Joan Merrill, MD

Lupus nephritis (LN) affects approximately 25%-60% of patients with systemic lupus erythematosus. Currently, guideline-directed therapy recommends a combination of steroids plus either mycophenolate mofetil or cyclophosphamide. Despite treatment, about 10%-30% of LN patients will progress to end-stage kidney disease. 

Fortunately, over the past 2 years, the FDA approved two novel agents that expand treatment options for patients with active disease who have received standard-of-care therapy.  

In this ReCAP, Dr Joan Merrill, of the University of Oklahoma Health Sciences Center, reports on the B-lymphocyte stimulator–specific inhibitor belimumab, which was evaluated in the BLISS-LN trial, and the oral calcineurin inhibitor voclosporin, which was assessed in the AURORA trials.  

Dr Merrill discusses how these recently approved medications fit into the standard of care for LN patients. 

--

Joan Merrill, MD, Professor, Department of Medicine, Division of Rheumatology, University of Oklahoma Health Sciences Center; Director of Clinical Projects, Arthritis & Clinical Immunology Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma 

Joan Merrill, MD, has disclosed the following relevant financial relationships: 

Serve(d) as a speaker or a member of a speakers bureau for: Biogen 

Received research grant from: Bristol-Myers Squibb; GlaxoSmithKline 

Received income in an amount equal to or greater than $250 from: AbbVie; Alexion; Amgen; AstraZeneca; Aurinia; Bristol-Myers Squibb; EMD Serono; Genentech; Gilead; GlaxoSmithKline; Lilly; Merck; Provention; RemeGen; Sanofi; UCB; Zenas 

Received research grant from: AbbVie; AstraZeneca; BeiGene; Pharmacyclics; TG Therapeutics 

Lupus nephritis (LN) affects approximately 25%-60% of patients with systemic lupus erythematosus. Currently, guideline-directed therapy recommends a combination of steroids plus either mycophenolate mofetil or cyclophosphamide. Despite treatment, about 10%-30% of LN patients will progress to end-stage kidney disease. 

Fortunately, over the past 2 years, the FDA approved two novel agents that expand treatment options for patients with active disease who have received standard-of-care therapy.  

In this ReCAP, Dr Joan Merrill, of the University of Oklahoma Health Sciences Center, reports on the B-lymphocyte stimulator–specific inhibitor belimumab, which was evaluated in the BLISS-LN trial, and the oral calcineurin inhibitor voclosporin, which was assessed in the AURORA trials.  

Dr Merrill discusses how these recently approved medications fit into the standard of care for LN patients. 

--

Joan Merrill, MD, Professor, Department of Medicine, Division of Rheumatology, University of Oklahoma Health Sciences Center; Director of Clinical Projects, Arthritis & Clinical Immunology Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma 

Joan Merrill, MD, has disclosed the following relevant financial relationships: 

Serve(d) as a speaker or a member of a speakers bureau for: Biogen 

Received research grant from: Bristol-Myers Squibb; GlaxoSmithKline 

Received income in an amount equal to or greater than $250 from: AbbVie; Alexion; Amgen; AstraZeneca; Aurinia; Bristol-Myers Squibb; EMD Serono; Genentech; Gilead; GlaxoSmithKline; Lilly; Merck; Provention; RemeGen; Sanofi; UCB; Zenas 

Received research grant from: AbbVie; AstraZeneca; BeiGene; Pharmacyclics; TG Therapeutics 

Lupus nephritis (LN) affects approximately 25%-60% of patients with systemic lupus erythematosus. Currently, guideline-directed therapy recommends a combination of steroids plus either mycophenolate mofetil or cyclophosphamide. Despite treatment, about 10%-30% of LN patients will progress to end-stage kidney disease. 

Fortunately, over the past 2 years, the FDA approved two novel agents that expand treatment options for patients with active disease who have received standard-of-care therapy.  

