at the British Society for Rheumatology annual conference.
The new findings come from the MEASURE 2 study, a randomized, double-blind trial of 219 patients treated with one of two doses of secukinumab (150 mg or 75 mg) or placebo. Around 60% of the patient population was male, 95% were white, with a mean age around 42-44 years.
The primary endpoint data from the trial, which was the proportion of patients with at least as 20% improvement in Assessment of Spondyloarthritis International Society (ASAS 20) response criteria at 16 weeks, were published recently (N Engl J Med. 2015;373:2534-48) with the results of the MEASURE 1 study. These showed that a significantly higher percentage of patients treated with the recommended dose of 150 mg, given as a subcutaneous injection every week for the first 3 weeks, then every 4 weeks from week 4, achieved ASAS 20 versus placebo (61% vs. 28%, P less than .001). Effects were sustained, with 62.5%-73.8% of patients still at ASAS 20 at 1 year depending on the type of data analysis performed, and 75% of those who switched from placebo at 16 weeks. The highest response rates were seen in patients who had not received prior anti-TNF therapy (82% vs. 60% for prior therapy at 1 year).
Changes in patients’ general and disease-specific quality of life from baseline to week 16 were predefined secondary endpoints assessed in the MEASURE 2 trial and were determined by the Short-Form (SF) 36 Physical Component Score (PCS) and the AS Quality of Life (ASQoL) questionnaire. Other exploratory endpoints included assessment of these measures at 1 year and the effect of treatment on the SF-36 Mental Component Score (MCS), Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue questionnaire, and the Work Productivity and Activity Impairment-General Health (WPAI-GH) questionnaire.
“One of the things about secukinumab is that you do get very fast responses in the things that matter,” said Dr. Emery of the Leeds (England) Institute of Rheumatic and Musculoskeletal Medicine at the University of Leeds.
Improvement in SF-36 PCS showed improvement as early as week 4, with a mean increase of 6 points from baseline with secukinumab 150 mg versus only 1.9 points for placebo at week 16, and a sustained improvement of 8 points by 1 year. The minimal clinically important difference (MCID) for change in SF-36 is 2.5 points or more. There was not such a clear-cut difference for the SF-36 MCS, but there was a clinically significant improvement of about 4 points at 16 weeks and 6.5 by 1 year.
There was a significant improvement in quality of life versus placebo measured using the ASQoL instrument, with a mean reduction of 4 points for the recommended dose of secukinumab at 16 weeks versus a 1.4 reduction for placebo, and a 5.23 reduction for secukinumab at 1 year. Here the MCID is a change of 1.8 points, Dr. Emery reported.
The MCID for changes in the FACIT-Fatigue score is 4 points or more and this was passed by secukinumab 150 mg at both 16 weeks, with a change of 8 points versus 3.3 points for placebo, and at 1 year, with an increase of 11.5 points for secukinumab.
Work productivity impairment was also improved with active treatment, with mean changes in the WPAI-GH from baseline to week 16 of –16.36 versus –10.22 for placebo, and a sustained reduction of 21.33 at 1 year. Higher scores on this outcome measure mean that work productivity is more severely affected.
Secukinumab was approved for use in ankylosing spondylitis by the European Medicines Agency in October 2015 and more recently by the Food and Drug Administration in January this year. Its availability could be a potential “game changer” for these patients, Dr. Emery suggested, because its mode of action is different from other available therapies, notably the tumor necrosis factor inhibitors. It could become the treatment of choice for AS patients, partially those with enthesitis and psoriasis, at least before drugs that target interleukin (IL)-23 become available that may be better for addressing the spinal component of the disease, he noted during the Q&A that followed his presentation.
Data on radiographic progression will be presented separately, Dr. Emery noted during discussion. He added that secukinumab “certainly works” to reduce radiographic progression, but whether or not it is better than anti-TNF therapy remains to be seen. Because of the mechanism of action on IL-17A, secukinumab could potentially offer an advantage, he said.
“I think it is a game changer because we’ve had such restricted access to therapy previously,” Dr. Emery said. Now having drugs with two different modes of action is a bonus. Deciding which to use first, and in which patients, is the next issue to address.
Novartis supported the study. Dr. Emery has been a paid consultant to AbbVie, Bristol-Myers Squibb, Merck, Novartis, Pfizer, Roche, UCB, Lilly, Samsung, and Sandoz.
GLASGOW, SCOTLAND – Treatment with the anti–interleukin-17A monoclonal antibody secukinumab improved a range of patient-reported outcome measures in a phase III trial of patients with ankylosing spondylitis.
Physical function, quality of life, fatigue, and work productivity were all significantly improved from baseline after 16 weeks of treatment with secukinumab (Cosentyx) versus placebo, and the effects were sustained for up to 1 year.
“PROMs [patient-reported outcome measures] are increasingly seen as the most important outcome measures [in trials] because of their importance to patients,” and they are very closely related to long-term retention and patients’ overall quality of life, Dr. Paul Emery said at the British Society for Rheumatology annual conference.
