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Overdiagnosis and overtreatment in rheumatology: a little caution is in order
  1. Robert B M Landewé1,2
  1. 1 Rheumatology & clinical immunology, Amsterdam Rheumatology Center, Amsterdam, The Netherlands
  2. 2 Rheumatology, Zuyderland Medical Center, Heerlen, The Netherlands
  1. Correspondence to Professor Robert B M Landewé, Amsterdam Rheumatology and Clinical Immunology Center, Amsterdam and Zuyderland Medical Center, Amsterdam 1105 AZ, The Netherlands; landewe{at}


Overdiagnosis is a term coined by experts in cancer screening to point to indolent cancers detected by screening that would have never led to manifest health problems. Overdiagnosis leads to unnecessary medical care (overtreatment), anxiety and cost. In rheumatology overdiagnosis and overtreatment are hardly discussed but likely present. This viewpoint examines how our prevailing views on the management of inflammatory rheumatic diseases may relate to overdiagnosis and overtreatment. Six paradigms of modern rheumatology will be discussed: early diagnosis, intensive treatment, remission, prognosis and risk stratification, evidence-based rheumatology, and precision medicine. It is concluded that, in spite of the enormous progress that they have brought, all paradigms bear the intrinsic dangers of overdiagnosis and overtreatment. So a little caution is in order.

  • early rheumatoid arthritis
  • patient perspective
  • psoriatic arthritis
  • spondyloarthritis
  • treatment

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Overdiagnosis, a term coined by experts in cancer screening, is an unwarranted side effect of screening.1 It points to cancers detected by screening that—if remain undiagnosed—will never lead to manifest health problems because of their indolent character. Overdiagnosis leads to overtreatment (unnecessary healthcare), psychological distress and huge costs.

While overdiagnosis and overtreatment show up everywhere in medicine,2 there is remarkably little scientific attention. GB Welch3 explained overdiagnosis and overtreatment as inherent consequences of medical doctors’ attitude: ‘Doctors attempt to mitigate a risk without considering how small or unlikely the potential benefit is, they try to fix a problem rather than monitor and cope with it, they prefer to act quickly rather than waiting for more information, and they prefer newer treatments over older’ (sic). The influence of the public on their attitude should not be underestimated.

Overdiagnosis and overtreatment in rheumatology

For inflammatory rheumatic diseases, such as rheumatoid arthritis (RA), psoriatic arthritis (PsA) and ankylosing spondylitis (AS), the story of overdiagnosis and overtreatment is a tabula rasa. That is understandable. After a long history of therapeutic nihilism and acquiescence, the focus in rheumatology has shifted from caring for the disabled to actively finding the unrecognised, from a wait-and-see policy to early intervention, and from careful step-up treatment with poorly effective but toxic drugs to immediate intervention with powerful new drug combinations. To date, no one seems to bother about overdiagnosis and overtreatment since for the first time in history we have an opulence of effective drugs and more are coming. Critical questions about early diagnosis and treatment are no-brainers, since ‘early’ implies ‘before irreversible damage has occurred’, and isn’t that at everybody’s benefit? In addition, it is a fact of life that in many countries getting proper access to ‘necessary health care’ is still a more urgent problem than dealing with ‘unnecessary health care’.

In cancer, early detection has always intuitively implied better prognosis, but this faith has recently been shaken. In some patients early detection has indeed saved lives, but in others an early cancer diagnosis has initiated an unnecessary chain of harms: they received a burdening diagnosis of cancer, but this cancer would have never impacted their lives if they had stayed ignorant.3 Cancer screening advocates still consider this collateral damage of a greater good.

Inflammatory rheumatic diseases differ from cancer in many aspects, and overdiagnosis and overtreatment will take another shape, but there are peculiar similarities too. In this Viewpoint article I shall examine our current rather offensive approach to detect and treat inflammatory diseases against the potential hazards of overdiagnosis and overtreatment. I will do this by discussing six popular paradigms illustrative of our current vision. These six discussions reflect my personal opinion and are not (yet) underpinned by scientific data from the literature. To fully appreciate these issues, however, additional studies are required.