In this ReCAP, Dr Joan Merrill, of the University of Oklahoma Health Sciences Center, reports on the B-lymphocyte stimulator–specific inhibitor belimumab, which was evaluated in the BLISS-LN trial, and the oral calcineurin inhibitor voclosporin, which was assessed in the AURORA trials.  

Dr Merrill discusses how these recently approved medications fit into the standard of care for LN patients. 

--

Joan Merrill, MD, Professor, Department of Medicine, Division of Rheumatology, University of Oklahoma Health Sciences Center; Director of Clinical Projects, Arthritis & Clinical Immunology Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma 

Joan Merrill, MD, has disclosed the following relevant financial relationships: 

Serve(d) as a speaker or a member of a speakers bureau for: Biogen 

Received research grant from: Bristol-Myers Squibb; GlaxoSmithKline 

Received income in an amount equal to or greater than $250 from: AbbVie; Alexion; Amgen; AstraZeneca; Aurinia; Bristol-Myers Squibb; EMD Serono; Genentech; Gilead; GlaxoSmithKline; Lilly; Merck; Provention; RemeGen; Sanofi; UCB; Zenas 

Received research grant from: AbbVie; AstraZeneca; BeiGene; Pharmacyclics; TG Therapeutics 

Dr Joan Merrill, of the Oklahoma Medical Research Foundation in Oklahoma City, reviews updates on several treatment options for systemic lupus erythematosus that were presented at the 2021 ACR Convergence.  

Dr Merrill begins by sharing data from a phase 2 study in which she and her colleagues investigated the efficacy and safety data for iberdomide. The novel agent was associated with sustained clinical benefits in multiple measures of disease activity and was well tolerated through week 52.  

Next, she reports on a post-hoc analysis of the BLISS-LN trial that evaluated the effects of belimumab plus standard therapy on renal outcomes in patients with or without steroid pulses during induction therapy. The study found that belimumab improved kidney outcomes compared with placebo, regardless of whether steroid pulses were administered. However, it was also observed that prevention of lupus nephritis flares was more prominent in patients who received steroid pulses.  

Finally, Dr Merrill highlights a late-breaking poster that reported results from BLISS-BELIEVE, a study evaluating the efficacy and safety of belimumab plus rituximab. Although adding a single cycle of rituximab to belimumab did not improve disease control or remission, the study found that duration of disease control at week 52 and SLEDAI-2K reductions at week 104 were significantly greater in this group compared with the belimumab-plus-placebo group. However, there were also more serious infections reported in the belimumab-plus-rituximab group. 

--

Joan Merrill, MD, Professor, Department of Medicine, University of Oklahoma Health Sciences Center; Director of Clinical Projects, Arthritis & Clinical Immunology Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma 

Joan Merrill, MD, has disclosed the following relevant financial relationships: Serve(d) as a speaker or a member of a speakers bureau for: Biogen 

Received research grant from: AstraZeneca 

Received income in an amount equal to or greater than $250 from: AbbVie; Amgen; AstraZeneca; Aurinia; Biogen; BMS; EMD Serono; Genentech; GSK; Janssen; Provention; RemeGen; Sanofi; UCB; Zenas 

Dr Joan Merrill, of the Oklahoma Medical Research Foundation in Oklahoma City, reviews updates on several treatment options for systemic lupus erythematosus that were presented at the 2021 ACR Convergence.  

Dr Merrill begins by sharing data from a phase 2 study in which she and her colleagues investigated the efficacy and safety data for iberdomide. The novel agent was associated with sustained clinical benefits in multiple measures of disease activity and was well tolerated through week 52.  

Next, she reports on a post-hoc analysis of the BLISS-LN trial that evaluated the effects of belimumab plus standard therapy on renal outcomes in patients with or without steroid pulses during induction therapy. The study found that belimumab improved kidney outcomes compared with placebo, regardless of whether steroid pulses were administered. However, it was also observed that prevention of lupus nephritis flares was more prominent in patients who received steroid pulses.  

