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MAUI, HAWAII – Osteoarthritis therapy remains a barren landscape where conventional medicine has so little to offer that many affected patients eagerly embrace unproven Internet claims for costly out-of-pocket intra-articular injections of platelet-rich plasma, oxygen ozone, and mesenchymal stem cells, Eric M. Ruderman, MD, said at the 2020 Rheumatology Winter Clinical Symposium.
He presented a whirlwind review of the evidence – or lack thereof – for a wide range of contemporary OA therapies, ranging from acupuncture to cupping, lateral wedge insoles, various substances for intra-articular injection, radiofrequency therapy, medical leeches, and several widely ballyhooed medications that are well along in the developmental pipeline but whose placebo-subtracted efficacy is actually quite modest.
“I’ve shown you the evidence, such as it is – it’s not very much. The question is, have we really moved the needle in this disease in the last 30 years? The answer is I’m not so sure we have,” concluded Dr. Ruderman, professor of medicine and associate chief for clinical affairs in the division of rheumatology at Northwestern University, Chicago.
Several audience members were less restrained in their assessments.
“You have not moved the needle in osteoarthritis,” stated orthopedic surgeon William Bugbee, MD, chief of joint reconstruction at the Scripps Clinic in La Jolla, Calif., adding that he’s not much impressed by the long-term impact of intra-articular injections, be they of glucocorticoid, hyaluronic acid, or anything else being put into osteoarthritic joints.
“To me, and to most orthopedic surgeons, an injection is a handshake. It’s like: ‘How do you do? Let’s get to know each other.’ But you know where this interaction is going – it’s going to end up in surgery. But that’s okay. Surgery is great. Let’s face it: It’s the only disease-modifying treatment for OA,” Dr. Bugbee declared.
Roy Fleischmann, MD, rose from the audience to assert that “the biggest need in rheumatology right now is a medication for OA that actually works and is actually disease modifying.”
That’s not going to happen until clinical trialists and the pharmaceutical industry learn how to subgroup OA and separate inflammatory OA from noninflammatory OA. Lumping the two together tends to wash out any strong efficacy signal an investigational agent might have, added Dr. Fleischmann, a rheumatologist at the University of Texas and medical director of the Metroplex Clinical Research Center, both in Dallas.
Dr. Ruderman noted that his own analysis of the contemporary evidence base for OA pharmacotherapies reached conclusions generally similar to those contained in the new American College of Rheumatology/Arthritis Foundation “Guideline for the Management of Osteoarthritis of the Hand, Hip, and Knee”. The list of pharmacotherapies that were strongly recommended in the guidelines was slim and rather tired: oral NSAIDs, intra-articular glucocorticoid injections, and – for knee OA only – topical NSAIDs. The strength of those favorable recommendations was based more upon solid evidence of safety rather than impressive efficacy, in his view. And the guidelines’ list of therapies whose use was strongly discouraged was much longer.
A factor in the flimsy evidence base for OA treatment is the strikingly large across-the-board placebo effect. This was nicely captured in a meta-analysis of 215 randomized, controlled trials of various therapies totaling more than 41,000 participants. Drilling down into the data, the British and Chinese investigators concluded that on average 75% of the overall treatment effect seen in the trials was caused by the placebo effect and only 25% represented a treatment-specific effect. The “winner” was intra-articular glucocorticoid, where the placebo effect was a mere 47%.
In the OA pipeline
“There’s a lot of interest in DMOADs – disease-modifying osteoarthritis drugs – but not a lot of success so far,” Dr. Ruderman observed.
Case in point: intra-articular sprifermin, a recombinant human fibroblast growth factor 18. In a 549-patient, multicenter, dose-ranging study, the two highest doses achieved a modest yet statistically significant advantage over placebo in total femorotibial joint cartilage thickness on MRI at 2 years. However, the investigators added that the result was of “uncertain clinical importance,” given the lack of a difference from baseline in total Western Ontario and McMaster Universities OA Index score.
“I’m not sure this is going anywhere,” Dr. Ruderman commented.
