Towards Patient-Centered Care in Osteoarthritis: Patients’ Values as a Compass for Clinical Decision
Osteoarthritis (OA) is a chronic condition that occurs frequently in older age and typically requires multiple different treatments over the course of disease. Older patients often have comorbidities and are at an increased risk of cardiovascular, gastrointestinal, and renal adverse events which impact on the choice of OA medication. In a Mylan-sponsored symposium during the virtual WCO-IOF-ESCEO Congress, August 20–22, 2020, Dr Mickaël Hiligsmann discussed the importance of taking the patient’s preference into consideration when selecting an appropriate drug for OA. Dr Stefania Maggi assessed the wealth of studies that give clear indications for which drugs are safest as OA treatment and form the basis for clinical practice recommendations. Lastly, Professor Jean-Yves Reginster reviewed data on symptomatic slow-acting drugs for OA, identifying prescription crystalline glucosamine sulfate as the treatment of choice for superior efficacy, safety, and cost-effectiveness.
The Value of Patients’ Preference Research for Improving OA Care
Dr Mickaël Hiligsmann
Associate Professor in Health Economics and Health Technology Assessment
Department of Health Services Research, CAPHRI Care and Public Health Research Institute
Maastricht University, The Netherlands
The patient perspective is becoming increasingly important in health research, regulatory processes, treatment guidelines, and clinical decision-making.1-3 Indeed, information about what patients’ need and prefer, and how they value various aspects of a health intervention can be useful when designing and evaluating healthcare programs.4 Furthermore, insights into patients’ preferences and patient involvement in shared decision-making processes can lead to improved adherence to therapy and ultimately result in improved care.5
In line with this trend, there has been a growing interest in obtaining patients’ preferences for healthcare treatments that are deemed ‘preference sensitive’.6 To this end, the use of stated-preference studies, including discrete-choice experiments (DCE), conjoint analysis, and best-worst scaling has increased markedly. Preference-sensitive treatments are those in which there are trade-offs between health benefits and risks and the patient’s consideration of these factors is of utmost importance in the use of such treatments. The DCE study design is widely used and commonly perceived as the gold standard to elicit patients’ preferences.7 A main assumption of DCE is that a treatment can be broken down into its attributes, such as effectiveness, side effects and mode of administration, and that the utility a person receives from the treatment is a combination of these attributes.6
OA is the most common form of arthritis that frequently affects joints of the hand, knee and/or hip. It is characterized by pain and substantial reduction in a patient’s mobility and quality of life. Current treatment options aim to improve these factors. Given the significant challenges and lack of therapeutic options for OA, several stated-preference studies have been conducted to investigate OA treatment preferences. There is evidence from stated-preference studies in OA suggesting that potential benefits and risk of side effects are the most influential characteristics for both patients and physicians.8,9 In a study of people with self-reported chronic, moderate-to-severe OA pain, the most important attributes of potential analgesic treatments were identified by DCE as improvement of symptom control and reduced risk of physical dependence.9
Results of a recent DCE study from an ESCEO working group conducted in 253 patients with OA in seven European countries found that while patients viewed all treatment attributes as important, the most important for patients were impact on disease progression and improvement in pain and walking (Figure 1).10 Some variations in preferences were observed between patients and countries.10 For example, patients from Belgium, Portugal and France, women, patients with hip OA and patients receiving OA treatment were more likely to be concerned mainly by the impact on disease progression. Conversely, patients from Italy were more often focused on improvement in walking and overall energy.10
In summary, it is important to elicit and take the patient’s preference into consideration when selecting an appropriate drug for the patient. All patients should be made aware that there is a choice, be effectively informed of the expected outcomes and characteristics associated with each option and given the opportunity to discuss their views with the physician regardless of their desire to make or to avoid decision making. The use of stated-preference studies is feasible in OA and provides relevant information regarding preferences for OA treatment. Further insights into the preferences of patients will be useful to optimize policy and clinical decision-making through healthcare decision-making that better reflects patients’ preferences.
