Clinical Therapeutics/Volume ], Number ], 2014
Editor-in Chief’s Note Rheumatoid Arthritis and More Imagine a pyramid flipped and standing on its head or apex—a complete reversal of a traditional image. Agents such as methotrexate and the more recently introduced biologics have been altering the traditional paradigm for the treatment of rheumatoid arthritis for the last 30 or so years. And since the advent of the newer biologics, the rate of change has accelerated. I clearly recall the gnarly, ulnar deviated hands of patients I saw in rheumatology clinic in the late 1950s. We followed a treatment paradigm aimed solely at producing relief of pain and discomfort. The idea of halting or reversing disease progression was not part of the picture—there were no “magic bullets” or pills. For patients who had not progressed very far, we were taught to start conservatively—exercise by squeezing a tennis ball, warm soaks, and aspirin. Prednisone was the next step; it had just been introduced in 1955. Other nonsteroidal antiinflammatory Richard I. Shader, MD agents, such as ibuprofen, did not become available until the 1960s. More powerful and potentially disease-modifying agents (DMARDs), such as methotrexate (both oral and parenteral) and oral gold, were not approved until almost the last decade of the 20th century. Even with the availability of these and other early DMARDs, the paradigm remained the same until very recently—start with the most benign agents and wait a few years before using DMARDs—even though progressive joint destruction was still taking place. With the emergence of new biologics and better use of corticosteroids, the picture is changing and the paradigm is gradually flipping. Remembering my clinic experiences, and in light of the introduction of a generation of disease modifying biologics, the words of this poem formed in my mind: These fingers Once flexible We’ve taken for granted. Now stiffened And swollen They’re looking quite slanted. Pain filled days And anger, We’ve complained even ranted. Then relief From a pill That seems almost enchanted. DMARD biologics such as adalimumab,* etanercept,† infliximab,‡ and others, all require parenteral administration. Tofacitinib§ is the first new oral agent. Because all of the agents are relatively quick in their *
Trademark: Trademark: ‡ Trademark: § Trademark: †
] 2014
Humiras (AbbVie Inc, Lake Bluff, Illinois). Enbrels (Amgen, Thousand Oaks, California). Remicades (Janssen, Titusville, New Jersey). Xeljanz (Pfizer, New York, New York).
1
Clinical Therapeutics onset and all can halt progressive damage to joints, the obvious question is: Why are they not first-line therapy? Why hasn’t the paradigm been completely flipped? The answer is well known to those who have seen the plethora of direct-to-consumer television ads. All of these agents lower the threshold to serious infections, such as tuberculosis. Yet, perhaps partly because of these direct-to-consumer ads, adalinumab, etanercept, and infliximab were among the top 10 best selling drugs in the United States from April 2013 through mid-March, 2014.1 Together they accounted for just over $15 billion in sales in that 1-year interval. Clearly, the search for safer, and perhaps cheaper, treatments for rheumatoid arthritis will and must go on. In this issue, we are taking a break from our themed Updates, just as we did last summer. Some of you might be aware that we published very few papers related to rheumatic diseases in 2013. As a result, in 2014 we ended any dedicated coverage of this topic. However, when the European League Against Rheumatism (EULAR) promulgated new guidelines for the treatment of rheumatoid arthritis, I asked Dr Eugene Kissin, our former Topic Editor for this focus area, to write a Commentary about them. He has done so2 and, by coincidence, several other complementary papers were also submitted.3–5 Hence, we are publishing them as a group. The Clinical Therapeutics publishing team wishes you a happy summer—and for our friends below the Equator, a happy and tolerable winter. Richard I. Shader, MD Editor-in-Chief
REFERENCES 1. Brooks, M. The 100 most prescribed, top selling drugs. May 13, 2014. Available at: http://www.medscape.com/viewarticle/ 825053. Accessed May 30, 2014. 2. Kissin E. Our “Dirty” Little Secret Exposed in the 2013 EULAR Recommendations for Rheumatoid Arthritis. Clin Ther. 2014;36. XXX-XXX. 3. Kaur K, Kalra S, Kaushal S. Systematic Review of Tofacitinib: a new drug for management of rheumatoid arthritis. Clin Ther. 2014;36. XXX-XXX. 4. Curtis JR, Schabert VF, Harrison DJ, Yeaw J, Korn JR, Quach C, Yun H, Joseph GJ, Collier DH. Estimating effectiveness and cost of biologics for rheumatoid arthritis: application of a validated algorithm to commercial insurance claims. Clin Ther. 2014;36. XXX-XXX. 5. Dhir V, Singla M, Gupta N, Goyal P, Sagar V, Sharma A, Khanna S, Singh S. Randomized Controlled Trial Comparing Two Different Starting Doses of Methotrexate in Rheumatoid Arthritis. Clin Ther. 2014;36. XXX-XXX.
