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It’s been a banner year for treatment advances in systemic lupus erythematosus (SLE), with two drugs gaining approval for lupus nephritis while other promising molecules with novel mechanisms of action advanced smartly through the developmental pipeline, speakers agreed at the 2021 Rheumatology Winter Clinical Symposium.
“I think the most important thing in rheumatology in the last year is where we are now with lupus. With two drugs being approved for lupus nephritis, I think that’s really huge as we talk about treat-to-target,” said Alvin F. Wells, MD, PhD, a rheumatologist in Franklin, Wisc.
Martin Bergman, MD, concurred.
“Lupus has been blowing up in the past year. We have two new medications for lupus nephritis, we have two or three new mechanisms of action for therapy. I think that was one of the biggest things in rheumatology in the past year,” said Dr. Bergman, a rheumatologist at Drexel University in Philadelphia and in private practice in Ridley Park, Pa.
Together with Roy Fleischmann, MD, Dr. Wells spotlighted promising new molecules for the treatment of SLE, giant cell arteritis, vasculitis, rheumatoid arthritis, and osteoarthritis.
SLE
The two drugs approved in recent months specifically for lupus nephritis are voclosporin (Lupkynis) and belimumab (Benlysta), which has been approved for lupus for a decade. Voclosporin, an oral calcineurin inhibitor, is a modification of cyclosporine offering significant advantages over the older drug: It’s more potent, requires no dose titration, has a better safety profile, and is metabolized more quickly.
“A safer and easier-to-use calcineurin inhibitor is going to be huge,” Dr. Wells predicted.
Up for Food and Drug Administration review in the coming year on the basis of the positive phase 3 TULIP-1 and TULIP-2 trials is anifrolumab, a monoclonal antibody that binds to the type 1 interferon receptor subunit 1d. At 52 weeks in the pooled analysis, one or more SLE flares occurred in 33.6% of patients on anifrolumab and 42.9% of placebo-treated controls.
“This is not a blockbuster, but it’s a worthwhile addition, like belimumab,” according to Dr. Fleischmann, a rheumatologist at the University of Texas, Dallas.
Dr. Wells concurred, with a reservation: In a subgroup analysis of the TULIP trials, anifrolumab wasn’t significantly better than placebo in black patients, who tend to have more severe and tough-to-treat renal disease.
“Anifrolumab doesn’t look as effective as some other agents, and I’d be disinclined to give it to my black patients,” the rheumatologist said.
Dr. Fleischmann was far more enthusiastic about obinutuzumab (Gazyva), a humanized anti-CD20 monoclonal antibody already approved for the treatment of chronic lymphocytic leukemia and follicular lymphoma.
“It’s an anti-CD20, like rituximab. But it’s better than rituximab, it’s much more effective,” he said.
He pointed to the phase 2 NOBILITY trial, in which 125 patients with class III/IV lupus nephritis were randomized to a 1,000-mg infusion of obinutuzumab or placebo at weeks 0, 2, 24, and 26 and followed for 2 years. The complete renal response rate at 104 weeks in the obinutuzumab group was 41% and the partial renal response rate was 13%, compared to 23% and 6% in controls. The obinutuzumab group also did significantly better in terms of improvement in complement levels, double-stranded DNA, and estimated glomerular filtration rate. All this was accomplished even though the reduction in peripheral B cells dropped from 93% at week 24 to just 16% at week 104. This suggests that tissue levels of B cells in the kidney, joints, and skin may be more important than circulating B cell levels.
“This looks like a very promising agent for patients with lupus nephritis,” Dr. Wells said. “The fact that they got this long-term effect for 2 years with just four infusions is really impressive.”