Tanezumab, a novel subcutaneously injected monoclonal antibody directed against nerve growth factor, has drawn a lot of attention. In an initial multicenter, phase 3, randomized trial it showed what Dr. Ruderman termed “some modest benefit” on pain and function.
“Very much like everything else in OA, you see a huge placebo effect buried in there,” according to the rheumatologist.
This modest clinical benefit was accompanied by a safety signal at the higher 5-mg dose of tanezumab. Moreover, a second phase 3 trial, this one conducted in nearly 3,000 OA patients and presented at the 2019 annual meeting of the American College of Rheumatology, also raised significant safety concerns at the higher dose. And while the 2.5-mg dose was safer, it was disappointingly no more effective in terms of improvement in pain and function scores than diclofenac at 75 mg twice daily, Dr. Ruderman noted.
Dr. Fleischmann predicted that, given the enormous unmet need for new OA treatments, tanezumab at 2.5 mg will win regulatory approval, but it will be a costly niche drug reserved for the challenging subset of patients who can’t take an NSAID and are poor surgical candidates. (On March 2, 2020, Eli Lilly announced that the Food and Drug Administration had accepted its Biologics License Application for tanezumab for the treatment of chronic pain caused by moderate to severe OA.)
Intra-articular FX006, a microsphere-based, extended-release formulation of triamcinolone, outperformed conventional triamcinolone in a phase 3 clinical trial. However, the placebo-subtracted improvement in pain was modest.
“There’s some marginal benefit here, but over time I’m not sure this adds much to just straight-up triamcinolone,” Dr. Ruderman opined.
Welcome to the wild, wild West
Patients with knee OA ask Dr. Ruderman all the time about the intra-articular injections of platelet-rich plasma (PRP) or mesenchymal stem cells they’ve seen touted on the Internet. As an evidence-based physician, he’s not a fan. A meta-analysis of 14 controlled trials of PRP, none double blind, showed some benefit in terms of pain and function at 3, 6, and 12 months, with little risk of adverse events. However, PRP is being marketed with a hype and claimed efficacy out of all proportion to the actual evidence.
“It’s the wild, wild West out there,” the rheumatologist warned.
He cited a study involving a scripted survey of 179 U.S. clinics offering PRP. The mean price quoted for a unilateral knee injection in a hypothetical 52-year-old man with knee OA was $714, and it’s a cash business, since insurance companies won’t cover PRP. Out of 84 centers that were willing to share their claimed efficacy, 10 quoted 90%-100% rates of good results or symptomatic improvement, 27 claimed 80%-90% efficacy, and 29 quoted figures of 70%-80%, all of which are well above the success rates achieved in the flawed clinical trials.
As for mesenchymal stem cells, “if PRP is the wild, wild West, this is the surface of Mars,” Dr. Ruderman quipped.
These stem cell injections are neither FDA regulated nor approved. There are no barriers to setting up a mesenchymal stem cell injection center, and the number of such centers is skyrocketing. Anybody can set up a center, and there’s essentially no oversight.
“The evidence in this area is really terrible,” the rheumatologist said. He pointed to a meta-analysis of five trials, only two of which were rated by the researchers as having a low risk of bias. The conclusion: There was limited evidence of short-term benefit in pain and function, but no evidence of cartilage repair, which is the chief claimed benefit.
The same group of investigators who queried the PRP clinics also successfully contacted 273 of the proliferating U.S. centers offering direct-to-consumer mesenchymal stem cell therapy. The mean price quoted for a unilateral knee injection was a whopping $5,156, which – like PRP – isn’t covered by insurance. At the 36 clinics responding to a request for their efficacy rates, the mean claim was good results or symptomatic improvement in 82% of treated patients.
Dr. Bugbee didn’t endorse this intervention, which is increasingly popular among his fellow orthopedic surgeons.
“The regulatory pathway drives this. Mesenchymal stem cells are categorized as a minimally manipulated tissue, so the regulatory pathway is easy,” explained Dr. Bugbee. “I talk 9 out of 10 patients out of it because there’s no evidence of disease modification.”