Finally, Dr Merrill highlights a late-breaking poster that reported results from BLISS-BELIEVE, a study evaluating the efficacy and safety of belimumab plus rituximab. Although adding a single cycle of rituximab to belimumab did not improve disease control or remission, the study found that duration of disease control at week 52 and SLEDAI-2K reductions at week 104 were significantly greater in this group compared with the belimumab-plus-placebo group. However, there were also more serious infections reported in the belimumab-plus-rituximab group. 

--

Joan Merrill, MD, Professor, Department of Medicine, University of Oklahoma Health Sciences Center; Director of Clinical Projects, Arthritis & Clinical Immunology Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma 

Joan Merrill, MD, has disclosed the following relevant financial relationships: Serve(d) as a speaker or a member of a speakers bureau for: Biogen 

Received research grant from: AstraZeneca 

Received income in an amount equal to or greater than $250 from: AbbVie; Amgen; AstraZeneca; Aurinia; Biogen; BMS; EMD Serono; Genentech; GSK; Janssen; Provention; RemeGen; Sanofi; UCB; Zenas 

Dr Joan Merrill, of the Oklahoma Medical Research Foundation in Oklahoma City, reviews updates on several treatment options for systemic lupus erythematosus that were presented at the 2021 ACR Convergence.  

Dr Merrill begins by sharing data from a phase 2 study in which she and her colleagues investigated the efficacy and safety data for iberdomide. The novel agent was associated with sustained clinical benefits in multiple measures of disease activity and was well tolerated through week 52.  

Next, she reports on a post-hoc analysis of the BLISS-LN trial that evaluated the effects of belimumab plus standard therapy on renal outcomes in patients with or without steroid pulses during induction therapy. The study found that belimumab improved kidney outcomes compared with placebo, regardless of whether steroid pulses were administered. However, it was also observed that prevention of lupus nephritis flares was more prominent in patients who received steroid pulses.  

Finally, Dr Merrill highlights a late-breaking poster that reported results from BLISS-BELIEVE, a study evaluating the efficacy and safety of belimumab plus rituximab. Although adding a single cycle of rituximab to belimumab did not improve disease control or remission, the study found that duration of disease control at week 52 and SLEDAI-2K reductions at week 104 were significantly greater in this group compared with the belimumab-plus-placebo group. However, there were also more serious infections reported in the belimumab-plus-rituximab group. 

--

Joan Merrill, MD, Professor, Department of Medicine, University of Oklahoma Health Sciences Center; Director of Clinical Projects, Arthritis & Clinical Immunology Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma 

Joan Merrill, MD, has disclosed the following relevant financial relationships: Serve(d) as a speaker or a member of a speakers bureau for: Biogen 

Received research grant from: AstraZeneca 

Received income in an amount equal to or greater than $250 from: AbbVie; Amgen; AstraZeneca; Aurinia; Biogen; BMS; EMD Serono; Genentech; GSK; Janssen; Provention; RemeGen; Sanofi; UCB; Zenas 

Editor’s note: This commentary relates to the story, “New classification system for systemic lupus erythematosus moves forward.”



While work to develop a new set of lupus classification criteria more suitable for clinical research is important, the Lupus Foundation of America believes the current work is going in the wrong direction.

Increasingly, key opinion leaders understand lupus to be a spectrum of disease, and there is ample justification of this from scientific evidence (Nat Rev Rheumatol. 2015;11[7]:385-6) The criteria being worked on by ACR and EULAR draws upon an archaic concept with the musty name of “systemic lupus erythematosus,” which relies on a 19th century approach to categorizing disease by counting the signs and symptoms instead of by modern concepts of pathophysiology and prognostic severity. This imposes a homogeneity on the population that simply does not exist. Attempts to re-order obsolescent arrays of organs and autoantibodies to classify lupus will be futile, especially if the aim is to improve the rationale for clinical trial recruitment. Recent clinical trials and modern immunologic methods have already demonstrated, beyond a doubt, that subsets of patients, definable by gene expression patterns or state of the art pharmacodynamic responses, do or do not respond to individual targeted treatments. We now know that patients who require different treatments may well share many of their symptoms in many of the same organs, and this fact defies the outmoded, abacus-based approach to disease classification.

