Evidence for key individual characteristics associated with outcomes following combined first-line interventions for knee osteoarthritis: A systematic review

Abstract

Objective: To identify individual characteristics associated with outcomes following combined first-line interventions for knee osteoarthritis.

Methods: MEDLINE, CINAHL, Scopus, Web of Science Core Collection and the Cochrane library were searched. Studies were included if they reported an association between baseline factors and change in pain or function following combined exercise therapy, osteoarthritis education, or weight management interventions for knee osteoarthritis. Risk of bias was assessed using Quality in Prognostic Factor Studies. Data was visualised and a narrative synthesis was conducted for key factors (age, sex, BMI, comorbidity, depression, and imaging severity).

Results: 32 studies were included. Being female compared to male was associated with 2-3 times the odds of a positive response. Older age was associated with reduced odds of a positive response. The effect size (less than 10% reduction) is unlikely to be clinically relevant. It was difficult to conclude whether BMI, comorbidity, depression and imaging severity were associated with pain and function outcomes following a combined first-line intervention for knee osteoarthritis. Low to very low certainty evidence was found for sex, BMI, depression, comorbidity and imaging severity and moderate certainty evidence for age. Varying study methods contributed to some difficulty in drawing clear conclusions.

Conclusions: This systematic review found no clear evidence to suggest factors such as age, sex, BMI, OA severity and presence of depression or comorbidities are associated with the response to first-line interventions for knee OA. Current evidence indicates that some groups of people may respond equally to first-line interventions, such as those with or without comorbidities. First-line interventions consisting of exercise therapy, education, and weight loss for people with knee OA should be recommended irrespective of sex, age, obesity, comorbidity, depression and imaging findings.

Fig 1. PRISMA 2020 flow diagram of selected studies.

Fig 2. Summary of risk of bias assessment using Quality in Prognostic Studies (QUIPS) according to the six domains of the 32 included studies.

Fig 3. Effect of increasing age and female sex on the odds of positive response following a combined first-line intervention for knee osteoarthritis.

All graphs report the log odds ratio and 95% CI. Repeated study labels by the same author represent multiple responder definitions within each study. The OR for sex reports the probability of a female (compared to a male) being a responder. OR > 1 = increased probability of female being a responder compared to a male. OR > 1 for age interpreted as increased probability of being a responder with increasing age. For age, original data from 8 studies reporting OR (7 cohorts, one secondary analysis of RCT). Studies not included: 2 reporting regression coefficients [25, 42] and 3 MD [15, 16, 37] and 1 HR [36]. For sex, original data from 8 cohort studies reporting OR. Studies not included: 3 reporting MD [15, 16, 37] and 1 HR [36]. 1. Ernstgard 2017 is grouped by ages and represents the OR of 75–100 years, 65–74 years, 55–64 years compared to 22–54 years [29].

Fig 4. Effect of depression and increased BMI on the odds of positive response following a combined first-line intervention for knee osteoarthritis.

Graph reports the log odds ratio and 95% CI. Repeated study labels by the same author represent multiple responder definitions within each study. Graph plots the odds ratio for the probability of BMI or presence of depression on a positive response following intervention. For BMI, OR >1 = increased probability of being a responder with increased BMI. For depression, OR > 1 = increased probability of being a responder with the presence of depression. For a continuous predictor, we interpret the odds ratio per one unit change, and for a dichotomised predictor, the OR is the probability compared to the reference group. For depression, original data from 7 studies (5 cohorts) reporting OR. Studies not included: 1 reporting a regression coefficient [42] and 2 mean difference [37, 41]. For BMI, original data from 5 cohort studies reporting OR. Studies not included: 1 reporting regression coefficient [25], 2 MD [16, 37] and 1 unadjusted HR [36]. HADS = Hospital Anxiety Depression scale, PHQ-8 = Patient Health Questionnaire, BECKII = Beck Depression Inventory, DASS21 = Depression and Anxiety Stress scale, CES-D = Centre for Epidemiologic Studies Depression scale.

Fig 5. Presence of comorbidity on the odds of a positive outcome following a combined first- intervention for knee osteoarthritis.

Graph reports the log odds ratio and 95% CI. Repeated study labels by the same author represent multiple responder definitions within each study. OR > 1 for comorbidity interpreted as increased probability of being a responder with the presence of comorbidity. For a continuous predictor, we interpret the log-odds change with a one-unit change in comorbidity score. For dichotomised predictor, the OR is the probability of the comorbidity category to the reference group of being a responder. Original data from 7 studies reporting OR. Studies not included:2 reporting regression coefficient [25, 47], 2 mean differences [37, 41] and 1 unadjusted hazard ratio [36]. SCG = self-administered comorbidity questionnaire. Charnley classification = Charnley A (unilateral hip or knee OA), B (bilateral hip or knee OA), C (multiple joint sites hip and knee and presence of other disease affecting walking ability). Self-report = presence of one comorbidity or number of self-reported comorbidities.1. Lee2018b used multinomial logistical regression with multiple outcome definitions based on four group-based trajectories of WOMAC pain and function. OR > 1 indicates an increased probability of being in the lower pain, early improvement group. 2. There are six OR reported for Eyles (2016) due to multiple responder definitions and the number of comorbidities reported as low, moderate, and high.