Fred was born July 1, 1936, in New York. He graduated from Queens College, N.Y., in 1958, and was a social worker for several years. He earned his medical degree in 1966 from the State University of New York, Downstate, Brooklyn, N.Y. He joined the U.S. Air Force in 1968 and was honorably discharged as a captain in 1970. He founded the Wichita Arthritis Center in 1974, and in 1979 became a clinical professor of internal medicine at the University of Kansas, Kansas City, Kan., eventually founding the Arthritis Research Center Foundation and the National Data Bank for Rheumatic Diseases.
Comments from Dr. Pincus
Fred was a remarkable person. He was driven by a passion to deliver better care and outcomes for his patients.
In the 1970s, he purchased a microcomputer as a tool for billing in his medical practice. He quickly realized that he could use the computer to also track his patients systematically, adding quantitative scores to traditional narrative descriptions. This practice enabled him to recognize whether patients were improving or worsening over long periods more accurately than relying on the memory of the doctor or patient.
Fred also recognized that he could use the computer information to analyze not only the courses of individual patients, but also the outcomes of groups of patients with different diagnoses to advance research concerning treatments and outcomes.
Fred applied these lessons to monitor his own patients—as well as patients of many other rheumatologists—by computer every three to six months, indefinitely. The data he collected ultimately encompassed thousands of patients from hundreds of care settings across the U.S., including several hundred of my patients. His database provided many important observations concerning the significance of patient questionnaires in the prognosis of severe outcomes of rheumatic diseases, such as work disability and premature mortality.1,2
In the 1980s, Fred began a productive collaboration with James F. Fries, MD, a pioneer in development of structured self-report questionnaires. He, Dr. Fries and collaborators recognized that carefully constructed patient questionnaires usually provided far more reproducible data than interviews by health professionals. He became a mainstay of the ARAMIS (Arthritis, Rheumatism and Aging Medical Information System) program at Stanford University, Palo Alto, Calif., supported by the National Institutes of Health for more than 20 years.
In 1985, Fred and Donna J. Hawley, MSN, EdD, reported that remission in rheumatoid arthritis was seen in less than 2% of patients, at a time when textbooks of rheumatology suggested that remission was common in the treatment of rheumatoid arthritis.3 He and Dr. Hawley recognized that short-term clinical trials and research studies over one year were often not translated into long-term care over 2–10 years.
Fred was the first to report that methotrexate, a new drug used to treat rheumatoid arthritis in the 1980s, was associated with this significant improvement in mortality outcomes, a major advance for rheumatology patients.4
He was also one of the first doctors to define criteria for fibromyalgia, endorsed by the ACR in 1990.
Fred produced hundreds of research papers on these topics and his research has been cited more than 125,000 times, according to Google Scholar.5 (For more information about Fred’s role in establishing the National Data Bank for Rheumatic Diseases, see our story.)
Fred was an unusually generous and collaborative person. Early in our friendship in the 1980s, a discussion about depression in rheumatoid arthritis led us to analyze his patient results, which indicated that responses to many items in the Minnesota Multiphasic Personality Inventory, interpreted as indicating hypochondriasis, hysteria and depression, were driven by expected responses of individuals with somatic diseases.6 We were co-authors of more than 45 published reports and a book in 1994 to introduce new concepts concerning rheumatoid arthritis.7
Fred co-authored publications with hundreds of rheumatologists, and shared his ideas, data and interpretations consistently over the years.
Comments from Dr. Michaud
“After I heard this bald and silver-bearded man yelling at the surgeon who cut your knee open and threw out what was inside, I knew you were in good hands!”
This remark from my grandmother about our initial encounter with Dr. Fred Wolfe in 1977—when he diagnosed me, a 3-year-old boy with a limp and swollen knee, with juvenile rheumatoid arthritis (JRA)—is one of many personal anecdotes from his distinctive and distinguished life.
He was first a rheumatologist: His notes showed genuine concern and thoughtfulness about his patients’ well-being, often hidden under a stern demeanor. He told me that after his two years in the Air Force that he wanted to stay in Wichita and found a spot by taking over a clinic for the sole rheumatologist. He said there was a lot less to learn back then.