Another promising drug is iberdomide, an oral modulator of the E3 ubiquitin ligase complex which decreases plasmacytoid dendritic cells and B cells while increasing T regulatory cells. In a phase 2b clinical trial in 288 patients with active SLE, all on background standard-of-care therapy, a 4-point or greater reduction in the SLE Responder Index (SRI-4) at week 24 was achieved in 54.3% of the group on iberdomide at 0.45 mg/day, a significantly better result than the 34.9% rate with placebo. This absolute 19.4% difference was even greater in the subgroup of patients with a high baseline level of the transcription factor Aiolos, where the absolute improvement over placebo was 32.9%. Similarly, the benefit of iberdomide was also enhanced in patients with a high baseline level of type 1 interferon, where the absolute difference was 26.8%. This raises the prospect that a bioassay could be developed to predict the likelihood of a favorable clinical response to the drug. Iberdomide was well tolerated, with fewer severe adverse events than in the control group.
A humanized monoclonal antibody known for now as BIIB059 demonstrated efficacy and was well tolerated in the phase 2 LILAC trial. BIIB059 binds to blood dendritic cell antigen 2 (BDCA2), a receptor specific to plasmacytoid dendritic cells, resulting in decreased production of type 1 interferon and other inflammatory cytokines. The LILAC trial included 132 SLE patients with active arthritis and skin disease who received subcutaneous injections of BIIB059 at 450 mg or placebo every 4 weeks, with an extra dose at week 2. The primary endpoint was met, with an absolute 15-joint reduction in the total number of tender or swollen joints from baseline to week 24 in the BIIB059 group, compared to an 11.6-joint reduction with placebo. In addition, the likelihood of an SRI-4 response at week 24 was 3.49-fold greater with BIIB059 than with placebo.
Dr. Wells noted that the BIIB059 group showed continued improvement from week 12 to week 24, unlike the response pattern seen with many biologics for rheumatoid arthritis, where a plateau is reached by 8-12 weeks.
Vasculitis
The positive results for the C5a receptor inhibitor avacopan for treatment of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis in the phase-3 ADVOCATE trial have been hailed by some rheumatologists as a major breakthrough, but Dr. Fleischmann isn’t so sure.
The trial randomized 331 patients to oral avacopan at 30 mg twice daily or oral prednisone, with all patients on either cyclophosphamide or rituximab. Avacopan was noninferior to prednisone in terms of remission at week 26, but superior to prednisone for sustained taper at week 52. The rate of serious adverse events was 45.1% with prednisone and 42.2% in the avacopan arm.
“This is a drug that’s going to be much, much more expensive than prednisone. There were people in our group who were ecstatic that this drug is going to come, but how much it’s going to be used, I don’t know,” Dr. Fleischmann said.
Dr. Wells said cost-benefit analyses will be needed in order to learn if avacopan’s anticipated high sticker price is offset by the cost of serious corticosteroid side effects such as avascular necrosis.
Giant cell arteritis
Mavrilimumab is a human monoclonal antibody that inhibits human granulocyte macrophage colony stimulating factor receptor alpha. It demonstrated impressive efficacy in a phase 2, double-blind, randomized, placebo-controlled trial conducted in 70 patients with biopsy-confirmed giant cell arteritis. Participants were on corticosteroids until they went into remission and were then randomized to mavrilimumab or placebo, with the steroids stopped. By week 26, 19% of patients in the mavrilimumab arm had flared, as compared to 46.4% of controls.
“This is a game changer,” Dr. Wells declared. “I struggle with these patients because I can’t get the IL-6 drugs approved for them. I need something else.”
Dr. Fleischmann has a good idea how he’ll use mavrilimumab, if it wins approval: “I think this is clearly a drug you would use in a patient you can’t get off steroids and you’re having all the steroid toxicity. I don’t know that you’d use it right away.”
Osteoarthritis
Dr. Fleischmann predicted that tanezumab, a monoclonal antibody directed against nerve growth factor, will win FDA approval in 2021 for the treatment of osteoarthritis pain in patients with an inadequate response or intolerance to standard-of-care NSAIDs and opioids. But he cautioned his colleagues not to expect too much from the biologic, which has a long and checkered developmental history.
“It works better than placebo. It does not work better than an NSAID or an opioid. So it should be reasonable in patients who cannot take an NSAID or cannot or will not take an opioid,” he said.
There are safety issues to be aware of with tanezumab, he added: clinically significant increased risks of peripheral neuropathy and joint space narrowing.