Paradigm 1: early diagnosis

A clinical diagnosis of an inflammatory rheumatic disease is the prerogative of the skilled rheumatologist. There is no proper alternative. Objective tests do not suffice for a diagnosis and a rheumatic disease may still exist in the absence of objective evidence. The quest to an earlier diagnosis therefore demanded a lot from the practising rheumatologist. Several initiatives have been taken to convince the rheumatologist of the relevance of early diagnosis: early arthritis and back pain clinics, referral criteria for general practitioners, new sophisticated imaging, smarter diagnostic tests, and on top of that a thorough rethinking of the classification criteria. Some have been recently reformulated to serve the demand for an earlier diagnosis better,4–6 although we know that diagnosis and classification are distinct entities that can easily be muddled up.7

These initiatives may have had double-faced effects. Bad cases may have reached the office of the rheumatologist timelier, but in their wake many milder cases with less clear symptoms and a better prognosis will have shown up too. New diagnostic tests (eg, ultrasound) that promised increased sensitivity may have contributed to a considerable rise in incidence. More inclusive classification criteria, inappropriately used to diagnose more patients, may have stretched the disease spectrum further. The net result is more ‘grey-zone medicine’ with milder patients diagnosed earlier than before, prepared for our intensive treatments.

We have even gone beyond the limits of early diagnosis. Recent research aims at identifying risk groups of patients with a propensity to develop true inflammatory disease (eg, clinically suspect arthralgia8) in order to treat them pre-emptively. This is befuddling risk of disease with presence of disease, which may turn healthy people into patients and can cause collateral damage.

Paradigm 2: intensive treatment

It is beyond any doubt that the discovery and implementation of many new treatments during the last two decades have had a tremendous positive influence. The intensive treatment paradigm, when evaluated against the background of treatment results before 1990, has markedly improved the outcome of patients with classic RA, PsA and AS. Early diagnosis and intensive treatment have gone hand in hand. This response to the submissive ‘go-low-go-slow’ movement was welcomed and spearheaded by the successes of—among others—the COBRA trial in RA9 and later on the BeST trial.10 The surge of new effective medicines and innovative therapeutic strategies that has followed was justified by improving the outcomes in the most severe and active patients in trials. However, trial results are average group results that do not unveil that clinical superiority is often caused by only a minority in the trial. The majority could have done similarly well on usual therapy. The type of overtreatment that follows from this principle has apparently been broadly accepted in the medical community: ‘Some need it some do not’.2 This may be a justifiable approach if there is no alternative, but modern rheumatology has been gifted with an ample choice of very effective drugs. Only their hierarchical priority across the spectrum of disease has been poorly studied. To date, we still extrapolate trial results obtained in severe patients to those with milder disease, convinced that we do a good job, but we likely overtreat some of them.

Paradigm 3: remission

The paradigm that clinical remission is the best achievement for patients and doctors is a strong one, but one that easily leads to overtreatment in many patients. The paradigm of remission is based on the proven relationship between clinical disease activity and structural damage progression across inflammatory diseases11 12: ‘the lower the disease activity the better the outcome’.

Admittedly, our belief in the virtues of clinical remission may be correct from the perspective of the patient with severe disease and high disease activity. However, the marginal effect of ‘pushing toward remission’ in a patient already in a low disease activity state may be of negligible value in some cases and may do more harm than good. Strategy trials may have proven the feasibility of intensive monitoring and treat-to-remission, but their surplus efficacy on radiographic progression was minimal or absent.13–15 The question if the difference between zero and minimal structural progression really adds value to the patients, given the totality of factors that contribute to ‘happy patients’,16 has not been answered by these trials. What we have learnt, though, is that drug use in patients who were intensively monitored and steered towards remission was markedly higher than in patients treated regularly—a subtle sign of overtreatment.