We are concerned that redefining SLE by weighting all disease in one organ as more or less impactful than all disease in another organ flies in the face of current scientific knowledge. If this is the direction in which the effort is going, there is the potential for a negative impact on drug development, clinical care, and access to treatment. The term itself, “SLE,” interferes with selecting appropriate lupus patients for participation in trials. Many people have moderate and even severe lupus syndromes who do not meet enough criteria to be labeled “SLE” (for example, immune thrombocytopenia, hemolytic anemia, discoid lupus, or subacute cutaneous lupus, which can cause severe rashes covering wide areas of the body). In this iteration, assigning less weight to cutaneous lupus as currently proposed is not just problematic, it will set the field back.

By not viewing cutaneous lupus as part of the lupus spectrum, we develop a false sense that this subset of people with lupus will not progress to “SLE,” yet many of them do. Even those who do not later develop features in other organs besides the skin may have more severe disease than other patients who do. Minimizing the “score” for cutaneous lupus will lead to individuals who carry a significant burden of disease being barred from trials, and from access to the treatments they need, once approved.

Conversely, people who do meet criteria for “SLE” under any algorithm, past or present, may have a range of severity, from very severe to very mild. The very mild patients (who may have, in their lifetime met the multiorgan criteria) are entering trials in large numbers and contributing to the high placebo responses which have stopped many promising investigational treatments from further development. Additionally, the common misuse of the current classification criteria as diagnostic criteria has become an unacceptable norm in the lupus community. This leads us to believe that new criteria will continue to be misused, further disenfranchising a huge segment of the population who have lupus from access to state-of-the-art research and care.

Advancing the development new classification criteria deserves a wider discussion among the field’s stakeholders, particularly those with expertise in clinical trial outcomes and the clinical care of the full spectrum of lupus patients.
 

Sandra C. Raymond is CEO and President, Leslie M. Hanrahan is VP of Education and Research, and Joan Merrill, MD, is the Chief Adviser for Clinical Development at the Lupus Foundation of America. Dr. Merrill is also the Oklahoma Medical Research Foundation Professor of Medicine at the University of Oklahoma, Oklahoma City.

Editor’s note: This commentary relates to the story, “New classification system for systemic lupus erythematosus moves forward.”



While work to develop a new set of lupus classification criteria more suitable for clinical research is important, the Lupus Foundation of America believes the current work is going in the wrong direction.

Increasingly, key opinion leaders understand lupus to be a spectrum of disease, and there is ample justification of this from scientific evidence (Nat Rev Rheumatol. 2015;11[7]:385-6) The criteria being worked on by ACR and EULAR draws upon an archaic concept with the musty name of “systemic lupus erythematosus,” which relies on a 19th century approach to categorizing disease by counting the signs and symptoms instead of by modern concepts of pathophysiology and prognostic severity. This imposes a homogeneity on the population that simply does not exist. Attempts to re-order obsolescent arrays of organs and autoantibodies to classify lupus will be futile, especially if the aim is to improve the rationale for clinical trial recruitment. Recent clinical trials and modern immunologic methods have already demonstrated, beyond a doubt, that subsets of patients, definable by gene expression patterns or state of the art pharmacodynamic responses, do or do not respond to individual targeted treatments. We now know that patients who require different treatments may well share many of their symptoms in many of the same organs, and this fact defies the outmoded, abacus-based approach to disease classification.