Figure 1. The most important treatment attributes identified by patients with osteoarthritis in a discrete-choice experiment10
Figure 1: Adapted from Hiligsmann M er al. Sem Arthritis Rheum 2020 50;859-66
A Critical Appraisal of Drug Safety in the Treatment of OA
Dr Stefania Maggi
Director, Aging Section, National Research Council (CNR)
Padova, ItalyPadua, Italy
OA is a chronic, progressive disorder that typically requires multiple treatment modalities over the course of disease. It occurs frequently in older age, and older patients often have comorbidities and are at an increased risk of cardiovascular (CV), gastrointestinal (GI) and renal adverse events (AEs) which impact on the appropriate choice of OA medication.11 The ESCEO algorithm for the management of knee OA sets out a step-wise, multi-modal approach to therapy allowing practitioners to optimize OA management in daily practice.12 Recommendations are based on the balance of relative benefits and harms of the treatment and patients’ values and preferences.12 Recognizing the need for a substantial evidence base upon which recommendations can be founded, the ESCEO convened a working party to provide new systematic reviews and meta-analyses on the safety of medications frequently prescribed to treat OA.
Paracetamol is widely recommended as the first-line analgesic for OA, but recent evidence suggests low efficacy for OA pain and potential safety issues, related to liver and GI toxicity, particularly in older patients.13 As background therapy, symptomatic slow-acting drugs for OA (SYSADOAs) include several different agents, such as glucosamine, chondroitin, diacerein, and avocado soybean unsaponifiables (ASU), for which safety and AEs vary.14 Thus, only prescription-SYSADOAs, not over-the counter products are recommended, and, in particular, prescription crystalline glucosamine sulfate (pCGS) and prescription chondroitin sulfate (CS) represent first-line treatment because of their efficacy in controlling pain and improving function in OA with no significant increased risk of AEs versus placebo, in a systematic review and random-effects meta-analyses of randomized, double-blind, placebo controlled trials (Figure 2).12 Safety issues related to the use of glucosamine sulfate in people with diabetes and CV disease have been addressed in clinical trials. These trials found that glucosamine sulfate at oral recommended doses for OA treatment showed no interference with glucose metabolism in normoglycemic subjects and in those with hyperglycemia, prediabetes, or diabetes.15 Conversely, several AEs have been reported for diacerein, including severe diarrhea and dizziness that in older, frail patients may be regarded as potentially serious AEs.14
Topical nonsteroidal anti-inflammatory drugs (NSAIDs), are recommended, particularly for older patients at higher risk for GI, CV and renal AEs, as add-on analgesia in patients still symptomatic after the use of pCGS or CS; only minor, local AEs have been associated with their use.16 Conversely, oral NSAIDs (non-selective NSAIDs and selective COX-1 and COX-2s) possess wide ranging toxicities affecting GI, CV, and renal systems. Consequently, a cautious approach to use of oral NSAIDs for OA is advisable, limiting their application to intermittent or cyclical use rather than chronic treatment to minimize safety concerns.17,18
Intra-articular hyaluronic acid (IAHA) is recommended as a treatment option in the case of a contraindication to NSAIDs (e.g. in older patients with comorbidities, and patients who did not respond to earlier treatment).12 IAHA has a good safety profile identified through systematic review and meta-analyses, although the certainty of evidence was only low to moderate grade and more evidence is needed.19 The use of opioid analgesia may be considered as a last resort pharmacologic therapy in OA when the pain is severe, when patients have not responded to other therapies, and when surgery is not considered appropriate. Oral opioids are associated with an increased risk of GI, dermatologic, and central nervous system-related AEs, and should be reserved for use only after other analgesic options are exhausted.20 In summary, clear indications for which drugs are safer as OA treatment are available and clinical practice should reflect the available recommendations.12
Figure 2: Honyo G et al. Drugs Aging 2019;36:545-564
What Makes a A Difference Between SYSADOAs?
