Rheumatology meeting: Efficacy, safety of biologics central focus

Abstract

Last November’s American College of Rheumatology (ACR) and Association of Rheumatology Health Professionals (ARHP) Annual Meeting in Washington, DC, covered the latest science, research, and treatment options for the management of rheumatologic conditions. A key focus of the 2012 meeting was the efficacy and safety of various biologics for the treatment of rheumatoid arthritis (RA).A review of key abstracts presented at the meeting will be summarized in this article, and additional information can be accessed at www.rheumatology.org/education/annual/2012_Abstract_Supplement.pdf.■Abatacept and adalimumab resulted in comparable rates of remission in biologic-naive patients with inadequate response to methotrexate.■New data show the novel agent tofacitinib to be safe and efficacious after 2 years.Comparing two biologicsBased on 1-year results from the AMPLE (Abatacept Versus Adalimumab Comparison in Biologic-Naive RA Subjects with Background Methotrexate) trial, Roy Fleischmann, MD, and colleagues reported that use of subcutaneous abatacept (Orencia—Bristol-Myers Squibb) or adalimumab (Humira—Abbott) resulted in comparable rates of remission in biologic-naive patients who had an inadequate response to methotrexate (abstract 1340).AMPLE is the first head-to-head trial to compare the efficacy of two different biologics for the management of RA. In this ongoing, randomized, investigator-blinded, 24-month Phase IIIb study, researchers randomized biologic-naive patients with RA who had an inadequate response to methotrexate to abatacept 125 mg weekly (n = 318) or adalimumab 40 mg biweekly (n = 328). All patients remained on a stable dose of methotrexate throughout the trial. Researchers assessed various remission criteria, including DAS28-CRP (Disease Activity Score 28 Based on C-Reactive Protein), RAPID3 (Routine Assessment of Patient Index Data 3), CDAI (Clinical Disease Activity Index), and SDAI (Simple Disease Activity Index).After 12 months, clinical, functional, and radiographic efficacy, and safety were similar between the two groups. The proportion of patients meeting the various remission criteria for abatacept and adalimumab were 43.3% versus 41.9% for DAS28-CRP < 2.6, 27.2% versus 25.1% for RAPID3 < 1.0, 23.5% versus 24.0% for CDAI < 2.8, and 23.3% versus 24.8% for SDAI < 3.3. Across all assessed remission criteria, 76% to 85% of patients in both treatment arms achieved Health Assessment Questionnaire response at year 1. In addition, 63% to 100% of patients had no radiographic progression, depending on the remission criteria employed.Tofacitinib dataMethotrexate-naive patientsEun Bong Lee, MD, PhD, and colleagues presented results from a Phase III trial that compared the efficacy and safety of tofacitinib 5 mg twice daily (n = 371) and 10 mg twice daily (n = 395) with methotrexate 10–20 mg/wk (n = 186) in methotrexate-naive patients (abstract 2486). Demographic and baseline RA disease characteristics, including radiographic scores such as modified Total Sharp Score (mTSS), were similar among the three groups (mTSS 20.30, 18.85, and 16.51 for tofacitinib 5 mg, tofacitinib 10 mg, and methotrexate, respectively).Mean changes from baseline in mTSS and ACR20, ACR50, and ACR70 (improvement on ACR criteria of 20%, 50%, and 70%, respectively) rates at 6 months were statistically superior for both doses of tofacitinib compared with methotrexate. Secondary radiographic endpoints were also significantly different for tofacitinib compared with methotrexate, with smaller changes in erosion and joint space narrowing scores and greater proportions of patients with no progression from baseline in mTSS scores at month 6. Adverse events were similar among the three groups, but rates of herpes zoster infection were slightly higher in the tofacitinib groups (2.2% for 5-mg dose and 2.5% for 10-mg dose) compared with methotrexate (1.1%).Pharmacists can help with knee OAIn 2012, the American College of Rheumatology highlighted data from Canadian researchers led by Carlo Marra, PharmD, PhD, suggesting that community-based pharmacists could serve as an added resource in identifying patients with knee osteoarthritis (OA).In this randomized, controlled study, 14 pharmacies provided intervention therapy and 18 pharmacies offered usual care as the control group. Marra’s team asked at least two pharmacists at each location to identify and enroll participants 50 years or older who experienced knee pain or stiffness on most days of the last month and fulfilled other criteria, such as a body mass index greater than 25 kg/ m2, no participation in a formal exercise program in the previous 6 months, and difficulty with activities because of knee pain. The 73 patients in the intervention arm received OA screening questionnaires, education, pain medication management, physical therapy exercises, and primary care physician communication. In contrast, the 66 participants in the control group were given an educational pamphlet.The