On a brighter note
Radiofrequency ablation and neuromodulation procedures for treatment of symptomatic knee OA make no pretense of being disease modifying, but a new systematic review of 33 published studies deemed of moderate or high methodological quality totaling 1,512 patients documented improved pain, function, and disease-specific quality of life for 3-12 months with minimal complications.
Most of these procedures target the genicular nerve, the sensory nerve that innervates the knee.
“There’s some value here to this,” Dr. Ruderman said. “Our pain folks are actually pretty interested in this. At our center, they’re using this for patients with persistent knee pain after knee replacement, with some success. It’s not an unreasonable approach.”
As part of his examination of the evidence base for OA treatment, Dr. Ruderman looked into an intervention he wasn’t familiar with: acupuncture. He was pleasantly surprised.
“There’s quite a bit of data. There is decent evidence that acupuncture has significant benefit, at least for pain, and is certainly without significant side effects,” according to the rheumatologist.
He cited a review of a dozen systematic reviews of randomized, controlled trials of acupuncture for OA. The Chinese investigators rated the overall quality of the evidence as moderate to low, but with some studies being rated high quality. “That’s not as bad as some of the other stuff I looked at,” Dr. Ruderman said.
Acupuncture was found to be 2.4 times more effective than Western medicine for short-term pain relief, and 4.1 times better in terms of total efficacy, with a lower risk of adverse events than with Western medicine.
Dr. Ruderman reported serving as a consultant for and/or receiving research grants from more than a half-dozen pharmaceutical companies.
MAUI, HAWAII – Osteoarthritis therapy remains a barren landscape where conventional medicine has so little to offer that many affected patients eagerly embrace unproven Internet claims for costly out-of-pocket intra-articular injections of platelet-rich plasma, oxygen ozone, and mesenchymal stem cells, Eric M. Ruderman, MD, said at the 2020 Rheumatology Winter Clinical Symposium.
He presented a whirlwind review of the evidence – or lack thereof – for a wide range of contemporary OA therapies, ranging from acupuncture to cupping, lateral wedge insoles, various substances for intra-articular injection, radiofrequency therapy, medical leeches, and several widely ballyhooed medications that are well along in the developmental pipeline but whose placebo-subtracted efficacy is actually quite modest.
“I’ve shown you the evidence, such as it is – it’s not very much. The question is, have we really moved the needle in this disease in the last 30 years? The answer is I’m not so sure we have,” concluded Dr. Ruderman, professor of medicine and associate chief for clinical affairs in the division of rheumatology at Northwestern University, Chicago.
Several audience members were less restrained in their assessments.
“You have not moved the needle in osteoarthritis,” stated orthopedic surgeon William Bugbee, MD, chief of joint reconstruction at the Scripps Clinic in La Jolla, Calif., adding that he’s not much impressed by the long-term impact of intra-articular injections, be they of glucocorticoid, hyaluronic acid, or anything else being put into osteoarthritic joints.
“To me, and to most orthopedic surgeons, an injection is a handshake. It’s like: ‘How do you do? Let’s get to know each other.’ But you know where this interaction is going – it’s going to end up in surgery. But that’s okay. Surgery is great. Let’s face it: It’s the only disease-modifying treatment for OA,” Dr. Bugbee declared.
Roy Fleischmann, MD, rose from the audience to assert that “the biggest need in rheumatology right now is a medication for OA that actually works and is actually disease modifying.”
That’s not going to happen until clinical trialists and the pharmaceutical industry learn how to subgroup OA and separate inflammatory OA from noninflammatory OA. Lumping the two together tends to wash out any strong efficacy signal an investigational agent might have, added Dr. Fleischmann, a rheumatologist at the University of Texas and medical director of the Metroplex Clinical Research Center, both in Dallas.
Dr. Ruderman noted that his own analysis of the contemporary evidence base for OA pharmacotherapies reached conclusions generally similar to those contained in the new American College of Rheumatology/Arthritis Foundation “Guideline for the Management of Osteoarthritis of the Hand, Hip, and Knee”. The list of pharmacotherapies that were strongly recommended in the guidelines was slim and rather tired: oral NSAIDs, intra-articular glucocorticoid injections, and – for knee OA only – topical NSAIDs. The strength of those favorable recommendations was based more upon solid evidence of safety rather than impressive efficacy, in his view. And the guidelines’ list of therapies whose use was strongly discouraged was much longer.