We are concerned that redefining SLE by weighting all disease in one organ as more or less impactful than all disease in another organ flies in the face of current scientific knowledge. If this is the direction in which the effort is going, there is the potential for a negative impact on drug development, clinical care, and access to treatment. The term itself, “SLE,” interferes with selecting appropriate lupus patients for participation in trials. Many people have moderate and even severe lupus syndromes who do not meet enough criteria to be labeled “SLE” (for example, immune thrombocytopenia, hemolytic anemia, discoid lupus, or subacute cutaneous lupus, which can cause severe rashes covering wide areas of the body). In this iteration, assigning less weight to cutaneous lupus as currently proposed is not just problematic, it will set the field back.

By not viewing cutaneous lupus as part of the lupus spectrum, we develop a false sense that this subset of people with lupus will not progress to “SLE,” yet many of them do. Even those who do not later develop features in other organs besides the skin may have more severe disease than other patients who do. Minimizing the “score” for cutaneous lupus will lead to individuals who carry a significant burden of disease being barred from trials, and from access to the treatments they need, once approved.

Conversely, people who do meet criteria for “SLE” under any algorithm, past or present, may have a range of severity, from very severe to very mild. The very mild patients (who may have, in their lifetime met the multiorgan criteria) are entering trials in large numbers and contributing to the high placebo responses which have stopped many promising investigational treatments from further development. Additionally, the common misuse of the current classification criteria as diagnostic criteria has become an unacceptable norm in the lupus community. This leads us to believe that new criteria will continue to be misused, further disenfranchising a huge segment of the population who have lupus from access to state-of-the-art research and care.

Advancing the development new classification criteria deserves a wider discussion among the field’s stakeholders, particularly those with expertise in clinical trial outcomes and the clinical care of the full spectrum of lupus patients.
 

Sandra C. Raymond is CEO and President, Leslie M. Hanrahan is VP of Education and Research, and Joan Merrill, MD, is the Chief Adviser for Clinical Development at the Lupus Foundation of America. Dr. Merrill is also the Oklahoma Medical Research Foundation Professor of Medicine at the University of Oklahoma, Oklahoma City.

Editor’s note: This commentary relates to the story, “New classification system for systemic lupus erythematosus moves forward.”



While work to develop a new set of lupus classification criteria more suitable for clinical research is important, the Lupus Foundation of America believes the current work is going in the wrong direction.

Increasingly, key opinion leaders understand lupus to be a spectrum of disease, and there is ample justification of this from scientific evidence (Nat Rev Rheumatol. 2015;11[7]:385-6) The criteria being worked on by ACR and EULAR draws upon an archaic concept with the musty name of “systemic lupus erythematosus,” which relies on a 19th century approach to categorizing disease by counting the signs and symptoms instead of by modern concepts of pathophysiology and prognostic severity. This imposes a homogeneity on the population that simply does not exist. Attempts to re-order obsolescent arrays of organs and autoantibodies to classify lupus will be futile, especially if the aim is to improve the rationale for clinical trial recruitment. Recent clinical trials and modern immunologic methods have already demonstrated, beyond a doubt, that subsets of patients, definable by gene expression patterns or state of the art pharmacodynamic responses, do or do not respond to individual targeted treatments. We now know that patients who require different treatments may well share many of their symptoms in many of the same organs, and this fact defies the outmoded, abacus-based approach to disease classification.

We are concerned that redefining SLE by weighting all disease in one organ as more or less impactful than all disease in another organ flies in the face of current scientific knowledge. If this is the direction in which the effort is going, there is the potential for a negative impact on drug development, clinical care, and access to treatment. The term itself, “SLE,” interferes with selecting appropriate lupus patients for participation in trials. Many people have moderate and even severe lupus syndromes who do not meet enough criteria to be labeled “SLE” (for example, immune thrombocytopenia, hemolytic anemia, discoid lupus, or subacute cutaneous lupus, which can cause severe rashes covering wide areas of the body). In this iteration, assigning less weight to cutaneous lupus as currently proposed is not just problematic, it will set the field back.

