Osteoarthritis (OA) is a chronic musculoskeletal disorder characterized by the degeneration of cartilage and joints.1,2 Commonly reported risk factors for the development of OA include age, gender, and biomechanical factors such as joint loading due to obesity or misalignment.3,4 Pain is the most prominent and disabling symptom of OA patients. Pain is especially pronounced in patients with hip and knee OA as these are large weight-bearing joints.5–7 In Latin America, the knee is the most frequently impacted joint in OA patients (31.2%–51.1%). OA of the hip occurs less frequently and is estimated to impact 1.3% of OA patients.3,8

Globally, OA is estimated to impact 4.2% of the population.9 The burden of OA is projected to increase significantly in the future due to a combination of factors inclusive of an aging population, migration, and urbanization.9 In Mexico, OA represents the most common rheumatic disease with prevalence estimates as high as 32% depending on the clinical definition of OA and the population in which prevalence is assessed.6,8–11 Higher prevalence rates have been reported in specific geographies, older patient populations, and in women.6 For example, the prevalence and impact of musculoskeletal and rheumatic diseases are particularly pronounced among the indigenous people of Latin America, inclusive of Mexico, due primarily to the physically demanding lifestyles in this population. A cross-sectional, community-based census study reported an OA prevalence as high as 32.2% in selected indigenous subpopulations. 11

The Global Burden of Disease Study reports that musculoskeletal disorders, inclusive of OA, were ranked as one of the top ten contributors to disability in Mexico in 2016.9,12 In Latin America, patients with symptomatic OA have been found to experience prolonged pain episodes, functional limitations, and worse general health status.11,13–15 These studies highlight the high impact nature of OA and underscore the need for additional attention to patient treatment and management across several patient populations.

Clinical practice guidelines are primarily focused on the management of pain and recommend a range of pharmacologic therapies, such as paracetamol, nonsteroidal anti-inflammatory drugs (NSAIDs), and opioids, in addition to non-pharmacologic disease management approaches.16–18 Despite the availability of multiple treatment options, effective pain management is not achieved for many OA patients. There are a number of challenges with successful management of pain in individuals with OA, which include delayed diagnosis and treatment, limited treatment duration, unpredictable outcomes and effectiveness, patient-directed alterations in treatment regimens based on symptom severity, side effects, and increasing popularity in traditional medicines despite potential limitations.13,19 Additionally, clinical guidelines may be unclear and challenging for treating physicians to implement in daily practice and social inequalities may limit access to appropriate care.16,20,21

There is limited data that characterizes patients who experience moderate to severe pain despite analgesic treatment in Mexico. A cross-sectional, observational study completed in Latin America evaluated patients with symptomatic knee OA. This study reported that even among the 71% of patients that had taken medications, pain was persistent, suggesting the presence of an ongoing unmet need in this patient population.13 In Mexico, 28.5% of OA patients experienced pain improvement with medications and 7.1% with rest and medications.13 A multinational European study also quantified the burden of inadequate pain relief (IPR), estimating an IPR prevalence of 54% of knee OA patients and demonstrating significant associations between IPR and worse health-related quality of life (HRQoL) or increased functional limitation.22 The European survey of osteoarthritis real world therapies (SORT) study focused on western European countries (United Kingdom, France, Germany, Portugal, Italy, and the Netherlands), and thus are not generalizable to other regions of the world.22

In this study, which has been completed in the Philippines, Thailand, Russia, Mexico, and China, we aim to estimate the real-world prevalence of IPR among individuals with knee and/or hip OA who have been prescribed analgesic therapy, characterize this patient population for each country, and assess the impact of IPR on patient reported outcomes (PRO) inclusive of HRQoL, utilities, function, work productivity, and activity impairment. The results from the Mexico cohort are presented in this paper.

A geographically dispersed sample of 35 physicians actively treating patients with OA of the knee and/or hip were included in the study. During study recruitment, 377 total physicians were screened and contacted for participation and 62 responded to participate. The characteristics of the participating physicians (N=35) are provided in Table 1. The physicians were mostly male (65.7%) and between the ages of 30–49 (82.9%). Most physicians were either rheumatologists (42.9%) or orthopedist/orthopedic surgeons (31.4%), and 74% had teaching responsibilities.

The patient baseline characteristics are presented in Table 2. The mean age of all patients (N=301) included in the study was 65.2±9.6 years. There was a predominance of females in our study sample (73.4%). Most patients in the study had knee OA (70.8%), and 59% of patients had reports of OA in more than one joint.

All patients in the study received analgesic therapy for at least 30 days prior to study enrollment. On average patients received 2 different classes of pain medications. The most commonly prescribed treatment was NSAIDs (84.4%), followed by paracetamol (33.2%), chondroprotective compounds (16.6%), and opioids (15.6%).

About half of the patients were categorized as having IPR (N=158; 52.5%). Patients with IPR were significantly older than patients without IPR (66.8 vs. 62.5 years; p=0.002). The mean body mass index (BMI) was 28.6kg/m2 for all patients, however those with IPR had significantly higher BMI compared to patients without IPR (29.2kg/m2 vs. 28.0kg/m2; p=0.040) and a significantly higher proportion of IPR patients were categorized as obese (24% vs. 12%; p=0.006).