http://dx.doi.org/10.1016/j.clinthera.2014.06.017
2
Volume ] Number ]
Editor-in Chief’s Note Rheumatoid Arthritis and More Imagine a pyramid flipped and standing on its head or apex—a complete reversal of a traditional image. Agents such as methotrexate and the more recently introduced biologics have been altering the traditional paradigm for the treatment of rheumatoid arthritis for the last 30 or so years. And since the advent of the newer biologics, the rate of change has accelerated. I clearly recall the gnarly, ulnar deviated hands of patients I saw in rheumatology clinic in the late 1950s. We followed a treatment paradigm aimed solely at producing relief of pain and discomfort. The idea of halting or reversing disease progression was not part of the picture—there were no “magic bullets” or pills. For patients who had not progressed very far, we were taught to start conservatively—exercise by squeezing a tennis ball, warm soaks, and aspirin. Prednisone was the next step; it had just been introduced in 1955. Other nonsteroidal antiinflammatory Richard I. Shader, MD agents, such as ibuprofen, did not become available until the 1960s. More powerful and potentially disease-modifying agents (DMARDs), such as methotrexate (both oral and parenteral) and oral gold, were not approved until almost the last decade of the 20th century. Even with the availability of these and other early DMARDs, the paradigm remained the same until very recently—start with the most benign agents and wait a few years before using DMARDs—even though progressive joint destruction was still taking place. With the emergence of new biologics and better use of corticosteroids, the picture is changing and the paradigm is gradually flipping. Remembering my clinic experiences, and in light of the introduction of a generation of disease modifying biologics, the words of this poem formed in my mind: These fingers Once flexible We’ve taken for granted. Now stiffened And swollen They’re looking quite slanted. Pain filled days And anger, We’ve complained even ranted. Then relief From a pill That seems almost enchanted. DMARD biologics such as adalimumab,* etanercept,† infliximab,‡ and others, all require parenteral administration. Tofacitinib§ is the first new oral agent. Because all of the agents are relatively quick in their *
Trademark: Trademark: ‡ Trademark: § Trademark: †
] 2014
Humiras (AbbVie Inc, Lake Bluff, Illinois). Enbrels (Amgen, Thousand Oaks, California). Remicades (Janssen, Titusville, New Jersey). Xeljanz (Pfizer, New York, New York).
1
Clinical Therapeutics onset and all can halt progressive damage to joints, the obvious question is: Why are they not first-line therapy? Why hasn’t the paradigm been completely flipped? The answer is well known to those who have seen the plethora of direct-to-consumer television ads. All of these agents lower the threshold to serious infections, such as tuberculosis. Yet, perhaps partly because of these direct-to-consumer ads, adalinumab, etanercept, and infliximab were among the top 10 best selling drugs in the United States from April 2013 through mid-March, 2014.1 Together they accounted for just over $15 billion in sales in that 1-year interval. Clearly, the search for safer, and perhaps cheaper, treatments for rheumatoid arthritis will and must go on. In this issue, we are taking a break from our themed Updates, just as we did last summer. Some of you might be aware that we published very few papers related to rheumatic diseases in 2013. As a result, in 2014 we ended any dedicated coverage of this topic. However, when the European League Against Rheumatism (EULAR) promulgated new guidelines for the treatment of rheumatoid arthritis, I asked Dr Eugene Kissin, our former Topic Editor for this focus area, to write a Commentary about them. He has done so2 and, by coincidence, several other complementary papers were also submitted.3–5 Hence, we are publishing them as a group. The Clinical Therapeutics publishing team wishes you a happy summer—and for our friends below the Equator, a happy and tolerable winter. Richard I. Shader, MD Editor-in-Chief
REFERENCES 1. Brooks, M. The 100 most prescribed, top selling drugs. May 13, 2014. Available at: http://www.medscape.com/viewarticle/ 825053. Accessed May 30, 2014. 2. Kissin E. Our “Dirty” Little Secret Exposed in the 2013 EULAR Recommendations for Rheumatoid Arthritis. Clin Ther. 2014;36. XXX-XXX. 3. Kaur K, Kalra S, Kaushal S. Systematic Review of Tofacitinib: a new drug for management of rheumatoid arthritis. Clin Ther. 2014;36. XXX-XXX. 4. Curtis JR, Schabert VF, Harrison DJ, Yeaw J, Korn JR, Quach C, Yun H, Joseph GJ, Collier DH. Estimating effectiveness and cost of biologics for rheumatoid arthritis: application of a validated algorithm to commercial insurance claims. Clin Ther. 2014;36. XXX-XXX. 5. Dhir V, Singla M, Gupta N, Goyal P, Sagar V, Sharma A, Khanna S, Singh S. Randomized Controlled Trial Comparing Two Different Starting Doses of Methotrexate in Rheumatoid Arthritis. Clin Ther. 2014;36. XXX-XXX.
http://dx.doi.org/10.1016/j.clinthera.2014.06.017
2
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