researchers observed a significantly higher quality of OA care as measured by a quality indicator pass rate among patients in the intervention arm than in the control group. At 3 months and at 6 months, participants in the intervention arm saw significantly greater improvement in their overall pain and function scores compared with those receiving usual care.Marra and colleagues concluded that pharmacists can effectively initiate interventions that address the gaps in OA patient care and ultimately improve quality of care, along with patient function, pain, and quality of life. “Collaborative care presents a novel approach in prevent and treating those with knee OA,” he said in the news release.Two-year data for methotrexate-experienced patientsDésirée van der Heijde, MD, PhD and colleagues presented 24-month data from a Phase III study assessing the efficacy and safety of tofacitinib in patients with active RA who had an inadequate response to methotrexate (abstract 1278). The investigators reported that use of tofacitinib 5 mg or 10 mg twice daily over a 24-month period resulted in sustained efficacy as measured by ACR responses, DAS28, and mTSS.Most adverse events that occurred over the 2-year treatment period were mild to moderate and resolved with continued treatment. A total of eight opportunistic infections and four deaths were noted by the investigators; three of the deaths were considered to be related to the study drug. The investigators concluded that patients with RA treated with tofacitinib 5 mg or 10 mg twice daily in addition to stable doses of methotrexate maintained efficacy, including inhibition of structural damage, through 24 months, with no new safety signals emerging over that time period.Benefits of using biologics for RAIn a review of a national recording system over a 16-year period, Leonard Harty, MD, and colleagues found that as use of disease-modifying tumor necrosis factor (TNF) inhibitors increased, the number of patients with RA who required hospitalization for hip or knee surgery decreased significantly (abstract 2540). The researchers analyzed Ireland’s Hospital In-Patient Enquiry System to evaluate the number of hospital inpatient days and musculo-skeletal surgical procedures in patients with RA from 1995 to 2010 and determine if there were any association with use of TNF inhibitors. The study cohort comprised 57,774 records with a female to male ratio of 2:1 and mean age of 66 years.The investigators noted that annual TNF inhibitor prescribing increased by 156% per year, from 2,389 units in 2000 to 116,747 in 2010. In addition, RA inpatient days for any reason declined by approximately 13% per year from about 49,000 per year before 2002 to 31,000 in 2010. The researchers also found a 10% per year decrease in muscular-skeletal procedures from 550 per year before 2002 to 291 in 2010. These results correlated to a 47% reduction in surgical procedures as use of biologics increased over the years.Further analyzing the data, the researchers observed a 44% reduction in hip surgery and a 53% reduction in knee surgery. From this, they concluded that the estimated direct savings attributable to use of TNF inhibitors was approximately €16 million per year (about $20 million).Promising investigational agent for OAThe meeting also featured the presentation of data on the management of osteoarthritis (OA). Researchers discussed promising results for the use of strontium ranelate for knee OA. This agent has a dual mechanism of action in that it increases deposition of new bone osteoblasts and reduces the resorption of bone by osteoclasts.Jean-Yves Reginster, MD, and colleagues presented data from SEKOIA (Strontium Ranelate in Knee Osteoarthritis), a double-blind, placebo-controlled, 3-year study involving 1,683 patients with symptomatic primary knee OA (abstract 1596). Researchers randomized patients to strontium ranelate 1 g/d or 2 g/d or placebo and assessed JSW (joint space width), WOMAC (Western Ontario and McMaster Universities Arthritis Index) scores, knee pain, and adverse events.The investigators observed an association between use of strontium ranelate and less progression of cartilage degradation, with JSW decreasing by 0.23 mm for the 1 g/d and 0.27 mm for the 2 g/d dose groups, compared with a decrease of 0.37 mm for placebo (P < 0.05 for both comparisons). Researchers also noted greater reductions in total WOMAC scores, pain and physical function subscores, and knee pain for patients who received the 2 g/d dose compared with placebo. The percentage of patients reporting an adverse event were similar across the three treatment groups, including the incidence of serious adverse events. Last November’s American College of Rheumatology (ACR) and Association of Rheumatology Health Professionals (ARHP) Annual Meeting in Washington, DC, covered the latest science, research, and treatment options for the management of rheumatologic conditions. A key focus of the 2012 meeting was the efficacy and safety of various biologics for the treatment of rheumatoid arthritis (RA). A review of key abstracts presented at the meeting will be summarized in this article, and additional information can be accessed at www.rheumatology.org/education/annual/2012_Abstract_Supplement.pdf.