A factor in the flimsy evidence base for OA treatment is the strikingly large across-the-board placebo effect. This was nicely captured in a meta-analysis of 215 randomized, controlled trials of various therapies totaling more than 41,000 participants. Drilling down into the data, the British and Chinese investigators concluded that on average 75% of the overall treatment effect seen in the trials was caused by the placebo effect and only 25% represented a treatment-specific effect. The “winner” was intra-articular glucocorticoid, where the placebo effect was a mere 47%.
In the OA pipeline
“There’s a lot of interest in DMOADs – disease-modifying osteoarthritis drugs – but not a lot of success so far,” Dr. Ruderman observed.
Case in point: intra-articular sprifermin, a recombinant human fibroblast growth factor 18. In a 549-patient, multicenter, dose-ranging study, the two highest doses achieved a modest yet statistically significant advantage over placebo in total femorotibial joint cartilage thickness on MRI at 2 years. However, the investigators added that the result was of “uncertain clinical importance,” given the lack of a difference from baseline in total Western Ontario and McMaster Universities OA Index score.
“I’m not sure this is going anywhere,” Dr. Ruderman commented.
Tanezumab, a novel subcutaneously injected monoclonal antibody directed against nerve growth factor, has drawn a lot of attention. In an initial multicenter, phase 3, randomized trial it showed what Dr. Ruderman termed “some modest benefit” on pain and function.
“Very much like everything else in OA, you see a huge placebo effect buried in there,” according to the rheumatologist.
This modest clinical benefit was accompanied by a safety signal at the higher 5-mg dose of tanezumab. Moreover, a second phase 3 trial, this one conducted in nearly 3,000 OA patients and presented at the 2019 annual meeting of the American College of Rheumatology, also raised significant safety concerns at the higher dose. And while the 2.5-mg dose was safer, it was disappointingly no more effective in terms of improvement in pain and function scores than diclofenac at 75 mg twice daily, Dr. Ruderman noted.
Dr. Fleischmann predicted that, given the enormous unmet need for new OA treatments, tanezumab at 2.5 mg will win regulatory approval, but it will be a costly niche drug reserved for the challenging subset of patients who can’t take an NSAID and are poor surgical candidates. (On March 2, 2020, Eli Lilly announced that the Food and Drug Administration had accepted its Biologics License Application for tanezumab for the treatment of chronic pain caused by moderate to severe OA.)
Intra-articular FX006, a microsphere-based, extended-release formulation of triamcinolone, outperformed conventional triamcinolone in a phase 3 clinical trial. However, the placebo-subtracted improvement in pain was modest.
“There’s some marginal benefit here, but over time I’m not sure this adds much to just straight-up triamcinolone,” Dr. Ruderman opined.
Welcome to the wild, wild West
Patients with knee OA ask Dr. Ruderman all the time about the intra-articular injections of platelet-rich plasma (PRP) or mesenchymal stem cells they’ve seen touted on the Internet. As an evidence-based physician, he’s not a fan. A meta-analysis of 14 controlled trials of PRP, none double blind, showed some benefit in terms of pain and function at 3, 6, and 12 months, with little risk of adverse events. However, PRP is being marketed with a hype and claimed efficacy out of all proportion to the actual evidence.
“It’s the wild, wild West out there,” the rheumatologist warned.
He cited a study involving a scripted survey of 179 U.S. clinics offering PRP. The mean price quoted for a unilateral knee injection in a hypothetical 52-year-old man with knee OA was $714, and it’s a cash business, since insurance companies won’t cover PRP. Out of 84 centers that were willing to share their claimed efficacy, 10 quoted 90%-100% rates of good results or symptomatic improvement, 27 claimed 80%-90% efficacy, and 29 quoted figures of 70%-80%, all of which are well above the success rates achieved in the flawed clinical trials.
As for mesenchymal stem cells, “if PRP is the wild, wild West, this is the surface of Mars,” Dr. Ruderman quipped.