The new findings come from the MEASURE 2 study, a randomized, double-blind trial of 219 patients treated with one of two doses of secukinumab (150 mg or 75 mg) or placebo. Around 60% of the patient population was male, 95% were white, with a mean age around 42-44 years.
The primary endpoint data from the trial, which was the proportion of patients with at least as 20% improvement in Assessment of Spondyloarthritis International Society (ASAS 20) response criteria at 16 weeks, were published recently (N Engl J Med. 2015;373:2534-48) with the results of the MEASURE 1 study. These showed that a significantly higher percentage of patients treated with the recommended dose of 150 mg, given as a subcutaneous injection every week for the first 3 weeks, then every 4 weeks from week 4, achieved ASAS 20 versus placebo (61% vs. 28%, P less than .001). Effects were sustained, with 62.5%-73.8% of patients still at ASAS 20 at 1 year depending on the type of data analysis performed, and 75% of those who switched from placebo at 16 weeks. The highest response rates were seen in patients who had not received prior anti-TNF therapy (82% vs. 60% for prior therapy at 1 year).
Changes in patients’ general and disease-specific quality of life from baseline to week 16 were predefined secondary endpoints assessed in the MEASURE 2 trial and were determined by the Short-Form (SF) 36 Physical Component Score (PCS) and the AS Quality of Life (ASQoL) questionnaire. Other exploratory endpoints included assessment of these measures at 1 year and the effect of treatment on the SF-36 Mental Component Score (MCS), Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue questionnaire, and the Work Productivity and Activity Impairment-General Health (WPAI-GH) questionnaire.
“One of the things about secukinumab is that you do get very fast responses in the things that matter,” said Dr. Emery of the Leeds (England) Institute of Rheumatic and Musculoskeletal Medicine at the University of Leeds.
Improvement in SF-36 PCS showed improvement as early as week 4, with a mean increase of 6 points from baseline with secukinumab 150 mg versus only 1.9 points for placebo at week 16, and a sustained improvement of 8 points by 1 year. The minimal clinically important difference (MCID) for change in SF-36 is 2.5 points or more. There was not such a clear-cut difference for the SF-36 MCS, but there was a clinically significant improvement of about 4 points at 16 weeks and 6.5 by 1 year.
There was a significant improvement in quality of life versus placebo measured using the ASQoL instrument, with a mean reduction of 4 points for the recommended dose of secukinumab at 16 weeks versus a 1.4 reduction for placebo, and a 5.23 reduction for secukinumab at 1 year. Here the MCID is a change of 1.8 points, Dr. Emery reported.
The MCID for changes in the FACIT-Fatigue score is 4 points or more and this was passed by secukinumab 150 mg at both 16 weeks, with a change of 8 points versus 3.3 points for placebo, and at 1 year, with an increase of 11.5 points for secukinumab.
Work productivity impairment was also improved with active treatment, with mean changes in the WPAI-GH from baseline to week 16 of –16.36 versus –10.22 for placebo, and a sustained reduction of 21.33 at 1 year. Higher scores on this outcome measure mean that work productivity is more severely affected.
Secukinumab was approved for use in ankylosing spondylitis by the European Medicines Agency in October 2015 and more recently by the Food and Drug Administration in January this year. Its availability could be a potential “game changer” for these patients, Dr. Emery suggested, because its mode of action is different from other available therapies, notably the tumor necrosis factor inhibitors. It could become the treatment of choice for AS patients, partially those with enthesitis and psoriasis, at least before drugs that target interleukin (IL)-23 become available that may be better for addressing the spinal component of the disease, he noted during the Q&A that followed his presentation.
Data on radiographic progression will be presented separately, Dr. Emery noted during discussion. He added that secukinumab “certainly works” to reduce radiographic progression, but whether or not it is better than anti-TNF therapy remains to be seen. Because of the mechanism of action on IL-17A, secukinumab could potentially offer an advantage, he said.
“I think it is a game changer because we’ve had such restricted access to therapy previously,” Dr. Emery said. Now having drugs with two different modes of action is a bonus. Deciding which to use first, and in which patients, is the next issue to address.
Novartis supported the study. Dr. Emery has been a paid consultant to AbbVie, Bristol-Myers Squibb, Merck, Novartis, Pfizer, Roche, UCB, Lilly, Samsung, and Sandoz.
AT RHEUMATOLOGY 2016
Key clinical point: Patient-reported outcome measures were improved by secukinumab and sustained at 1 year.
Major finding: Minimal clinically important differences in multiple PROMs were passed, including the SF-36 PCS and ASQoL.
Data source: The MEASURE 2 phase III, randomized, double-blind, placebo-controlled trial of 219 patients with ankylosing spondylitis treated with secukinumab or placebo.
Disclosures: Novartis supported the study. Dr. Emery has been a paid consultant to AbbVie, Bristol-Myers Squibb, Merck, Novartis, Pfizer, Roche, UCB, Lilly, Samsung, and Sandoz.
