The Burden of Pain Associated with Osteoarthritis in the Hip or Knee from the Patient’s Perspective: A Multinational Cross-Sectional Study

This study utilized data from the Adelphi Disease Specific Programme (DSP)™, which is a large, multinational, observational study designed to capture a cross-section of real-world data for a range of common chronic diseases [20]. This study used de-identified, aggregated patient data and was granted exceptions from requiring ethics approval. Patients provided consent to participate. Data were collected in clinical practice settings by physicians who provided relevant information on consecutive patients consulting for the disease of interest. Patients were invited to participate by completing an independent questionnaire. Data were drawn from the 2017 global Adelphi OA DSP, which surveyed primary care physicians, rheumatologists, orthopedists, and their patients with OA during their regular office visits. Physician and patient data were collected at the same time. Participating physicians and patients were each assigned a study number to aid anonymous data collection and to allow linkage of data during data collection and analysis. This study included patients from the US and the five most populated EU countries at the time of the analysis (Germany, France, UK, Italy, and Spain [21]) who were diagnosed with OA of the knee and/or hip by their consulting physicians. For each included patient, during the visits physicians completed a patient record form on the patient’s history of OA treatment regimens, current use of opioids and other treatments for OA pain, and comorbidities. Patients who agreed to participate completed a self-assessment form that included questions and validated measures for evaluating disease burden. OA pain intensity in the past 48 h was measured using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Numerical Rating Scale (NRS) 3.1, a widely used, validated, self-administered, disease-specific questionnaire [22,23]. Using the pain component of the WOMAC, patients were stratified by no/mild pain (score 0–3) and moderate/severe pain (score 4–10) and at the same time by the presence or absence of current opioid use, resulting in four groups: no/mild pain without current opioid use; no/mild pain with current opioid use; moderate/severe pain without current opioid use; moderate/severe pain with current opioid use.

Outcomes included measures for physical functioning, unmet treatment needs, comorbidity, HRQoL, and work productivity and daily activity. Physical functioning was reported by patients using physical function and stiffness scores from the WOMAC NRS 3.1, which are scored on a range from 0 to 10, with higher scores indicating a worse condition over the past 48 h [22,23]. Physical functioning was also assessed by patient responses to stand-alone questions related to functional limitations (“Has your mobility been impacted due to your OA?” “Do you need an aid to get around, either inside or outside of your house due to your OA?” “Do you need anyone to help you with any daily activities or tasks?” “Have you ever suffered a fall inside or outside of your home that you believe was because of your OA?”); these questions were not previously validated. Unmet treatment needs were measured by the use of ≥ 3 treatment regimens for OA and patient-reported dissatisfaction with treatment. Comorbidity burden was evaluated by the physician using the Charlson Comorbidity Index (CCI) [24]. To further examine relevant comorbidities, rates of any cardiovascular condition, hypertension, depression or anxiety, osteoporosis, and chronic low back pain were recorded by the physician.

HRQoL was measured using the 5-dimension, 5-level EuroQol (EQ-5D-5L), a generic, patient-reported measure of health status [25]. The EQ-5D-5L consists of five dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression), with five levels of impairment responses, and a health state visual analog scale (VAS; 0 = worst health state, 100 = best health state). Patient responses on the five dimensions are used to generate a utility index that represents a health state with anchors at 0 (death) and 1 (perfect health), although index scores < 0 are possible. For the EQ-5D-5L utility index, individual country value sets were used for the US and EU countries. The minimally important difference (MID) for the EQ-5D-5L utility index is estimated to be a difference of > 0.037 to 0.069 points [26].

Work productivity and daily activity over the past 7 days were assessed using the patient-reported Work Productivity and Activity Impairment Questionnaire: Specific Health Problem (WPAI:SHP) version 2.0, with OA as the specified disease [27]. Activity impairment was assessed among all patients; work productivity was assessed among employed patients only. Assessed WPAI:SHP scales were impairment while working due to problem (“presenteeism”), work time missed (“absenteeism”), overall work impairment, and activity impairment.