Rheumatoid arthritis
Dr. Wells thought one of the most interesting novel therapies for RA in the past year didn’t involve a pharmaceutical, but rather noninvasive auricular branch stimulation of the vagus nerve. He cited an open-label, 12-week, uncontrolled study in 27 patients with active RA who wore an ear clip for vagal nerve stimulation for 12 weeks. The mean Disease Activity Score in 28 joints using C-reactive protein (DAS28-CRP) – the primary study endpoint – improved from 6.30 at baseline to 3.76 at week 12. The number of tender joints dropped from 12.17 to 4.7, while the swollen joint count went from 7.0 to 3.44. Pain scores improved from 75.23 to 43.3. Scores on the Health Assessment Questionnaire Disability Index improved from 1.59 to 1.05. There was no significant change in CRP. All in all, a modest clinical effect achieved noninvasively.
“The thing that did it for me was the effect on MRI from baseline: decreased synovitis, osteitis, and bone erosion scores,” Dr. Wells said. “This is noninvasive, so patients who want to do medical marijuana or CBD can put an earring on their auricular nerve.”
Dr. Fleischmann scoffed. “An open-label study, 27 patients? Let me see the real study,” he quipped.
Dr. Fleischmann reported receiving clinical trial research grants from and serving as a consultant to more than a dozen pharmaceutical companies. Dr. Wells serves as a consultant to MiCare Path.
It’s been a banner year for treatment advances in systemic lupus erythematosus (SLE), with two drugs gaining approval for lupus nephritis while other promising molecules with novel mechanisms of action advanced smartly through the developmental pipeline, speakers agreed at the 2021 Rheumatology Winter Clinical Symposium.
“I think the most important thing in rheumatology in the last year is where we are now with lupus. With two drugs being approved for lupus nephritis, I think that’s really huge as we talk about treat-to-target,” said Alvin F. Wells, MD, PhD, a rheumatologist in Franklin, Wisc.
Martin Bergman, MD, concurred.
“Lupus has been blowing up in the past year. We have two new medications for lupus nephritis, we have two or three new mechanisms of action for therapy. I think that was one of the biggest things in rheumatology in the past year,” said Dr. Bergman, a rheumatologist at Drexel University in Philadelphia and in private practice in Ridley Park, Pa.
Together with Roy Fleischmann, MD, Dr. Wells spotlighted promising new molecules for the treatment of SLE, giant cell arteritis, vasculitis, rheumatoid arthritis, and osteoarthritis.
SLE
The two drugs approved in recent months specifically for lupus nephritis are voclosporin (Lupkynis) and belimumab (Benlysta), which has been approved for lupus for a decade. Voclosporin, an oral calcineurin inhibitor, is a modification of cyclosporine offering significant advantages over the older drug: It’s more potent, requires no dose titration, has a better safety profile, and is metabolized more quickly.
“A safer and easier-to-use calcineurin inhibitor is going to be huge,” Dr. Wells predicted.
Up for Food and Drug Administration review in the coming year on the basis of the positive phase 3 TULIP-1 and TULIP-2 trials is anifrolumab, a monoclonal antibody that binds to the type 1 interferon receptor subunit 1d. At 52 weeks in the pooled analysis, one or more SLE flares occurred in 33.6% of patients on anifrolumab and 42.9% of placebo-treated controls.
“This is not a blockbuster, but it’s a worthwhile addition, like belimumab,” according to Dr. Fleischmann, a rheumatologist at the University of Texas, Dallas.
Dr. Wells concurred, with a reservation: In a subgroup analysis of the TULIP trials, anifrolumab wasn’t significantly better than placebo in black patients, who tend to have more severe and tough-to-treat renal disease.
“Anifrolumab doesn’t look as effective as some other agents, and I’d be disinclined to give it to my black patients,” the rheumatologist said.
Dr. Fleischmann was far more enthusiastic about obinutuzumab (Gazyva), a humanized anti-CD20 monoclonal antibody already approved for the treatment of chronic lymphocytic leukemia and follicular lymphoma.
“It’s an anti-CD20, like rituximab. But it’s better than rituximab, it’s much more effective,” he said.