■Abatacept and adalimumab resulted in comparable rates of remission in biologic-naive patients with inadequate response to methotrexate.■New data show the novel agent tofacitinib to be safe and efficacious after 2 years. ■Abatacept and adalimumab resulted in comparable rates of remission in biologic-naive patients with inadequate response to methotrexate.■New data show the novel agent tofacitinib to be safe and efficacious after 2 years. ■Abatacept and adalimumab resulted in comparable rates of remission in biologic-naive patients with inadequate response to methotrexate.■New data show the novel agent tofacitinib to be safe and efficacious after 2 years. Comparing two biologicsBased on 1-year results from the AMPLE (Abatacept Versus Adalimumab Comparison in Biologic-Naive RA Subjects with Background Methotrexate) trial, Roy Fleischmann, MD, and colleagues reported that use of subcutaneous abatacept (Orencia—Bristol-Myers Squibb) or adalimumab (Humira—Abbott) resulted in comparable rates of remission in biologic-naive patients who had an inadequate response to methotrexate (abstract 1340).AMPLE is the first head-to-head trial to compare the efficacy of two different biologics for the management of RA. In this ongoing, randomized, investigator-blinded, 24-month Phase IIIb study, researchers randomized biologic-naive patients with RA who had an inadequate response to methotrexate to abatacept 125 mg weekly (n = 318) or adalimumab 40 mg biweekly (n = 328). All patients remained on a stable dose of methotrexate throughout the trial. Researchers assessed various remission criteria, including DAS28-CRP (Disease Activity Score 28 Based on C-Reactive Protein), RAPID3 (Routine Assessment of Patient Index Data 3), CDAI (Clinical Disease Activity Index), and SDAI (Simple Disease Activity Index).After 12 months, clinical, functional, and radiographic efficacy, and safety were similar between the two groups. The proportion of patients meeting the various remission criteria for abatacept and adalimumab were 43.3% versus 41.9% for DAS28-CRP < 2.6, 27.2% versus 25.1% for RAPID3 < 1.0, 23.5% versus 24.0% for CDAI < 2.8, and 23.3% versus 24.8% for SDAI < 3.3. Across all assessed remission criteria, 76% to 85% of patients in both treatment arms achieved Health Assessment Questionnaire response at year 1. In addition, 63% to 100% of patients had no radiographic progression, depending on the remission criteria employed. Based on 1-year results from the AMPLE (Abatacept Versus Adalimumab Comparison in Biologic-Naive RA Subjects with Background Methotrexate) trial, Roy Fleischmann, MD, and colleagues reported that use of subcutaneous abatacept (Orencia—Bristol-Myers Squibb) or adalimumab (Humira—Abbott) resulted in comparable rates of remission in biologic-naive patients who had an inadequate response to methotrexate (abstract 1340). AMPLE is the first head-to-head trial to compare the efficacy of two different biologics for the management of RA. In this ongoing, randomized, investigator-blinded, 24-month Phase IIIb study, researchers randomized biologic-naive patients with RA who had an inadequate response to methotrexate to abatacept 125 mg weekly (n = 318) or adalimumab 40 mg biweekly (n = 328). All patients remained on a stable dose of methotrexate throughout the trial. Researchers assessed various remission criteria, including DAS28-CRP (Disease Activity Score 28 Based on C-Reactive Protein), RAPID3 (Routine Assessment of Patient Index Data 3), CDAI (Clinical Disease Activity Index), and SDAI (Simple Disease Activity Index). After 12 months, clinical, functional, and radiographic efficacy, and safety were similar between the two groups. The proportion of patients meeting the various remission criteria for abatacept and adalimumab were 43.3% versus 41.9% for DAS28-CRP < 2.6, 27.2% versus 25.1% for RAPID3 < 1.0, 23.5% versus 24.0% for CDAI < 2.8, and 23.3% versus 24.8% for SDAI < 3.3. Across all assessed remission criteria, 76% to 85% of patients in both treatment arms achieved Health Assessment Questionnaire response at year 1. In addition, 63% to 100% of patients had no radiographic progression, depending on the remission criteria employed. Tofacitinib data Methotrexate-naive patientsEun Bong Lee, MD, PhD, and colleagues presented results from a Phase III trial that compared the efficacy and safety of tofacitinib 5 mg twice daily (n = 371) and 10 mg twice daily (n = 395) with methotrexate 10–20 mg/wk (n = 186) in methotrexate-naive patients (abstract 2486). Demographic and baseline RA disease characteristics, including radiographic scores such as modified Total Sharp Score (mTSS), were similar among the three groups (mTSS 20.30, 18.85, and 16.51 for tofacitinib 5 mg, tofacitinib 10 mg, and methotrexate, respectively).Mean changes from baseline in mTSS