The predictors of IPR identified from a logistic regression model included physician primary specialty and academic responsibilities, and patient characteristics including age, BMI, depression, diabetes, and hyperlipidemia (all p<0.05). Specifically, patients older than 70 years of age had 2.5 times higher chance of having IPR than those younger than 60 years old (p=0.013). Obese patients were also 2.5 times more likely to have IPR compared to patients with normal BMI (p=0.036).

Patients with IPR reported more problems with each of the five dimensions of the EQ-5D. For example, moderate to severe problems with mobility was reported in 71.5% of patients with IPR and 37.1% of patients without IPR (p<0.001). Additionally, patients reporting the presence of IPR were more likely to report that they were either severely or extremely anxious or depressed (0.7% vs. 20.3%). Table 3 summarizes the patient-reported problems with each of the dimensions of the EQ-5D.

Overall, patients with IPR reported less treatment satisfaction compared to patients without IPR (25% vs. 67%, p<0.001). The adjusted means for PRO outcomes from multivariable analysis are summarized in Table 4. Overall, patients with IPR reported worse scores across all PROs. Results were statistically significant (p<0.05) for all comparisons except absenteeism, presenteeism, and work productivity, which were assessed using the WPAI. Compared to patients without IPR, patients with IPR reported lower EQ-5D VAS score (75.5 vs. 61.3, p<0.001) and EQ-5D Index (0.771 vs. 0.656, p<0.001). WOMAC scores were higher among patients with IPR in all three subdomains (all p<0.001). WPAI activity impairment score was higher in patients with IPR (52.1 vs. 29.3, p<0.001).

To our knowledge, this is the first study to evaluate the real-world occurrence and impact of IPR in OA patients in Mexico. This study demonstrates an association between IPR in OA patients receiving analgesics and HRQoL, function, work productivity, and daily activities. The results of the IPR-specific analyses were consistent with previous study reports on IPR in knee OA patients published for a European population.22

Our findings regarding the impact of pain, as the primary symptom of OA, are also consistent with studies assessing the overall impact and burden associated with OA.13–15 In a cross-sectional, community study of 439 OA patients, Esquivel-Valerio et al., assessed the impact of OA in a low-income urban population in Mexico.15 The authors showed that patients with OA had a poorer perception of their health compared to the general population and reported greater disability (Health Assessment Questionnaire – Disability Index [HAQ-DI]), more functional limitations, and greater pain and discomfort.15 Similarly, a hospital based cross-sectional study completed in Mexico examined disease activity scores (DAS28), the HAQ-DI, and WOMAC among other measures to quantify the impact of OA in comparison with other chronic diseases. In this study, Ambriz Murillo et al., concluded that patients with OA and other rheumatic diseases experienced more pain than patients with other chronic conditions (i.e., end-stage renal disease, diabetes).14

Possible explanations for persistent IPR may include lack of non-pharmacologic interventions (e.g., weight control), poor treatment effectiveness, decline in effectiveness over time, poor patient management, presence of comorbidities, or barriers to treatment access/health care system characteristics. An analysis of data collected for an indigenous patient population in Latin America suggests that access to medical care is a particular challenge – 40.6% of this patient population reported having never sought medical or traditional treatment despite reports of pain, disability, and challenges with coping.11 Further research is needed to understand system factors that may be contributing to the high prevalence of IPR and to help inform strategies for improved patient treatment and management.

As part of this study, we investigated the utilization of different pain medications in Mexico. Our finding that OA patients receive combination therapies or medications across multiple classes was consistent with larger population-based studies.3 Additionally the study results were in agreement with previously published literature that the most commonly used pain medications in Mexico are NSAIDs.3 An observational study of 3040 OA patients in Latin America reported that NSAIDs were used in 68.5% of the OA population in the region and 50.1% in Mexico. The same study reported higher utilization of vicosupplementation (27.5%) in Mexico compared to other countries compared to other countries in the region, which was an observation that was not replicated in our current study.3 Additional studies from Mexico have reported NSAID utilization rates between 50 and 60%.8,13,20

There are limitations to the study which need to be acknowledged. First, the information in the chart could be incomplete, with patients receiving care from other physicians. Not all clinical outcomes that could influence physician-prescribing behavior or treatment decisions are necessarily measured and/or recorded in the chart. For example, patient compliance to prescribed treatment regimens was not assessed as part of this study. Moreover, there exists potential recall bias in PROs as they were provided by the patients. Second, there is a potential selection bias in patient selection, and the prevalence derived from the study is estimated from a convenient sample. Therefore, the estimates are not population-derived. Third, because of the cross-sectional nature of conducting the survey, causal relationship between IPR and PROs may not be established. The results should be interpreted with these limitations in mind.

A large proportion of patients with OA in Mexico suffer from IPR (52.5% of the study population), which is associated with significant impairment in patient's quality of life and functional status.

This study was sponsored by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

Kelly Johnson, Dena Ramey, Fidel Lozano, Ishita Doshi, and Kaan Tunceli are employees of Merck Sharp & Dohme Corp. Jyoti Aggarwal is an employee of Pharmerit International and was a paid consultant to Merck Sharp & Dohme Corp. in connection with this study. Cynthia Macahilig is an employee of Medical Data Analytics, and was a paid consultant to Merck Sharp & Dohme Corp. in connection with this study. Ruben Burgos-Vargas was a paid consultant to Merck Sharp & Dohme Corp. in connection with this study.