He ran his private clinic for 30 years, from 1974 to 2004, and he collected electronic data on every patient he saw. I remember filling out a four-page questionnaire in the waiting area and watching one of his staff type everything into a computer in 30 seconds. When he saw me in the examination room, he had a dot matrix printout showing how my pain, physical function, gastrointestinal issues and more had changed during the past several visits. I just assumed this was standard practice, yet 40 years later I’ve learned how uncommon it still is now—and how very much ahead of his time Dr. Wolfe was.
In addition to computer software, Dr. Wolfe taught himself biostatistics. From SAS in the 1970s–90s to S+ and then Stata, R and WinBugs, there was always a new method to learn, a faster way to analyze the clinical data or a better graph to make. He jokingly mentioned that it was easier to publish papers using a brand-new statistical method because few understood enough to criticize. (Fred’s extensive vocabulary often had me digging into the largest dictionaries at the library for interpretation.)
I’m not sure at what moment the research bug hit, but Fred’s first publications echoed his vocal opinions, with letters to the editor calling out findings in JAMA in 1973, citing his own use of electronic medical records in 1977 and citing bias in 1982.8-10 Then, nine years after starting his clinic, he started publishing original research manuscripts—18 in his first two years. This led to more than 650 published papers and being listed in 2019 as one of the top 0.01% of all published scientists.11
He wrote to me about this: “A letter to me from John Ioannidis, one of my heroes. According to this ranking of citations I am in the 99.9th percentile of all scientists, alas beaten out by Tony Fauci and Steve Weinberg and, alas among rheumatologists, Dave Felson. We think this is all funny, but fun. Fred”
Fred conducted research in many areas, yet he is likely most known for his work with patient-reported outcome measures, patient registries and fibromyalgia criteria. By being a pioneer in collecting patient data early, he learned from and helped create more meaningful measures. He recognized the value of learning what the patient experienced at the clinic visit and away because he wanted to know what happened to his patients who didn’t return. This led to his involvement with the late Jim Fries’ ARAMIS registry and eventually to the creation of the National Data Bank for Rheumatic Diseases (NDB) in 1998, which paralleled national registries starting in Sweden and the U.K.
Some of his clinic patients had distinctive responses to questionnaires and were in distress. This led to his interest in fibromyalgia. While some saw his work as controversial in this area, he never wavered in why it was of such great interest; he knew these patients were suffering, and the lack of clear diagnoses, mechanisms of action or effective treatments meant there was more work to be done.
Hans Rasker, who had been a colleague of Fred’s since 1978, wrote to me, “Fred remained open minded, realizing the 1990 fibromyalgia criteria that he co-authored had methodological shortcomings; he noticed the opinion of the patients themselves were under-recognized. … The question, ‘What is pain?,’ how to define it and other aspects of fibromyalgia had his attention until his death.”
As Daniel Clauw, MD, professor of anesthesiology, psychiatry and rheumatology at the University of Michigan Medical School, recently stated, Fred truly was a “consummate physician-scientist and leader.”12 In between seeing patients, he would burst into my office with a new research idea or ask where I was with a figure. There was always something new to be done, spurred by listening to his patients.
His mind was never unoccupied. Yet it was not always about work. He had a love for modern art, classical music, reading and bicycling. On off-clinic days in 2002, he would blast classical music and air conduct phrases and tell us something unique about the composer or recording. In his later years, he focused on photography, gardening and cooking. He had great pride in his sons and grandkids and loved to brag about them even when distance kept them apart.
Fred had so many stories to share. From childhood I can still imagine him in the back of a classroom answering the teacher’s “Who knows …” question with a low booming, “The Shadow Knows” and subsequently getting detention. I can see him “trading” patients with other New York City medical schools to learn about more interesting cases. I’ve heard his stories about John Tukey and Richard Feynman, and I started to wonder if this brilliant and bullheaded Brooklyn Jew may have felt a bit isolated in the Great Plains. Yet unlike these other scientific greats, he avoided conventional academia arguably to maintain his version of independent and productive research.