He pointed to the phase 2 NOBILITY trial, in which 125 patients with class III/IV lupus nephritis were randomized to a 1,000-mg infusion of obinutuzumab or placebo at weeks 0, 2, 24, and 26 and followed for 2 years. The complete renal response rate at 104 weeks in the obinutuzumab group was 41% and the partial renal response rate was 13%, compared to 23% and 6% in controls. The obinutuzumab group also did significantly better in terms of improvement in complement levels, double-stranded DNA, and estimated glomerular filtration rate. All this was accomplished even though the reduction in peripheral B cells dropped from 93% at week 24 to just 16% at week 104. This suggests that tissue levels of B cells in the kidney, joints, and skin may be more important than circulating B cell levels.
“This looks like a very promising agent for patients with lupus nephritis,” Dr. Wells said. “The fact that they got this long-term effect for 2 years with just four infusions is really impressive.”
Another promising drug is iberdomide, an oral modulator of the E3 ubiquitin ligase complex which decreases plasmacytoid dendritic cells and B cells while increasing T regulatory cells. In a phase 2b clinical trial in 288 patients with active SLE, all on background standard-of-care therapy, a 4-point or greater reduction in the SLE Responder Index (SRI-4) at week 24 was achieved in 54.3% of the group on iberdomide at 0.45 mg/day, a significantly better result than the 34.9% rate with placebo. This absolute 19.4% difference was even greater in the subgroup of patients with a high baseline level of the transcription factor Aiolos, where the absolute improvement over placebo was 32.9%. Similarly, the benefit of iberdomide was also enhanced in patients with a high baseline level of type 1 interferon, where the absolute difference was 26.8%. This raises the prospect that a bioassay could be developed to predict the likelihood of a favorable clinical response to the drug. Iberdomide was well tolerated, with fewer severe adverse events than in the control group.
A humanized monoclonal antibody known for now as BIIB059 demonstrated efficacy and was well tolerated in the phase 2 LILAC trial. BIIB059 binds to blood dendritic cell antigen 2 (BDCA2), a receptor specific to plasmacytoid dendritic cells, resulting in decreased production of type 1 interferon and other inflammatory cytokines. The LILAC trial included 132 SLE patients with active arthritis and skin disease who received subcutaneous injections of BIIB059 at 450 mg or placebo every 4 weeks, with an extra dose at week 2. The primary endpoint was met, with an absolute 15-joint reduction in the total number of tender or swollen joints from baseline to week 24 in the BIIB059 group, compared to an 11.6-joint reduction with placebo. In addition, the likelihood of an SRI-4 response at week 24 was 3.49-fold greater with BIIB059 than with placebo.
Dr. Wells noted that the BIIB059 group showed continued improvement from week 12 to week 24, unlike the response pattern seen with many biologics for rheumatoid arthritis, where a plateau is reached by 8-12 weeks.
Vasculitis
The positive results for the C5a receptor inhibitor avacopan for treatment of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis in the phase-3 ADVOCATE trial have been hailed by some rheumatologists as a major breakthrough, but Dr. Fleischmann isn’t so sure.
The trial randomized 331 patients to oral avacopan at 30 mg twice daily or oral prednisone, with all patients on either cyclophosphamide or rituximab. Avacopan was noninferior to prednisone in terms of remission at week 26, but superior to prednisone for sustained taper at week 52. The rate of serious adverse events was 45.1% with prednisone and 42.2% in the avacopan arm.
“This is a drug that’s going to be much, much more expensive than prednisone. There were people in our group who were ecstatic that this drug is going to come, but how much it’s going to be used, I don’t know,” Dr. Fleischmann said.
Dr. Wells said cost-benefit analyses will be needed in order to learn if avacopan’s anticipated high sticker price is offset by the cost of serious corticosteroid side effects such as avascular necrosis.