Professor Jean-Yves Reginster
Director, WHO Collaborating Center for Public Health Aspects of Musculoskeletal Health and Aging, Liège, Belgium
Chair for Biomarkers of Chronic Diseases, Biochemistry Department, College of Science, King Saud University, Riyadh, KSA
In the 2019 ESCEO guidelines for the management of knee OA, SYSADOAs were upgraded and are now recommended as the first-line background therapy in symptomatic patients, due to the increase in concerns about the safety of paracetamol.12 However, there are many different agents in the class of SYSADOAs including glucosamine, chondroitin, diacerein, and avocado soybean unsaponifiables (ASU), which are supported by varying degrees of clinical efficacy data. Moreover, the availability of both over the counter (OTC) and prescription-grade SYSADOA products varies widely from country to country, which can make appropriate prescribing of SYSADOAs challenging. The ESCEO clearly states that whereas pCGS and prescription CS have shown their ability to improve pain and function, these results cannot be extrapolated to other SYSADOAs. Conversely, the ESCEO gives a weak recommendation for the use of SYSADOAs other than pCGS and prescription CS (i.e. ASU and diacerein) as an alternative background therapy as evidence for their efficacy and safety is scarcer than that for pCGS and prescription CS.12
The assessment of the respective SYSADOAs for the management of OA is based on three major pillars. Firstly, the efficacy of the drug should be unequivocally demonstrated in double-blind randomized placebo-controlled trials assessing pain and function through primary endpoints which have been validated by the regulatory authorities. Based on this, pCGS has shown its ability to reduce pain and improve function, mainly in patients with knee OA of grade 1–3.21,22 Moreover, there is now evidence that pCGS (1500 mg daily for the treatment of knee OA) combined with etoricoxib (60 mg daily) can repair articular cartilage through regulation of bone metabolism indices, delay joint degradation, and improve joint function.23
Secondly, since drugs for OA will be used for several years, their safety should be absolute, on all body systems and not only on the musculoskeletal tissues. In a systematic review and meta-analysis of randomized placebo-controlled trials (RCTs), CS was not associated with increased risk of AEs while for diacerein several AEs have been reported that may be cause for concern especially in older patients.14
Lastly, since we are living in a cost-conscious world, the cost-effectiveness of treatments against OA should be evaluated with a validated methodology, allowing comparison of the management cost of knee OA with different therapeutic approaches. pCGS has been shown to be cost-effective compared to placebo and compared to other preparations of glucosamine, in the short-term as well as after many years of administration.25,26 Using a new model to simulate individual health utility scores of patients included in ten published trials, incremental cost/effectiveness ratio (ICER) analysis showed that only the use of pCGS was cost-effective up to 3 years, (median ICER of €5,347.2/ quality-adjusted life year [QALY] at month 3, €4,807.2/QALY at month 6 and €11,535.5/QALY at year 3) while other formulations were not.27 The evolution of the health utility scores among studies that used pCGS or other forms of glucosamine was also examined (see Figure 3). This analysis found that the utility score always improved when pCGS was used, while the results are much more variable when other formulations of glucosamine were used.27 In conclusion, among SYSADOAs, pCGS may be the SYSADOA of choice for superior efficacy, safety, and cost-effectiveness.
Figure 3. Health utility evolution in trials having used pCGS or other forms of glucosamine27
Figure 3: Adapted from Bruyere O et al. Aging Clin Exp Res 2019;31:881-87
Treatment recommendations are based on the balance of relative benefits and harms of the treatment and patients’ values and preferences. Often the choice of medication is reduced to a trade-off between desirable and undesirable outcomes. Indications for which drugs are safer as OA treatments are now available and clinical practice should reflect the available recommendations. Among SYSADOAs for background OA therapy, pCGS may be the SYSADOA of choice for superior efficacy, safety, and cost-effectiveness. Further insights into the preferences of patients will be useful to optimize policy and clinical decision-making through healthcare decision-making that better reflects patients’ preferences. Ultimately, these research findings add to the evidence base on which future guideline updates may provide further clarity on the appropriate selection of OA medications tailored to the individual patient, so facilitating patient-centric care.
Report from a Mylan-sponsored symposium during the virtual WCO-IOF-ESCEO Congress, August 20–22, 2020