The study sample comprised 2170 patients with OA of the knee and/or hip from the 2017 global Adelphi OA DSP (Table 1). The mean age was 66.4 years, 57.9% of patients were female, and 88.4% were white or Caucasian. OA was reported in the knee (without hip), hip (without knee), or both hip and knee in 54.9%, 24.6%, and 20.5% of patients, respectively (OA may have been present in joints other than the knee or hip). Participating patients were from the US (n = 623; 28.7%) and EU (n = 1547; 71.3%).

Among the study sample, 1090 patients (50.2%) had moderate/severe pain and 648 patients (29.9%) were currently receiving opioids. Despite current opioid treatment, 427 of the 648 patients (65.9%) still reported moderate/severe pain. Based on pain severity and opioid use, patients were grouped into four categories: 859 patients (39.6%) had no/mild pain without opioid use, 221 patients (10.2%) had no/mild pain with opioid use, 663 patients (30.6%) had moderate/severe pain without opioid use, and 427 patients (19.7%) had moderate/severe pain with opioid use (Supplementary Fig. 1).

Demographic and clinical characteristics were generally consistent across the four categories, although patients with moderate/severe pain with opioid use were older, had a higher proportion of females, had a higher incidence of OA affecting both the knee and hip, and had a higher incidence of obesity (Table 1). Moderate/severe pain was reported by 248 of 623 US patients (39.8%) and 842 of 1547 EU patients (54.4%), and opioids were used by 141 US patients (22.6%) and 507 EU patients (32.8%; Supplementary Fig. 1). Opioids were used by 46.1% of patients in Spain, 39.8% of patients in the UK, 29.7% of patients in Italy, 27.4% of patients in Germany, and 25.5% of patients in France (Supplementary Fig. 2). Despite receiving opioids, 93 patients (14.9%) in the US cohort and 334 patients (21.6%) in the EU cohort still reported moderate/severe pain (Supplementary Fig. 1). The proportion of patients with moderate/severe pain and opioid use was 33.3% in Spain, 25.7% in the UK, 23.9% in Italy, 16.7% in France, and 15.0% in Germany (Supplementary Fig. 2).

In the total population, patients with moderate/severe pain reported higher scores in WOMAC physical function and stiffness than patients with no/mild pain, which was indicative of higher functional impairment (Fig. 1). In addition, patients with opioid use reported more physical function limitations than those without opioid use at the same pain level (i.e., patients with no/mild pain with opioid use had more limitations than those with no/mild pain without opioid use, as did patients with moderate/severe pain with opioid use versus those without opioid use; Fig. 1a). Patients with moderate/severe pain with opioid use experienced the most limitations in physical function and joint stiffness. WOMAC physical function and stiffness scores were more than twofold higher among patients with moderate/severe pain with or without opioid use compared with those with no/mild pain without opioid use (6.3 and 5.7 versus 2.5 [p < 0.05] and 6.3 and 5.7 versus 2.7 [p < 0.05], respectively). Patterns were similar in the US and EU cohorts (Fig. 1).

Higher rates of mobility limitation, need for a walking aid, need for help with daily activities, and suffering a fall were noted with moderate/severe pain than with no/mild pain (Table 2). Similarly, the prevalence of these limitations was higher among those with opioid use relative to those without opioid use at the same pain level (Table 2). These burdens were highest in patients with moderate/severe pain with opioid use and when compared with those with no/mild pain without opioid use showed more than a twofold higher need of a walking aid (67.3% versus 30.0%; p < 0.05), almost a fivefold higher need for help with daily activities (48.9% versus 10.2%; p < 0.05), and more than a twofold higher fall rate (45.3% versus 17.6%; p < 0.05). Patterns for functional burdens were similar in the US and EU cohorts (Supplementary Tables 1 and 2).

