Clinical inertia in rheumatology practice

Introduction

Rheumatic diseases include several autoimmune inflammatory diseases such as rheumatoid arthritis (RA), psoriatic arthritis, spondyloarthropathies (SpA), Lupus, scleroderma and myositis, in addition to diseases such as osteoporosis, fibromyalgia, gout and osteoarthritis. These diseases are common in our society, but there are lingering concerns about whether they are being treated appropriately and in time. Available evidence suggests that there is a delay in diagnosing and treating various rheumatic diseases.^1,2 In this perspective, we discuss clinical inertia in the management of autoimmune rheumatic diseases as one of the major factors responsible for this delay and propose ways to overcome this. Though we have used several specific examples of RA, the principles are also applicable to other autoimmune rheumatic diseases.

Clinical inertia is defined as ‘failure of healthcare providers to initiate or intensify therapy when indicated’.³ Recognising clinical inertia is easy in the case of a disease where there is a well-defined treatment target value. For this reason, clinical inertia resulting in an inability to attain treatment targets has been well described in chronic diseases such as diabetes mellitus (DM), hypertension and dyslipidaemia.^4,5,6,7 In contrast, in multiple sclerosis, a disease with flare and remission, clinical inertia is defined as ‘lack of treatment initiation or escalation when there is evidence of disease activity’.⁸ Several rheumatic diseases also follow a course of relapses and remissions.

Some researchers divide clinical inertia into two broad categories – diagnostic inertia and therapeutic inertia – to account for both aspects. Based on previous discussion, we can define clinical inertia in rheumatic diseases as inability or undue delay to diagnose rheumatic diseases, initiate or intensify (escalate) therapy when the disease is active or de-escalate therapy when the disease is under remission. To understand clinical inertia in the context of rheumatic diseases, there should be clearly defined criteria and measurable parameters for disease activity to make early diagnosis and initiate and optimise treatment. Understanding the various factors contributing to clinical inertia is helpful in ensuring appropriate planning to tackle the issue (Table 1).

Inertia in diagnosis

Early diagnosis of rheumatic diseases is hugely important for starting proper therapy and achieving a favourable prognosis.⁹ For example, in patients with RA, treatment must be initiated within 12 weeks from the onset of symptoms, which is described as the ‘therapeutic window of opportunity’.¹⁰ Early diagnosis and prompt treatment are important predictive factors for achieving remission in RA.¹¹ Diagnostic delays in other rheumatic diseases such as spondyloarthropathies and Lupus vary from months to years; more than 10 years in the former and as long as 30 months in the latter.^12,13

Some of the factors that contribute to a delay in diagnosis are delayed presentation, varying clinical picture, lack of time in busy outpatient departments for proper evaluation, lack of relevant expertise of healthcare providers, low awareness among patients leading to ignoring early symptoms, delay in referral from the primary care facility, symptomatic improvement with analgesics, and lack of laboratory facilities to test inflammatory and autoimmune markers. Atypical presentations and a negative laboratory report for immunological markers contribute to delay in diagnosis even in secondary and tertiary care levels. Diagnostic delay among seronegative RA patients compared with those with seropositive RA is a classic example of this.¹⁴

Inertia in initiating DMARDs

Early and aggressive therapy improves the outcome and helps in achieving remission in many autoimmune rheumatic diseases such as RA. Even though early initiation of conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) is included in all treatment guidelines, there is often a significant delay.^15,16 Non-steroidal anti-inflammatory drugs (NSAIDs) and glucocorticoids act fast and reduce joint pain and stiffness. This symptomatic relief contributes to the delay in initiating treatment with DMARDs. Initiation and up-titration of DMARDs depend on various factors such as disease activity and severity, associated comorbidities and patient preference. Drug-specific factors such as cost, route of administration, adverse effects and frequency of monitoring can also contribute to clinical inertia in some healthcare settings.