Giant cell arteritis
Mavrilimumab is a human monoclonal antibody that inhibits human granulocyte macrophage colony stimulating factor receptor alpha. It demonstrated impressive efficacy in a phase 2, double-blind, randomized, placebo-controlled trial conducted in 70 patients with biopsy-confirmed giant cell arteritis. Participants were on corticosteroids until they went into remission and were then randomized to mavrilimumab or placebo, with the steroids stopped. By week 26, 19% of patients in the mavrilimumab arm had flared, as compared to 46.4% of controls.
“This is a game changer,” Dr. Wells declared. “I struggle with these patients because I can’t get the IL-6 drugs approved for them. I need something else.”
Dr. Fleischmann has a good idea how he’ll use mavrilimumab, if it wins approval: “I think this is clearly a drug you would use in a patient you can’t get off steroids and you’re having all the steroid toxicity. I don’t know that you’d use it right away.”
Osteoarthritis
Dr. Fleischmann predicted that tanezumab, a monoclonal antibody directed against nerve growth factor, will win FDA approval in 2021 for the treatment of osteoarthritis pain in patients with an inadequate response or intolerance to standard-of-care NSAIDs and opioids. But he cautioned his colleagues not to expect too much from the biologic, which has a long and checkered developmental history.
“It works better than placebo. It does not work better than an NSAID or an opioid. So it should be reasonable in patients who cannot take an NSAID or cannot or will not take an opioid,” he said.
There are safety issues to be aware of with tanezumab, he added: clinically significant increased risks of peripheral neuropathy and joint space narrowing.
Rheumatoid arthritis
Dr. Wells thought one of the most interesting novel therapies for RA in the past year didn’t involve a pharmaceutical, but rather noninvasive auricular branch stimulation of the vagus nerve. He cited an open-label, 12-week, uncontrolled study in 27 patients with active RA who wore an ear clip for vagal nerve stimulation for 12 weeks. The mean Disease Activity Score in 28 joints using C-reactive protein (DAS28-CRP) – the primary study endpoint – improved from 6.30 at baseline to 3.76 at week 12. The number of tender joints dropped from 12.17 to 4.7, while the swollen joint count went from 7.0 to 3.44. Pain scores improved from 75.23 to 43.3. Scores on the Health Assessment Questionnaire Disability Index improved from 1.59 to 1.05. There was no significant change in CRP. All in all, a modest clinical effect achieved noninvasively.
“The thing that did it for me was the effect on MRI from baseline: decreased synovitis, osteitis, and bone erosion scores,” Dr. Wells said. “This is noninvasive, so patients who want to do medical marijuana or CBD can put an earring on their auricular nerve.”
Dr. Fleischmann scoffed. “An open-label study, 27 patients? Let me see the real study,” he quipped.
Dr. Fleischmann reported receiving clinical trial research grants from and serving as a consultant to more than a dozen pharmaceutical companies. Dr. Wells serves as a consultant to MiCare Path.
It’s been a banner year for treatment advances in systemic lupus erythematosus (SLE), with two drugs gaining approval for lupus nephritis while other promising molecules with novel mechanisms of action advanced smartly through the developmental pipeline, speakers agreed at the 2021 Rheumatology Winter Clinical Symposium.
“I think the most important thing in rheumatology in the last year is where we are now with lupus. With two drugs being approved for lupus nephritis, I think that’s really huge as we talk about treat-to-target,” said Alvin F. Wells, MD, PhD, a rheumatologist in Franklin, Wisc.
Martin Bergman, MD, concurred.
“Lupus has been blowing up in the past year. We have two new medications for lupus nephritis, we have two or three new mechanisms of action for therapy. I think that was one of the biggest things in rheumatology in the past year,” said Dr. Bergman, a rheumatologist at Drexel University in Philadelphia and in private practice in Ridley Park, Pa.
Together with Roy Fleischmann, MD, Dr. Wells spotlighted promising new molecules for the treatment of SLE, giant cell arteritis, vasculitis, rheumatoid arthritis, and osteoarthritis.
SLE
The two drugs approved in recent months specifically for lupus nephritis are voclosporin (Lupkynis) and belimumab (Benlysta), which has been approved for lupus for a decade. Voclosporin, an oral calcineurin inhibitor, is a modification of cyclosporine offering significant advantages over the older drug: It’s more potent, requires no dose titration, has a better safety profile, and is metabolized more quickly.