These stem cell injections are neither FDA regulated nor approved. There are no barriers to setting up a mesenchymal stem cell injection center, and the number of such centers is skyrocketing. Anybody can set up a center, and there’s essentially no oversight.
“The evidence in this area is really terrible,” the rheumatologist said. He pointed to a meta-analysis of five trials, only two of which were rated by the researchers as having a low risk of bias. The conclusion: There was limited evidence of short-term benefit in pain and function, but no evidence of cartilage repair, which is the chief claimed benefit.
The same group of investigators who queried the PRP clinics also successfully contacted 273 of the proliferating U.S. centers offering direct-to-consumer mesenchymal stem cell therapy. The mean price quoted for a unilateral knee injection was a whopping $5,156, which – like PRP – isn’t covered by insurance. At the 36 clinics responding to a request for their efficacy rates, the mean claim was good results or symptomatic improvement in 82% of treated patients.
Dr. Bugbee didn’t endorse this intervention, which is increasingly popular among his fellow orthopedic surgeons.
“The regulatory pathway drives this. Mesenchymal stem cells are categorized as a minimally manipulated tissue, so the regulatory pathway is easy,” explained Dr. Bugbee. “I talk 9 out of 10 patients out of it because there’s no evidence of disease modification.”
On a brighter note
Radiofrequency ablation and neuromodulation procedures for treatment of symptomatic knee OA make no pretense of being disease modifying, but a new systematic review of 33 published studies deemed of moderate or high methodological quality totaling 1,512 patients documented improved pain, function, and disease-specific quality of life for 3-12 months with minimal complications.
Most of these procedures target the genicular nerve, the sensory nerve that innervates the knee.
“There’s some value here to this,” Dr. Ruderman said. “Our pain folks are actually pretty interested in this. At our center, they’re using this for patients with persistent knee pain after knee replacement, with some success. It’s not an unreasonable approach.”
As part of his examination of the evidence base for OA treatment, Dr. Ruderman looked into an intervention he wasn’t familiar with: acupuncture. He was pleasantly surprised.
“There’s quite a bit of data. There is decent evidence that acupuncture has significant benefit, at least for pain, and is certainly without significant side effects,” according to the rheumatologist.
He cited a review of a dozen systematic reviews of randomized, controlled trials of acupuncture for OA. The Chinese investigators rated the overall quality of the evidence as moderate to low, but with some studies being rated high quality. “That’s not as bad as some of the other stuff I looked at,” Dr. Ruderman said.
Acupuncture was found to be 2.4 times more effective than Western medicine for short-term pain relief, and 4.1 times better in terms of total efficacy, with a lower risk of adverse events than with Western medicine.
Dr. Ruderman reported serving as a consultant for and/or receiving research grants from more than a half-dozen pharmaceutical companies.
MAUI, HAWAII – Osteoarthritis therapy remains a barren landscape where conventional medicine has so little to offer that many affected patients eagerly embrace unproven Internet claims for costly out-of-pocket intra-articular injections of platelet-rich plasma, oxygen ozone, and mesenchymal stem cells, Eric M. Ruderman, MD, said at the 2020 Rheumatology Winter Clinical Symposium.
He presented a whirlwind review of the evidence – or lack thereof – for a wide range of contemporary OA therapies, ranging from acupuncture to cupping, lateral wedge insoles, various substances for intra-articular injection, radiofrequency therapy, medical leeches, and several widely ballyhooed medications that are well along in the developmental pipeline but whose placebo-subtracted efficacy is actually quite modest.
“I’ve shown you the evidence, such as it is – it’s not very much. The question is, have we really moved the needle in this disease in the last 30 years? The answer is I’m not so sure we have,” concluded Dr. Ruderman, professor of medicine and associate chief for clinical affairs in the division of rheumatology at Northwestern University, Chicago.
Several audience members were less restrained in their assessments.
“You have not moved the needle in osteoarthritis,” stated orthopedic surgeon William Bugbee, MD, chief of joint reconstruction at the Scripps Clinic in La Jolla, Calif., adding that he’s not much impressed by the long-term impact of intra-articular injections, be they of glucocorticoid, hyaluronic acid, or anything else being put into osteoarthritic joints.