It has also been reported that women of childbearing age with rheumatic diseases commonly receive suboptimal management and inappropriately discontinue treatment.¹⁷ Lack of data means that the safety and potential risk of teratogenicity of available therapies are the main concerns during pregnancy and lactation, though there has been a rapid increase in our knowledge in recent years.¹⁸

Inertia in initiating biological DMARDs

In addition to cost, several other factors may contribute to clinical inertia in using various biological DMARDs in patients with rheumatic diseases, including the inconvenience of having injections, infusions requiring hospital visits, fear of infections and reactivation of latent tuberculosis. Failure to initiate these agents when there is severe disease or when conventional DMARDs have not been able to control disease activity often leads to poorer outcomes and reduces the chance of remission.

Inertia in modifying treatment

After starting DMARDs in patients with rheumatic diseases, further management depends upon the response and adverse effects, requiring either escalation (intensification) of therapy or de-escalation of therapy.

Escalation

In patients on DMARDs with persistent active disease, escalation of therapy is ideally indicated at the earliest opportunity to prevent organ damage and to achieve disease remission. However, in the real world there is considerable delay in this.

De-escalation

Similarly, de-escalation must be considered in patients who have achieved sustained disease remission, but this is also often delayed. Another reason to consider de-escalation is to minimise drug toxicities by reducing exposure.

Inertia in monitoring

Patients with rheumatic diseases require frequent clinical and laboratory monitoring to assess disease activity and drug-related adverse effects at specified intervals. This crucial aspect is often delayed due to many factors including financial constraints, which also contribute to clinical inertia (Table 1).

Table 1 Factors contributing to clinical inertia in people with rheumatic diseases

Inertia in addressing comorbidities

Associated comorbidities such as hypertension, diabetes and cardiovascular diseases also need to be addressed properly. Cardiovascular disease remains a major cause of mortality in patients with RA and Lupus.^19,20 In an international audit involving 19 countries of the management of dyslipidaemia and hypertension in patients with RA, it was noted that the lipid target attainment was only 45% and 18% in the high and very high risk groups respectively and 62% had hypertension, but only approximately half of these patients were attaining target blood pressure.²¹ In another study, atherosclerotic cardiovascular disease (ASCVD) was present in 26.7% of patients with RA and DM, compared with 11.6% without DM, indicating the need for effective control of risk factors.²² Inertia in controlling these risk factors and providing adequate screening for cardiovascular illness results in poorer outcomes.

How to tackle clinical inertia

Treat to target (T2T) in rheumatic diseases is used mainly to achieve disease remission. Any delay in diagnosis or in initiation and intensification of therapy can result in permanent organ damage and reduces the chance of remission. Clinical inertia due to various causes contributes to failure in achieving T2T goals. Addressing clinical inertia helps to overcome this.

Addressing factors contributing to clinical inertia, whether they are related to the patient, physician or system, may help in overcoming what is referred to as ‘treatment failure’. Factors that help overcome clinical inertia include educating the public and patients about rheumatic diseases, updating and training healthcare providers on various aspects of treatment, providing specialist support, adopting a multidisciplinary team approach, and improving healthcare facilities (Table 2).

Table 2 Steps to tackle clinical inertia

Conclusion
Clinical inertia is common in all chronic non-communicable diseases and it is multi-factorial, with contributory elements from all stakeholders including healthcare set-ups and providers, patients and their caregivers. Before labelling management of rheumatic disease in an individual as a ‘failure’, careful consideration of relevant factors linked to clinical inertia may be helpful. 