“A safer and easier-to-use calcineurin inhibitor is going to be huge,” Dr. Wells predicted.
Up for Food and Drug Administration review in the coming year on the basis of the positive phase 3 TULIP-1 and TULIP-2 trials is anifrolumab, a monoclonal antibody that binds to the type 1 interferon receptor subunit 1d. At 52 weeks in the pooled analysis, one or more SLE flares occurred in 33.6% of patients on anifrolumab and 42.9% of placebo-treated controls.
“This is not a blockbuster, but it’s a worthwhile addition, like belimumab,” according to Dr. Fleischmann, a rheumatologist at the University of Texas, Dallas.
Dr. Wells concurred, with a reservation: In a subgroup analysis of the TULIP trials, anifrolumab wasn’t significantly better than placebo in black patients, who tend to have more severe and tough-to-treat renal disease.
“Anifrolumab doesn’t look as effective as some other agents, and I’d be disinclined to give it to my black patients,” the rheumatologist said.
Dr. Fleischmann was far more enthusiastic about obinutuzumab (Gazyva), a humanized anti-CD20 monoclonal antibody already approved for the treatment of chronic lymphocytic leukemia and follicular lymphoma.
“It’s an anti-CD20, like rituximab. But it’s better than rituximab, it’s much more effective,” he said.
He pointed to the phase 2 NOBILITY trial, in which 125 patients with class III/IV lupus nephritis were randomized to a 1,000-mg infusion of obinutuzumab or placebo at weeks 0, 2, 24, and 26 and followed for 2 years. The complete renal response rate at 104 weeks in the obinutuzumab group was 41% and the partial renal response rate was 13%, compared to 23% and 6% in controls. The obinutuzumab group also did significantly better in terms of improvement in complement levels, double-stranded DNA, and estimated glomerular filtration rate. All this was accomplished even though the reduction in peripheral B cells dropped from 93% at week 24 to just 16% at week 104. This suggests that tissue levels of B cells in the kidney, joints, and skin may be more important than circulating B cell levels.
“This looks like a very promising agent for patients with lupus nephritis,” Dr. Wells said. “The fact that they got this long-term effect for 2 years with just four infusions is really impressive.”
Another promising drug is iberdomide, an oral modulator of the E3 ubiquitin ligase complex which decreases plasmacytoid dendritic cells and B cells while increasing T regulatory cells. In a phase 2b clinical trial in 288 patients with active SLE, all on background standard-of-care therapy, a 4-point or greater reduction in the SLE Responder Index (SRI-4) at week 24 was achieved in 54.3% of the group on iberdomide at 0.45 mg/day, a significantly better result than the 34.9% rate with placebo. This absolute 19.4% difference was even greater in the subgroup of patients with a high baseline level of the transcription factor Aiolos, where the absolute improvement over placebo was 32.9%. Similarly, the benefit of iberdomide was also enhanced in patients with a high baseline level of type 1 interferon, where the absolute difference was 26.8%. This raises the prospect that a bioassay could be developed to predict the likelihood of a favorable clinical response to the drug. Iberdomide was well tolerated, with fewer severe adverse events than in the control group.
A humanized monoclonal antibody known for now as BIIB059 demonstrated efficacy and was well tolerated in the phase 2 LILAC trial. BIIB059 binds to blood dendritic cell antigen 2 (BDCA2), a receptor specific to plasmacytoid dendritic cells, resulting in decreased production of type 1 interferon and other inflammatory cytokines. The LILAC trial included 132 SLE patients with active arthritis and skin disease who received subcutaneous injections of BIIB059 at 450 mg or placebo every 4 weeks, with an extra dose at week 2. The primary endpoint was met, with an absolute 15-joint reduction in the total number of tender or swollen joints from baseline to week 24 in the BIIB059 group, compared to an 11.6-joint reduction with placebo. In addition, the likelihood of an SRI-4 response at week 24 was 3.49-fold greater with BIIB059 than with placebo.