By not viewing cutaneous lupus as part of the lupus spectrum, we develop a false sense that this subset of people with lupus will not progress to “SLE,” yet many of them do. Even those who do not later develop features in other organs besides the skin may have more severe disease than other patients who do. Minimizing the “score” for cutaneous lupus will lead to individuals who carry a significant burden of disease being barred from trials, and from access to the treatments they need, once approved.

Conversely, people who do meet criteria for “SLE” under any algorithm, past or present, may have a range of severity, from very severe to very mild. The very mild patients (who may have, in their lifetime met the multiorgan criteria) are entering trials in large numbers and contributing to the high placebo responses which have stopped many promising investigational treatments from further development. Additionally, the common misuse of the current classification criteria as diagnostic criteria has become an unacceptable norm in the lupus community. This leads us to believe that new criteria will continue to be misused, further disenfranchising a huge segment of the population who have lupus from access to state-of-the-art research and care.

Advancing the development new classification criteria deserves a wider discussion among the field’s stakeholders, particularly those with expertise in clinical trial outcomes and the clinical care of the full spectrum of lupus patients.
 

Sandra C. Raymond is CEO and President, Leslie M. Hanrahan is VP of Education and Research, and Joan Merrill, MD, is the Chief Adviser for Clinical Development at the Lupus Foundation of America. Dr. Merrill is also the Oklahoma Medical Research Foundation Professor of Medicine at the University of Oklahoma, Oklahoma City.

Editor’s note: This commentary relates to the story, “New classification system for systemic lupus erythematosus moves forward.”

While work to develop a new set of lupus classification criteria more suitable for clinical research is important, the Lupus Foundation of America believes the current work is going in the wrong direction.

Increasingly, key opinion leaders understand lupus to be a spectrum of disease, and there is ample justification of this from scientific evidence (Nat Rev Rheumatol. 2015;11[7]:385-6) The criteria being worked on by ACR and EULAR draws upon an archaic concept with the musty name of “systemic lupus erythematosus,” which relies on a 19th century approach to categorizing disease by counting the signs and symptoms instead of by modern concepts of pathophysiology and prognostic severity. This imposes a homogeneity on the population that simply does not exist. Attempts to re-order obsolescent arrays of organs and autoantibodies to classify lupus will be futile, especially if the aim is to improve the rationale for clinical trial recruitment. Recent clinical trials and modern immunologic methods have already demonstrated, beyond a doubt, that subsets of patients, definable by gene expression patterns or state-of-the-art pharmacodynamic responses, do or do not respond to individual targeted treatments. We now know that patients who require different treatments may well share many of their symptoms in many of the same organs, and this fact defies the outmoded, abacus-based approach to disease classification.

We are concerned that redefining SLE by weighting all disease in one organ as more or less impactful than all disease in another organ flies in the face of current scientific knowledge. If this is the direction in which the effort is going, there is the potential for a negative impact on drug development, clinical care, and access to treatment. The term itself, “SLE,” interferes with selecting appropriate lupus patients for participation in trials. Many people have moderate and even severe lupus syndromes who do not meet enough criteria to be labeled “SLE” (for example, immune thrombocytopenia, hemolytic anemia, discoid lupus, or subacute cutaneous lupus, which can cause severe rashes covering wide areas of the body). In this iteration, assigning less weight to cutaneous lupus as currently proposed is not just problematic; it will set the field back.

By not viewing cutaneous lupus as part of the lupus spectrum, we develop a false sense that this subset of people with lupus will not progress to “SLE,” yet many of them do. Even those who do not later develop features in other organs besides the skin may have more severe disease than other patients who do. Minimizing the “score” for cutaneous lupus will lead to individuals who carry a significant burden of disease being barred from trials, and from access to the treatments they need, once approved.