and ACR20, ACR50, and ACR70 (improvement on ACR criteria of 20%, 50%, and 70%, respectively) rates at 6 months were statistically superior for both doses of tofacitinib compared with methotrexate. Secondary radiographic endpoints were also significantly different for tofacitinib compared with methotrexate, with smaller changes in erosion and joint space narrowing scores and greater proportions of patients with no progression from baseline in mTSS scores at month 6. Adverse events were similar among the three groups, but rates of herpes zoster infection were slightly higher in the tofacitinib groups (2.2% for 5-mg dose and 2.5% for 10-mg dose) compared with methotrexate (1.1%). Eun Bong Lee, MD, PhD, and colleagues presented results from a Phase III trial that compared the efficacy and safety of tofacitinib 5 mg twice daily (n = 371) and 10 mg twice daily (n = 395) with methotrexate 10–20 mg/wk (n = 186) in methotrexate-naive patients (abstract 2486). Demographic and baseline RA disease characteristics, including radiographic scores such as modified Total Sharp Score (mTSS), were similar among the three groups (mTSS 20.30, 18.85, and 16.51 for tofacitinib 5 mg, tofacitinib 10 mg, and methotrexate, respectively). Mean changes from baseline in mTSS and ACR20, ACR50, and ACR70 (improvement on ACR criteria of 20%, 50%, and 70%, respectively) rates at 6 months were statistically superior for both doses of tofacitinib compared with methotrexate. Secondary radiographic endpoints were also significantly different for tofacitinib compared with methotrexate, with smaller changes in erosion and joint space narrowing scores and greater proportions of patients with no progression from baseline in mTSS scores at month 6. Adverse events were similar among the three groups, but rates of herpes zoster infection were slightly higher in the tofacitinib groups (2.2% for 5-mg dose and 2.5% for 10-mg dose) compared with methotrexate (1.1%). Pharmacists can help with knee OAIn 2012, the American College of Rheumatology highlighted data from Canadian researchers led by Carlo Marra, PharmD, PhD, suggesting that community-based pharmacists could serve as an added resource in identifying patients with knee osteoarthritis (OA).In this randomized, controlled study, 14 pharmacies provided intervention therapy and 18 pharmacies offered usual care as the control group. Marra’s team asked at least two pharmacists at each location to identify and enroll participants 50 years or older who experienced knee pain or stiffness on most days of the last month and fulfilled other criteria, such as a body mass index greater than 25 kg/ m2, no participation in a formal exercise program in the previous 6 months, and difficulty with activities because of knee pain. The 73 patients in the intervention arm received OA screening questionnaires, education, pain medication management, physical therapy exercises, and primary care physician communication. In contrast, the 66 participants in the control group were given an educational pamphlet.The researchers observed a significantly higher quality of OA care as measured by a quality indicator pass rate among patients in the intervention arm than in the control group. At 3 months and at 6 months, participants in the intervention arm saw significantly greater improvement in their overall pain and function scores compared with those receiving usual care.Marra and colleagues concluded that pharmacists can effectively initiate interventions that address the gaps in OA patient care and ultimately improve quality of care, along with patient function, pain, and quality of life. “Collaborative care presents a novel approach in prevent and treating those with knee OA,” he said in the news release. In 2012, the American College of Rheumatology highlighted data from Canadian researchers led by Carlo Marra, PharmD, PhD, suggesting that community-based pharmacists could serve as an added resource in identifying patients with knee osteoarthritis (OA).In this randomized, controlled study, 14 pharmacies provided intervention therapy and 18 pharmacies offered usual care as the control group. Marra’s team asked at least two pharmacists at each location to identify and enroll participants 50 years or older who experienced knee pain or stiffness on most days of the last month and fulfilled other criteria, such as a body mass index greater than 25 kg/ m2, no participation in a formal exercise program in the previous 6 months, and difficulty with activities because of knee pain. The 73 patients in the intervention arm received OA screening questionnaires, education, pain medication management, physical therapy exercises, and primary care physician communication. In contrast, the 66 participants in the control group were given an educational pamphlet.The researchers observed a significantly higher quality of OA care as measured by a quality indicator pass rate among patients in the intervention arm than in the control group. At 3 months and at 6 months, participants in the intervention arm saw