“To me, and to most orthopedic surgeons, an injection is a handshake. It’s like: ‘How do you do? Let’s get to know each other.’ But you know where this interaction is going – it’s going to end up in surgery. But that’s okay. Surgery is great. Let’s face it: It’s the only disease-modifying treatment for OA,” Dr. Bugbee declared.
Roy Fleischmann, MD, rose from the audience to assert that “the biggest need in rheumatology right now is a medication for OA that actually works and is actually disease modifying.”
That’s not going to happen until clinical trialists and the pharmaceutical industry learn how to subgroup OA and separate inflammatory OA from noninflammatory OA. Lumping the two together tends to wash out any strong efficacy signal an investigational agent might have, added Dr. Fleischmann, a rheumatologist at the University of Texas and medical director of the Metroplex Clinical Research Center, both in Dallas.
Dr. Ruderman noted that his own analysis of the contemporary evidence base for OA pharmacotherapies reached conclusions generally similar to those contained in the new American College of Rheumatology/Arthritis Foundation “Guideline for the Management of Osteoarthritis of the Hand, Hip, and Knee”. The list of pharmacotherapies that were strongly recommended in the guidelines was slim and rather tired: oral NSAIDs, intra-articular glucocorticoid injections, and – for knee OA only – topical NSAIDs. The strength of those favorable recommendations was based more upon solid evidence of safety rather than impressive efficacy, in his view. And the guidelines’ list of therapies whose use was strongly discouraged was much longer.
A factor in the flimsy evidence base for OA treatment is the strikingly large across-the-board placebo effect. This was nicely captured in a meta-analysis of 215 randomized, controlled trials of various therapies totaling more than 41,000 participants. Drilling down into the data, the British and Chinese investigators concluded that on average 75% of the overall treatment effect seen in the trials was caused by the placebo effect and only 25% represented a treatment-specific effect. The “winner” was intra-articular glucocorticoid, where the placebo effect was a mere 47%.
In the OA pipeline
“There’s a lot of interest in DMOADs – disease-modifying osteoarthritis drugs – but not a lot of success so far,” Dr. Ruderman observed.
Case in point: intra-articular sprifermin, a recombinant human fibroblast growth factor 18. In a 549-patient, multicenter, dose-ranging study, the two highest doses achieved a modest yet statistically significant advantage over placebo in total femorotibial joint cartilage thickness on MRI at 2 years. However, the investigators added that the result was of “uncertain clinical importance,” given the lack of a difference from baseline in total Western Ontario and McMaster Universities OA Index score.
“I’m not sure this is going anywhere,” Dr. Ruderman commented.
Tanezumab, a novel subcutaneously injected monoclonal antibody directed against nerve growth factor, has drawn a lot of attention. In an initial multicenter, phase 3, randomized trial it showed what Dr. Ruderman termed “some modest benefit” on pain and function.
“Very much like everything else in OA, you see a huge placebo effect buried in there,” according to the rheumatologist.
This modest clinical benefit was accompanied by a safety signal at the higher 5-mg dose of tanezumab. Moreover, a second phase 3 trial, this one conducted in nearly 3,000 OA patients and presented at the 2019 annual meeting of the American College of Rheumatology, also raised significant safety concerns at the higher dose. And while the 2.5-mg dose was safer, it was disappointingly no more effective in terms of improvement in pain and function scores than diclofenac at 75 mg twice daily, Dr. Ruderman noted.
Dr. Fleischmann predicted that, given the enormous unmet need for new OA treatments, tanezumab at 2.5 mg will win regulatory approval, but it will be a costly niche drug reserved for the challenging subset of patients who can’t take an NSAID and are poor surgical candidates. (On March 2, 2020, Eli Lilly announced that the Food and Drug Administration had accepted its Biologics License Application for tanezumab for the treatment of chronic pain caused by moderate to severe OA.)
Intra-articular FX006, a microsphere-based, extended-release formulation of triamcinolone, outperformed conventional triamcinolone in a phase 3 clinical trial. However, the placebo-subtracted improvement in pain was modest.