References

1. Raciborski F, Kłak A, Kwiatkowska B et al. Diagnostic delays in rheumatic diseases with associated arthritis. Reumatologia 2017; 55: 169–176.
2. Harrold LR, Reed GW, Kremer JM et al. Identifying factors associated with concordance with the American College of Rheumatology rheumatoid arthritis treatment recommendations. Arthritis Res Ther 2016; 18: 94.
3. Phillips LS, Branch WT, Cook CB et al. Clinical inertia. Ann Intern Med 2001; 135: 825–34.
4. Strain WD, Bluher M, Paldanius P. Clinical inertia in individualising care for diabetes: is there time to do more in type 2 diabetes? Diabetes Ther 2014; 5: 347–54.
5. Raveendran AV. Understanding clinical inertia in diabetes. J Soc Health Diabetes 2019; 7. doi: 10.1055/s-0039-1694300.
6. Reach G. Clinical inertia, uncertainty and individualized guidelines. Diabetes Metab 2014; 40: 241–5.
7. Rodondi N, Peng T, Karter AJ et al. Therapy modifications in response to poorly controlled hypertension, dyslipidemia, and diabetes mellitus. Ann Intern Med 2006; 144: 475–84.
8. Saposnik G, Sempere AP, Prefasi D et al. Decision-making in multiple sclerosis: the role of aversion to ambiguity for therapeutic inertia among neurologists (DIScUTIR MS). Front Neurol 2017; 8: 65.
9. Van Eijk IC, Nielen MMJ, Van der Horst-Bruinsma I et al. Aggressive therapy in patients with early arthritis results in similar outcome compared with conventional care: the STREAM randomized trial. Rheumatology (Oxford) 2012; 51: 686–694.
10. Smolen JS, Landewé R, Bijlsma J et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2016 update. Ann Rheum Dis 2017; 76: 960–977.
11. Gremese E, Salaffi F, Bosello SL et al. Very early rheumatoid arthritis as a predictor of remission: a multicentre real life prospective study. Ann Rheum Dis 2013; 22: 858–862.
12. Feldtkeller E, Khan MA, van der Heijde D et al. Age at disease onset and diagnosis delay in HLA-B27 negative vs. positive patients with ankylosing spondylitis. Rheumatol Int 2003; 23: 61–66.
13. Ozbek S, Sert M, Paydas S et al. Delay in the diagnosis of SLE: the importance of arthritis/arthralgia as the initial symptom. Acta Med Okayama 2003; 57: 187–90.
14. Pratt AG, Lendrem D, Hargreaves B et al. Components of treatment delay in rheumatoid arthritis differ according to autoantibody status: validation of a single-centre observation using national audit data. Rheumatology (Oxford). 2016; 55: 1843–1848.
15. De Cock D, Meyfroidt S, Joly J et al. A detailed analysis of treatment delay from the onset of symptoms in early rheumatoid arthritis patients. Scand J Rheumatol 2014; 43: 1–8.
16. Potter T, Mulherin D, Pugh M. Early intervention with disease-modifying therapy for rheumatoid arthritis: where do the delays occur? Rheumatology (Oxford) 2002; 41: 953–955.
17. Nelson-Piercy C, Vlaev I, Harris K et al. What factors could influence physicians’ management of women of childbearing age with chronic inflammatory disease? A systematic review of behavioural determinants of clinical inertia. BMC Health Serv Res 2019; 19: 863.
18. Krause ML, Amin S, Makol A. Use of DMARDs and biologics during pregnancy and lactation in rheumatoid arthritis: what the rheumatologist needs to know. Ther Adv Musculoskelet Dis 2014; 6: 169–84.
19. Castro LL, Lanna CCD, Rocha MP et al. Recognition and control of hypertension, diabetes, and dyslipidemia in patients with rheumatoid arthritis. Rheumatol Int 2018; 38: 1437–1442.
20. Monk HL, Muller S, Mallen CD et al. Cardiovascular screening in rheumatoid arthritis: a cross-sectional primary care database study. BMC Fam Pract 2013; 14: 150.
21. Rollefstad S, Ikdahl E, Wibetoe G et al. An international audit of the management of dyslipidaemia and hypertension in patients with rheumatoid arthritis: results from 19 countries. Eur Heart J Cardiovasc Pharmacother 2021: pvab052. doi: 10.1093/ehjcvp/pvab052. Epub ahead of print. PMID: 34232315.
22. Semb AG, Rollefstad S, Ikdahl E et al. Diabetes mellitus and cardiovascular risk management in patients with rheumatoid arthritis: an international audit. RMD Open 2021; 7: e001724. doi: 10.1136/rmdopen-2021-001724. Erratum in: RMD Open 2021; 7: PMID: 34244381; PMCID: PMC8268901.