significantly greater improvement in their overall pain and function scores compared with those receiving usual care.Marra and colleagues concluded that pharmacists can effectively initiate interventions that address the gaps in OA patient care and ultimately improve quality of care, along with patient function, pain, and quality of life. “Collaborative care presents a novel approach in prevent and treating those with knee OA,” he said in the news release. In 2012, the American College of Rheumatology highlighted data from Canadian researchers led by Carlo Marra, PharmD, PhD, suggesting that community-based pharmacists could serve as an added resource in identifying patients with knee osteoarthritis (OA). In this randomized, controlled study, 14 pharmacies provided intervention therapy and 18 pharmacies offered usual care as the control group. Marra’s team asked at least two pharmacists at each location to identify and enroll participants 50 years or older who experienced knee pain or stiffness on most days of the last month and fulfilled other criteria, such as a body mass index greater than 25 kg/ m2, no participation in a formal exercise program in the previous 6 months, and difficulty with activities because of knee pain. The 73 patients in the intervention arm received OA screening questionnaires, education, pain medication management, physical therapy exercises, and primary care physician communication. In contrast, the 66 participants in the control group were given an educational pamphlet. The researchers observed a significantly higher quality of OA care as measured by a quality indicator pass rate among patients in the intervention arm than in the control group. At 3 months and at 6 months, participants in the intervention arm saw significantly greater improvement in their overall pain and function scores compared with those receiving usual care. Marra and colleagues concluded that pharmacists can effectively initiate interventions that address the gaps in OA patient care and ultimately improve quality of care, along with patient function, pain, and quality of life. “Collaborative care presents a novel approach in prevent and treating those with knee OA,” he said in the news release. Two-year data for methotrexate-experienced patientsDésirée van der Heijde, MD, PhD and colleagues presented 24-month data from a Phase III study assessing the efficacy and safety of tofacitinib in patients with active RA who had an inadequate response to methotrexate (abstract 1278). The investigators reported that use of tofacitinib 5 mg or 10 mg twice daily over a 24-month period resulted in sustained efficacy as measured by ACR responses, DAS28, and mTSS.Most adverse events that occurred over the 2-year treatment period were mild to moderate and resolved with continued treatment. A total of eight opportunistic infections and four deaths were noted by the investigators; three of the deaths were considered to be related to the study drug. The investigators concluded that patients with RA treated with tofacitinib 5 mg or 10 mg twice daily in addition to stable doses of methotrexate maintained efficacy, including inhibition of structural damage, through 24 months, with no new safety signals emerging over that time period. Désirée van der Heijde, MD, PhD and colleagues presented 24-month data from a Phase III study assessing the efficacy and safety of tofacitinib in patients with active RA who had an inadequate response to methotrexate (abstract 1278). The investigators reported that use of tofacitinib 5 mg or 10 mg twice daily over a 24-month period resulted in sustained efficacy as measured by ACR responses, DAS28, and mTSS. Most adverse events that occurred over the 2-year treatment period were mild to moderate and resolved with continued treatment. A total of eight opportunistic infections and four deaths were noted by the investigators; three of the deaths were considered to be related to the study drug. The investigators concluded that patients with RA treated with tofacitinib 5 mg or 10 mg twice daily in addition to stable doses of methotrexate maintained efficacy, including inhibition of structural damage, through 24 months, with no new safety signals emerging over that time period. Benefits of using biologics for RAIn a review of a national recording system over a 16-year period, Leonard Harty, MD, and colleagues found that as use of disease-modifying tumor necrosis factor (TNF) inhibitors increased, the number of patients with RA who required hospitalization for hip or knee surgery decreased significantly (abstract 2540). The researchers analyzed Ireland’s Hospital In-Patient Enquiry System to evaluate the number of hospital inpatient days and musculo-skeletal surgical procedures in patients with RA from 1995 to 2010 and determine if there were any association with use of TNF inhibitors. The study cohort comprised 57,774 records with a female to male ratio of 2:1 and mean age of 66 years.The investigators noted that annual TNF inhibitor prescribing increased by 156% per