“There’s some marginal benefit here, but over time I’m not sure this adds much to just straight-up triamcinolone,” Dr. Ruderman opined.
Welcome to the wild, wild West
Patients with knee OA ask Dr. Ruderman all the time about the intra-articular injections of platelet-rich plasma (PRP) or mesenchymal stem cells they’ve seen touted on the Internet. As an evidence-based physician, he’s not a fan. A meta-analysis of 14 controlled trials of PRP, none double blind, showed some benefit in terms of pain and function at 3, 6, and 12 months, with little risk of adverse events. However, PRP is being marketed with a hype and claimed efficacy out of all proportion to the actual evidence.
“It’s the wild, wild West out there,” the rheumatologist warned.
He cited a study involving a scripted survey of 179 U.S. clinics offering PRP. The mean price quoted for a unilateral knee injection in a hypothetical 52-year-old man with knee OA was $714, and it’s a cash business, since insurance companies won’t cover PRP. Out of 84 centers that were willing to share their claimed efficacy, 10 quoted 90%-100% rates of good results or symptomatic improvement, 27 claimed 80%-90% efficacy, and 29 quoted figures of 70%-80%, all of which are well above the success rates achieved in the flawed clinical trials.
As for mesenchymal stem cells, “if PRP is the wild, wild West, this is the surface of Mars,” Dr. Ruderman quipped.
These stem cell injections are neither FDA regulated nor approved. There are no barriers to setting up a mesenchymal stem cell injection center, and the number of such centers is skyrocketing. Anybody can set up a center, and there’s essentially no oversight.
“The evidence in this area is really terrible,” the rheumatologist said. He pointed to a meta-analysis of five trials, only two of which were rated by the researchers as having a low risk of bias. The conclusion: There was limited evidence of short-term benefit in pain and function, but no evidence of cartilage repair, which is the chief claimed benefit.
The same group of investigators who queried the PRP clinics also successfully contacted 273 of the proliferating U.S. centers offering direct-to-consumer mesenchymal stem cell therapy. The mean price quoted for a unilateral knee injection was a whopping $5,156, which – like PRP – isn’t covered by insurance. At the 36 clinics responding to a request for their efficacy rates, the mean claim was good results or symptomatic improvement in 82% of treated patients.
Dr. Bugbee didn’t endorse this intervention, which is increasingly popular among his fellow orthopedic surgeons.
“The regulatory pathway drives this. Mesenchymal stem cells are categorized as a minimally manipulated tissue, so the regulatory pathway is easy,” explained Dr. Bugbee. “I talk 9 out of 10 patients out of it because there’s no evidence of disease modification.”
On a brighter note
Radiofrequency ablation and neuromodulation procedures for treatment of symptomatic knee OA make no pretense of being disease modifying, but a new systematic review of 33 published studies deemed of moderate or high methodological quality totaling 1,512 patients documented improved pain, function, and disease-specific quality of life for 3-12 months with minimal complications.
Most of these procedures target the genicular nerve, the sensory nerve that innervates the knee.
“There’s some value here to this,” Dr. Ruderman said. “Our pain folks are actually pretty interested in this. At our center, they’re using this for patients with persistent knee pain after knee replacement, with some success. It’s not an unreasonable approach.”
As part of his examination of the evidence base for OA treatment, Dr. Ruderman looked into an intervention he wasn’t familiar with: acupuncture. He was pleasantly surprised.
“There’s quite a bit of data. There is decent evidence that acupuncture has significant benefit, at least for pain, and is certainly without significant side effects,” according to the rheumatologist.
He cited a review of a dozen systematic reviews of randomized, controlled trials of acupuncture for OA. The Chinese investigators rated the overall quality of the evidence as moderate to low, but with some studies being rated high quality. “That’s not as bad as some of the other stuff I looked at,” Dr. Ruderman said.
Acupuncture was found to be 2.4 times more effective than Western medicine for short-term pain relief, and 4.1 times better in terms of total efficacy, with a lower risk of adverse events than with Western medicine.
Dr. Ruderman reported serving as a consultant for and/or receiving research grants from more than a half-dozen pharmaceutical companies.
EXPERT ANALYSIS FROM RWCS 2020