Dr. Wells noted that the BIIB059 group showed continued improvement from week 12 to week 24, unlike the response pattern seen with many biologics for rheumatoid arthritis, where a plateau is reached by 8-12 weeks.
Vasculitis
The positive results for the C5a receptor inhibitor avacopan for treatment of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis in the phase-3 ADVOCATE trial have been hailed by some rheumatologists as a major breakthrough, but Dr. Fleischmann isn’t so sure.
The trial randomized 331 patients to oral avacopan at 30 mg twice daily or oral prednisone, with all patients on either cyclophosphamide or rituximab. Avacopan was noninferior to prednisone in terms of remission at week 26, but superior to prednisone for sustained taper at week 52. The rate of serious adverse events was 45.1% with prednisone and 42.2% in the avacopan arm.
“This is a drug that’s going to be much, much more expensive than prednisone. There were people in our group who were ecstatic that this drug is going to come, but how much it’s going to be used, I don’t know,” Dr. Fleischmann said.
Dr. Wells said cost-benefit analyses will be needed in order to learn if avacopan’s anticipated high sticker price is offset by the cost of serious corticosteroid side effects such as avascular necrosis.
Giant cell arteritis
Mavrilimumab is a human monoclonal antibody that inhibits human granulocyte macrophage colony stimulating factor receptor alpha. It demonstrated impressive efficacy in a phase 2, double-blind, randomized, placebo-controlled trial conducted in 70 patients with biopsy-confirmed giant cell arteritis. Participants were on corticosteroids until they went into remission and were then randomized to mavrilimumab or placebo, with the steroids stopped. By week 26, 19% of patients in the mavrilimumab arm had flared, as compared to 46.4% of controls.
“This is a game changer,” Dr. Wells declared. “I struggle with these patients because I can’t get the IL-6 drugs approved for them. I need something else.”
Dr. Fleischmann has a good idea how he’ll use mavrilimumab, if it wins approval: “I think this is clearly a drug you would use in a patient you can’t get off steroids and you’re having all the steroid toxicity. I don’t know that you’d use it right away.”
Osteoarthritis
Dr. Fleischmann predicted that tanezumab, a monoclonal antibody directed against nerve growth factor, will win FDA approval in 2021 for the treatment of osteoarthritis pain in patients with an inadequate response or intolerance to standard-of-care NSAIDs and opioids. But he cautioned his colleagues not to expect too much from the biologic, which has a long and checkered developmental history.
“It works better than placebo. It does not work better than an NSAID or an opioid. So it should be reasonable in patients who cannot take an NSAID or cannot or will not take an opioid,” he said.
There are safety issues to be aware of with tanezumab, he added: clinically significant increased risks of peripheral neuropathy and joint space narrowing.
Rheumatoid arthritis
Dr. Wells thought one of the most interesting novel therapies for RA in the past year didn’t involve a pharmaceutical, but rather noninvasive auricular branch stimulation of the vagus nerve. He cited an open-label, 12-week, uncontrolled study in 27 patients with active RA who wore an ear clip for vagal nerve stimulation for 12 weeks. The mean Disease Activity Score in 28 joints using C-reactive protein (DAS28-CRP) – the primary study endpoint – improved from 6.30 at baseline to 3.76 at week 12. The number of tender joints dropped from 12.17 to 4.7, while the swollen joint count went from 7.0 to 3.44. Pain scores improved from 75.23 to 43.3. Scores on the Health Assessment Questionnaire Disability Index improved from 1.59 to 1.05. There was no significant change in CRP. All in all, a modest clinical effect achieved noninvasively.
“The thing that did it for me was the effect on MRI from baseline: decreased synovitis, osteitis, and bone erosion scores,” Dr. Wells said. “This is noninvasive, so patients who want to do medical marijuana or CBD can put an earring on their auricular nerve.”
Dr. Fleischmann scoffed. “An open-label study, 27 patients? Let me see the real study,” he quipped.
Dr. Fleischmann reported receiving clinical trial research grants from and serving as a consultant to more than a dozen pharmaceutical companies. Dr. Wells serves as a consultant to MiCare Path.
FROM RWCS 2021