An aspect of academia I suspect Fred missed was having a formal system for mentorship. He was eager to help any student or physician anywhere and anytime. He co-led the CHORD rheumatology fellowship from 2003-2006, which provided research training and funding for 45 fellows. He took a chance on me, someone without any formal statistics training but eager to learn, to be his statistician in 2001. Even in his final days in the intensive care unit he was providing research support to those who asked.
I last saw Fred in June when making my annual visit to his home with my family. He was throwing tennis balls into the deep end of the pool for Chester, the family golden retriever, to get while my kids and I acted as obstacles in Chester’s way. Fred made us a great meal, had lots of smiles and we talked easily and often. Most visits Fred had “one more paper” he was working on to tell me about, but this time one didn’t come to mind. We just enjoyed the moment together, former patient and physician, mentee and mentor, and good friends.
An Active Life
Fred was an enthusiastic cyclist and, as a member of the Oz Bicycle Club, he participated in Biking Across Kansas many times. He also rode over the Continental Divide and toured several states. He had many passions, including amateur radio, opera, cooking and gardening.
Fred was a giant, a unique combination of unbridled altruism and brilliant computer skills. He never stopped being a social worker, driven to develop better patient care to the exclusion of personal advancement and financial gain. His contributions resound throughout the world, and he will be sorely missed by patients and the community of rheumatologists to whom he contributed so many advances.
Fred is survived by his wife, Donna Hawley; his sister, Susan Sanders and her husband, Fredric Sanders; his children, Aaron Wolfe, Ezra Wolfe and David Wolfe; daughters-in-law, Terrilyn McCormick and Erica Wolfe; and five grandchildren, Cy Wolfe, Allison Wolfe, Oscar Wolfe, Amos Wolfe and Lennard Wolfe.
Theodore Pincus, MD, is a professor of medicine in the Division of Rheumatology, Rush University Medical Center, Chicago.
Kaleb Michaud, PhD, is a professor in the Division of Rheumatology and Immunology, University of Nebraska Medical Center, and the director of FORWARD, The National Databank for Rheumatic Diseases.
- Wolfe F, Pincus T. Listening to the patient: A practical guide to self-report questionnaires in clinical care. Arthritis Rheum. 1999 Sep;42(9):1797–1808.
- Wolfe F, Pincus T. Standard self-report questionnaires in routine clinical and research practice—an opportunity for patients and rheumatologists. J Rheumatol. 1991 May;18(5):643–646.
- Wolfe F, Hawley DJ. Remission in rheumatoid arthritis. J Rheumatol. 1985 Apr;12(2):245–252.
- Choi HK, Hernán MA, Seeger JD, Robins JM, Wolfe F. Methotrexate and mortality in patients with rheumatoid arthritis: A prospective study. Lancet. 2002 Apr 6;359(9313):1173–1177.
- Frederick Wolfe, M.D. Google Scholar. 2023 Oct 2.
- Pincus T, Callahan LF, Bradley LA, Vaughn WK, Wolfe F. Elevated MMPI scores for hypochondriasis, depression, and hysteria in patients with rheumatoid arthritis reflect disease rather than psychological status. Arthritis Rheum. 1986 Dec;29(12):1456–1466.
- Wolfe F, Pincus T. Rheumatoid Arthritis: Pathogenesis, Assessment. Outcome, and Treatment. New York: Marcel Dekker; 1994.
- Wolfe F. SLE latex test kit. JAMA. 1973 Oct 15;226(3):357.
- Wolfe F, Norris WL, Wilber M. ARA standard database reconsidered. Arthritis Rheum. 1977 Nov–Dec;20(8):1556.
- Wolfe F. Selection bias in fibrositis study. Arthritis Rheum. 1982 Nov;25(11):1390.
- Ioannidis JPA, Boyack KW, Baas J. Updated science-wide author databases of standardized citation indicators. PLoS Biol. 2020 Oct 16;18(10): e3000918.
- Martin E. Celebrating the life of Frederick Wolfe, MD: ‘The consummate physician-scientist.’ Healio Rheumatology. 2023 Sep 15.