Paradigm 4: prognosis and risk stratification

Many publications have dealt with prognosis of outcome or prediction of treatment response. Imaging tests, biomarkers and translational ‘signatures’ have all been investigated for their prognostic potential. Most of them were not reproducible. If they were, their marginal effects over and above simple clinical measurements were, if tested at all, negligible and not clinically relevant.17 Prognostic research is difficult in the absence of untreated patients that show the natural course of the disease. Unfortunately, many researchers, clinicians and the public are not appropriately educated to interpret prognostic (risk) information and grossly overestimate its value. We still do not know about the most important health outcomes to patients, namely those outcomes that truly add value and that we should actually be able to predict.16 Diagnosis and treatment based on unreliable prognostic markers will inevitably lead to overdiagnosis and overtreatment in a number of patients.

Paradigm 5: evidence-based rheumatology

Randomised clinical trials form the major source for evidence-based medicine (EBM). The field has made marked progress by systematising the culminating evidence into clinical guidelines (recommendations).18–20 Systematic literature review and expert judgement of the evidence are at the basis of the guidelines, which intend to describe the state of the art and to help clinicians making treatment decisions in individual patients. Undoubtedly, guidelines are an asset to clinicians for many reasons, but are not always well understood and properly used. Guidelines reflect, in principle, the consensual opinion of medical experts regarding the available evidence in the literature and describe best-practice irrespective of the local situation of patients, healthcare systems and countries. Guidelines also breathe prevailing visions in the field, such as early diagnosis and intensive treatment towards remission. In addition, guidelines may have legislative and economical implications and can lead to defensive medicine. Sometimes, and alien to the intentions of the EBM movement, guidelines are too rigidly pursued by clinicians who may ignore the needs of individual patients. Such a practice may contribute to overdiagnosis and overtreatment.

Paradigm 6: precision medicine

Precision medicine is a current hype, boosted by former President Obama’s Precision Medicine Initiative from 2016.21 Precision medicine suggests that patients with a particular diagnosis can be separated into subgroups based on genetic, cellular or molecular analysis, each with a special medical intervention. Advocates of precision medicine claim that current drug treatments, although effective in drug trials, fall short because so many of our patients do not reach remission or lose efficacy over time. While precision medicine appeals to the public and to funding bodies, because it breathes technological innovation, influential critics have warned that precision medicine will not lead to increased patient values and may cause overdiagnosis, overtreatment and cost explosions.22 Even if precision medicine will succeed in elucidating and targeting multiple pathways of the same disease, the ultimate treatment success will not only depend on cellular and biological factors but rather on an intangible interplay of comorbidities, psychosocial factors, compliance, beliefs and non-scientific perceptions. In other words, while it is unlikely that precision medicine will eventually become the holy grail of rheumatology, it may have caused already a lot of unnecessary medicine far before we have realised.

In summary, all prevailing paradigms of disease management bear—in my opinion—the potential risk of overdiagnosis and overtreatment. This appreciation does not intend to disavow the immense progress that has been made, on the contrary. It argues in favour of a more frugal and sustainable vision on how to best manage our inflammatory rheumatic diseases in the future, now that we have such a broad spectrum of effective drugs and strategies available. We may have to acknowledge in rheumatology that ‘earlier’ (diagnosis) is not always necessarily ‘better’, that ‘more’ (treatment) is not automatically ‘more effective’, and that ‘increased sensitivity’ (of diagnostic tests) is not synonymous to ‘better yield’. We need to better distinguish ‘disease’ from the ‘risk of disease’. We need trials investigating how to best manage all those milder cases that come to us as a result of our early diagnosis initiatives. We need to learn what does and does not really matter to patients with inflammatory rheumatic diseases.16 We need to pay more attention to possible overdiagnosis and overtreatment in our clinical research. And we need to learn, without relinquishing all the good of early intensive interventions and our precious new treatments, how we can further increase the value of our healthcare for the sake of our patients with inflammatory rheumatic diseases and for society that has to pay the bill.

A little caution is in order.


View Abstract


  • Handling editor Josef S Smolen

  • Contributors The author is fully responsible for the content of this manuscript, for drafting it, revising it and approving it for publication.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Patient consent Not required.

  • Provenance and peer review Not commissioned; externally peer reviewed.