Treatment needs (i.e., the requirement for three or more treatment regimens for OA pain or dissatisfaction with treatment) were higher with moderate/severe pain than with no/mild pain and with opioid use than with no opioid use at the same pain level (Table 2). Patients with moderate/severe pain with opioid use reported the greatest treatment needs. Among patients with moderate/severe pain with opioid use in the total population, approximately half (50.1%) reported using three or more treatment regimens for OA pain and more than one-third (38.1%) reported being dissatisfied with their treatment. Patterns in treatment needs were similar across the US and EU cohorts (Supplementary Tables 1 and 2).

In the total population, the mean CCI score was approximately twofold higher among patients with current opioid use than those without opioid use at the same severity level (Fig. 2). Patients with moderate/severe pain with opioid use had the highest mean CCI score, which was significantly higher than those with no/mild pain without opioid use (0.74 versus 0.30, respectively; p < 0.05; Fig. 2). These trends were also observed in the US and EU cohorts.

Relevant comorbid conditions were more prevalent among patients with moderate/severe pain than among those with no/mild pain, as well as among patients with opioid use than among those with no opioid use at the same pain level (Table 2). Patients with moderate/severe pain with opioid use had the highest rates of comorbid conditions. Rates of depression or anxiety, osteoporosis, and chronic low back pain were more than twofold higher among patients with moderate/severe pain with opioid use compared with those with no/mild pain without opioid use (p < 0.05). The majority of patients with moderate/severe pain with opioid use had been diagnosed with any cardiovascular condition (72.1%) or hypertension (66.3%); more than one-third of these patients (34.4%) suffered from anxiety or depression. Rates of comorbidities were slightly higher in the US than in the EU cohort, although trends were similar between the two cohorts (Supplementary Tables 1 and 2).

HRQoL, as assessed by the EQ-5D-5L VAS and index scores, was lower among patients with moderate/severe pain than among those with no/mild pain as well as among those with opioid use than among those with no opioid use at the same pain level (Fig. 3). Differences in EQ-5D-5L index scores between patients with no/mild pain without opioid use and patients in the other three study groups were clinically relevant (i.e., exceeding the estimated MID of 0.037 [25]). Patients with moderate/severe pain with opioid use reported the poorest HRQoL. Mean EQ-5D-5L VAS and index scores were significantly lower among patients with moderate/severe pain with or without opioid use than among those with no/mild pain without opioids (p < 0.05). EQ-5D-5L VAS and utility index scores were slightly lower in the EU cohort than in the US cohort, although overall trends were similar.

In the total population, patients with moderate/severe pain reported greater percentages of work time missed due to problem (absenteeism; Fig. 4a), impairment while working due to problem (presenteeism; Fig. 4b), overall work impairment (Fig. 4c), and activity impairment (Fig. 4d) than patients with no/mild pain, as assessed by the WPAI:SHP. In addition, patients with opioid use generally reported greater percentage impairment on all WPAI:SHP scales than those without opioid use, regardless of pain level. The percentage of impairment due to presenteeism (Fig. 4b) exceeded that of absenteeism (Fig. 4a), regardless of pain level or opioid use.

In the total population, the greatest percentage impairment in WPAI:SHP scales was reported by patients with moderate/severe pain with opioid use. Patients with moderate/severe pain with or without opioid use, compared with those with no/mild pain without opioid use, reported significantly greater work productivity and daily activity impairment (p < 0.05; Fig. 4). Across WPAI:SHP scales, reported impairment was more than twofold higher in patients with moderate/severe pain with opioid use compared with those with no/mild pain without opioid use. WPAI:SHP results were generally consistent across US and EU cohorts. However, among patients with moderate/severe pain with opioid use, the percentage of overall work impairment was substantially greater in the EU cohort than in the US cohort (60.9% versus 41.8%; Fig. 4c), and absenteeism was more evident in the EU cohort than in the US cohort (Fig. 4a).