Conversely, people who do meet criteria for “SLE” under any algorithm, past or present, may have a range of severity, from very severe to very mild. The very mild patients (who may have, in their lifetime, met the multiorgan criteria) are entering trials in large numbers and contributing to the high placebo responses which have stopped many promising investigational treatments from further development. Additionally, the common misuse of the current classification criteria as diagnostic criteria has become an unacceptable norm in the lupus community. This leads us to believe that new criteria will continue to be misused, further disenfranchising a huge segment of the population who have lupus from access to state-of-the-art research and care.

Advancing the development of new classification criteria deserves a wider discussion among the field’s stakeholders, particularly those with expertise in clinical trial outcomes and the clinical care of the full spectrum of lupus patients.
 

Sandra C. Raymond is CEO and President, Leslie M. Hanrahan is VP of Education and Research, and Joan Merrill, MD, is the Chief Adviser for Clinical Development at the Lupus Foundation of America. Dr. Merrill is also the Oklahoma Medical Research Foundation Professor of Medicine at the University of Oklahoma, Oklahoma City.

Editor’s note: This commentary relates to the story, “New classification system for systemic lupus erythematosus moves forward.”

While work to develop a new set of lupus classification criteria more suitable for clinical research is important, the Lupus Foundation of America believes the current work is going in the wrong direction.

Increasingly, key opinion leaders understand lupus to be a spectrum of disease, and there is ample justification of this from scientific evidence (Nat Rev Rheumatol. 2015;11[7]:385-6) The criteria being worked on by ACR and EULAR draws upon an archaic concept with the musty name of “systemic lupus erythematosus,” which relies on a 19th century approach to categorizing disease by counting the signs and symptoms instead of by modern concepts of pathophysiology and prognostic severity. This imposes a homogeneity on the population that simply does not exist. Attempts to re-order obsolescent arrays of organs and autoantibodies to classify lupus will be futile, especially if the aim is to improve the rationale for clinical trial recruitment. Recent clinical trials and modern immunologic methods have already demonstrated, beyond a doubt, that subsets of patients, definable by gene expression patterns or state-of-the-art pharmacodynamic responses, do or do not respond to individual targeted treatments. We now know that patients who require different treatments may well share many of their symptoms in many of the same organs, and this fact defies the outmoded, abacus-based approach to disease classification.

We are concerned that redefining SLE by weighting all disease in one organ as more or less impactful than all disease in another organ flies in the face of current scientific knowledge. If this is the direction in which the effort is going, there is the potential for a negative impact on drug development, clinical care, and access to treatment. The term itself, “SLE,” interferes with selecting appropriate lupus patients for participation in trials. Many people have moderate and even severe lupus syndromes who do not meet enough criteria to be labeled “SLE” (for example, immune thrombocytopenia, hemolytic anemia, discoid lupus, or subacute cutaneous lupus, which can cause severe rashes covering wide areas of the body). In this iteration, assigning less weight to cutaneous lupus as currently proposed is not just problematic; it will set the field back.

By not viewing cutaneous lupus as part of the lupus spectrum, we develop a false sense that this subset of people with lupus will not progress to “SLE,” yet many of them do. Even those who do not later develop features in other organs besides the skin may have more severe disease than other patients who do. Minimizing the “score” for cutaneous lupus will lead to individuals who carry a significant burden of disease being barred from trials, and from access to the treatments they need, once approved.

Conversely, people who do meet criteria for “SLE” under any algorithm, past or present, may have a range of severity, from very severe to very mild. The very mild patients (who may have, in their lifetime, met the multiorgan criteria) are entering trials in large numbers and contributing to the high placebo responses which have stopped many promising investigational treatments from further development. Additionally, the common misuse of the current classification criteria as diagnostic criteria has become an unacceptable norm in the lupus community. This leads us to believe that new criteria will continue to be misused, further disenfranchising a huge segment of the population who have lupus from access to state-of-the-art research and care.