year, from 2,389 units in 2000 to 116,747 in 2010. In addition, RA inpatient days for any reason declined by approximately 13% per year from about 49,000 per year before 2002 to 31,000 in 2010. The researchers also found a 10% per year decrease in muscular-skeletal procedures from 550 per year before 2002 to 291 in 2010. These results correlated to a 47% reduction in surgical procedures as use of biologics increased over the years.Further analyzing the data, the researchers observed a 44% reduction in hip surgery and a 53% reduction in knee surgery. From this, they concluded that the estimated direct savings attributable to use of TNF inhibitors was approximately €16 million per year (about $20 million). In a review of a national recording system over a 16-year period, Leonard Harty, MD, and colleagues found that as use of disease-modifying tumor necrosis factor (TNF) inhibitors increased, the number of patients with RA who required hospitalization for hip or knee surgery decreased significantly (abstract 2540). The researchers analyzed Ireland’s Hospital In-Patient Enquiry System to evaluate the number of hospital inpatient days and musculo-skeletal surgical procedures in patients with RA from 1995 to 2010 and determine if there were any association with use of TNF inhibitors. The study cohort comprised 57,774 records with a female to male ratio of 2:1 and mean age of 66 years. The investigators noted that annual TNF inhibitor prescribing increased by 156% per year, from 2,389 units in 2000 to 116,747 in 2010. In addition, RA inpatient days for any reason declined by approximately 13% per year from about 49,000 per year before 2002 to 31,000 in 2010. The researchers also found a 10% per year decrease in muscular-skeletal procedures from 550 per year before 2002 to 291 in 2010. These results correlated to a 47% reduction in surgical procedures as use of biologics increased over the years. Further analyzing the data, the researchers observed a 44% reduction in hip surgery and a 53% reduction in knee surgery. From this, they concluded that the estimated direct savings attributable to use of TNF inhibitors was approximately €16 million per year (about $20 million). Promising investigational agent for OAThe meeting also featured the presentation of data on the management of osteoarthritis (OA). Researchers discussed promising results for the use of strontium ranelate for knee OA. This agent has a dual mechanism of action in that it increases deposition of new bone osteoblasts and reduces the resorption of bone by osteoclasts.Jean-Yves Reginster, MD, and colleagues presented data from SEKOIA (Strontium Ranelate in Knee Osteoarthritis), a double-blind, placebo-controlled, 3-year study involving 1,683 patients with symptomatic primary knee OA (abstract 1596). Researchers randomized patients to strontium ranelate 1 g/d or 2 g/d or placebo and assessed JSW (joint space width), WOMAC (Western Ontario and McMaster Universities Arthritis Index) scores, knee pain, and adverse events.The investigators observed an association between use of strontium ranelate and less progression of cartilage degradation, with JSW decreasing by 0.23 mm for the 1 g/d and 0.27 mm for the 2 g/d dose groups, compared with a decrease of 0.37 mm for placebo (P < 0.05 for both comparisons). Researchers also noted greater reductions in total WOMAC scores, pain and physical function subscores, and knee pain for patients who received the 2 g/d dose compared with placebo. The percentage of patients reporting an adverse event were similar across the three treatment groups, including the incidence of serious adverse events. The meeting also featured the presentation of data on the management of osteoarthritis (OA). Researchers discussed promising results for the use of strontium ranelate for knee OA. This agent has a dual mechanism of action in that it increases deposition of new bone osteoblasts and reduces the resorption of bone by osteoclasts. Jean-Yves Reginster, MD, and colleagues presented data from SEKOIA (Strontium Ranelate in Knee Osteoarthritis), a double-blind, placebo-controlled, 3-year study involving 1,683 patients with symptomatic primary knee OA (abstract 1596). Researchers randomized patients to strontium ranelate 1 g/d or 2 g/d or placebo and assessed JSW (joint space width), WOMAC (Western Ontario and McMaster Universities Arthritis Index) scores, knee pain, and adverse events. The investigators observed an association between use of strontium ranelate and less progression of cartilage degradation, with JSW decreasing by 0.23 mm for the 1 g/d and 0.27 mm for the 2 g/d dose groups, compared with a decrease of 0.37 mm for placebo (P < 0.05 for both comparisons). Researchers also noted greater reductions in total WOMAC scores, pain and physical function subscores, and knee pain for patients who received the 2 g/d dose compared with placebo. The percentage of patients reporting an adverse event were similar across the three treatment groups, including the incidence of serious adverse events.