Advancing the development of new classification criteria deserves a wider discussion among the field’s stakeholders, particularly those with expertise in clinical trial outcomes and the clinical care of the full spectrum of lupus patients.
 

Sandra C. Raymond is CEO and President, Leslie M. Hanrahan is VP of Education and Research, and Joan Merrill, MD, is the Chief Adviser for Clinical Development at the Lupus Foundation of America. Dr. Merrill is also the Oklahoma Medical Research Foundation Professor of Medicine at the University of Oklahoma, Oklahoma City.

Editor’s note: This commentary relates to the story, “New classification system for systemic lupus erythematosus moves forward.”

While work to develop a new set of lupus classification criteria more suitable for clinical research is important, the Lupus Foundation of America believes the current work is going in the wrong direction.

Increasingly, key opinion leaders understand lupus to be a spectrum of disease, and there is ample justification of this from scientific evidence (Nat Rev Rheumatol. 2015;11[7]:385-6) The criteria being worked on by ACR and EULAR draws upon an archaic concept with the musty name of “systemic lupus erythematosus,” which relies on a 19th century approach to categorizing disease by counting the signs and symptoms instead of by modern concepts of pathophysiology and prognostic severity. This imposes a homogeneity on the population that simply does not exist. Attempts to re-order obsolescent arrays of organs and autoantibodies to classify lupus will be futile, especially if the aim is to improve the rationale for clinical trial recruitment. Recent clinical trials and modern immunologic methods have already demonstrated, beyond a doubt, that subsets of patients, definable by gene expression patterns or state-of-the-art pharmacodynamic responses, do or do not respond to individual targeted treatments. We now know that patients who require different treatments may well share many of their symptoms in many of the same organs, and this fact defies the outmoded, abacus-based approach to disease classification.

We are concerned that redefining SLE by weighting all disease in one organ as more or less impactful than all disease in another organ flies in the face of current scientific knowledge. If this is the direction in which the effort is going, there is the potential for a negative impact on drug development, clinical care, and access to treatment. The term itself, “SLE,” interferes with selecting appropriate lupus patients for participation in trials. Many people have moderate and even severe lupus syndromes who do not meet enough criteria to be labeled “SLE” (for example, immune thrombocytopenia, hemolytic anemia, discoid lupus, or subacute cutaneous lupus, which can cause severe rashes covering wide areas of the body). In this iteration, assigning less weight to cutaneous lupus as currently proposed is not just problematic; it will set the field back.

By not viewing cutaneous lupus as part of the lupus spectrum, we develop a false sense that this subset of people with lupus will not progress to “SLE,” yet many of them do. Even those who do not later develop features in other organs besides the skin may have more severe disease than other patients who do. Minimizing the “score” for cutaneous lupus will lead to individuals who carry a significant burden of disease being barred from trials, and from access to the treatments they need, once approved.

Conversely, people who do meet criteria for “SLE” under any algorithm, past or present, may have a range of severity, from very severe to very mild. The very mild patients (who may have, in their lifetime, met the multiorgan criteria) are entering trials in large numbers and contributing to the high placebo responses which have stopped many promising investigational treatments from further development. Additionally, the common misuse of the current classification criteria as diagnostic criteria has become an unacceptable norm in the lupus community. This leads us to believe that new criteria will continue to be misused, further disenfranchising a huge segment of the population who have lupus from access to state-of-the-art research and care.

Advancing the development of new classification criteria deserves a wider discussion among the field’s stakeholders, particularly those with expertise in clinical trial outcomes and the clinical care of the full spectrum of lupus patients.
 

Sandra C. Raymond is CEO and President, Leslie M. Hanrahan is VP of Education and Research, and Joan Merrill, MD, is the Chief Adviser for Clinical Development at the Lupus Foundation of America. Dr. Merrill is also the Oklahoma Medical Research Foundation Professor of Medicine at the University of Oklahoma, Oklahoma City.