Andrea Thomson

Evaluation of Client‐Specific Outcome Measures and Activity Monitoring to Measure Pain Relief in Cats with Osteoarthritis

BACKGROUND There are no validated systems for measuring pain from osteoarthritis in cats. HYPOTHESIS Owner subjective assessments and an activity monitor (AM) can be used to detect pain in cats with osteoarthritis and to assess efficacy of treatments. ANIMALS Thirteen cats older than 10 years old, with owner-assessed decreases in activity, painful arthritic joints, and clinically normal blood work were included and evaluated for 3 weeks. METHODS A collar-mounted AM measured activity and a client-specific outcome measure (CSOM) questionnaire characterized the severity of impairment. Overall global quality of life was also evaluated for each treatment. In weeks 2 and 3, meloxicam (0.1 mg/kg, day 1; 0.05 mg/kg, days 2-5) or a placebo was administered in a blinded, randomized, cross-over manner to test the assessment systems. RESULTS The cats had a median of 4 arthritic appendicular joints. Activity counts for the week when cats (complete data on activity; n=9) were administered meloxicam were significantly higher than at baseline (P = .02) but not after placebo (P = .06). Baseline activity counts were not significantly different from placebo (P = .6). The CSOM data (n=13) showed that owners considered their cats to be more active on meloxicam compared with baseline (P = .001) and placebo (P < .004), and more active on placebo than at baseline (P < .01). Global quality of life improved significantly with meloxicam (P < .042). CONCLUSIONS AND CLINICAL IMPORTANCE Both an AM and a CSOM system can detect behavior associated with pain relief in cats that are arthritic. Objective activity data might allow subjective assessment systems to be validated for use in clinical studies.

Evaluation of a Therapeutic Diet for Feline Degenerative Joint Disease

BACKGROUND Feline degenerative joint disease (DJD) is common and there are no approved therapies for the alleviation of the associated pain. OBJECTIVE To test a diet high in eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) content and supplemented with green-lipped mussel extract and glucosamine/chondroitin sulfate (test-diet) for its pain-relieving and activity-enhancing effects in cats with painful, mobility-impairing DJD over a 9-week period. ANIMALS Forty client-owned cats. METHODS Randomized, controlled, blinded, parallel group, prospective clinical study. Cats with no detectable systemic disease, and with at least 1 appendicular joint with radiographic evidence of DJD where manipulation elicited an aversive response were included. Cats were randomly allocated to the test-diet or control diet (C-diet). Outcome measures were subjective owner and veterinarian assessments, and objective activity monitoring (accelerometry). Nonparametric statistics were used to evaluate changes within and between groups for both subjective and objective data, and locally weighted scatterplot smoothing regression analysis was used to predict activity changes. RESULTS The primary objective outcome measures indicated that activity declined significantly (P < .001) in the C-diet group, significantly increased (P < .001) in the test-diet group and there was a significant difference between the groups (P < .001). CONCLUSION AND CLINICAL IMPORTANCE A diet high in EPA and DHA and supplemented with green-lipped mussel extract and glucosamine/chondroitin sulfate improved objective measures of mobility. Dietary modulation might be 1 method to use to improve mobility in cats with DJD-associated pain.

Relationship of orthopedic examination, goniometric measurements, and radiographic signs of degenerative joint disease in cats

BackgroundAvailable information suggests a mismatch between radiographic and orthopedic examination findings in cats with DJD. However, the extent of the discrepancy between clinical and radiographic signs of OA in companion animals has not been described in detail. This study aimed to evaluate the relationship between orthopedic examination findings, joint goniometry, and radiographic signs of DJD in 100 cats, in a prospective observational design. Cat temperament, pain response to palpation, joint crepitus, effusion and thickening were graded. Radiographs of appendicular joints and the axial skeleton were made under sedation. Joint motion was measured by use of a plastic goniometer before and after sedation. Associations between radiographic degenerative joint disease (DJD) and examination findings were assessed to determine sensitivity, specificity and likelihood estimations.ResultsPain response to palpation was elicited in 0-67% of the joints with DJD, with a specificity ranging from 62-99%; crepitus was detected in 0-56% of the joints and its specificity varied between 87 and 99%; for effusion, values ranged between 6 and 38% (specificity, 82-100%), and thickening, 0-59% (specificity, 74-99%). Joints with DJD tended to have a decreased range of motion. The presence of pain increased the odds of having DJD in the elbow (right: 5.5; left: 4.5); the presence of pain in the lower back increased the odds of spinal DJD being present (2.97 for lumbar; 4.67 for lumbo-sacral).ConclusionsRadiographic DJD cannot be diagnosed with certainty using palpation or goniometry. However, negative findings tend to predict radiographically normal joints. Palpation and goniometry may be used as a tool to help to screen cats, mostly to rule out DJD.

Reliability and discriminatory testing of a client-based metrology instrument, feline musculoskeletal pain index (FMPI) for the evaluation of degenerative joint disease-associated pain in cats

The objective of this study was to test the readability, reliability, repeatability and discriminatory ability of an owner-completed instrument to assess feline degenerative joint disease (DJD)-associated pain (feline musculoskeletal pain index, FMPI). Readability was explored using four different formulas (Flesch, Fry, SMOG and FOG) and the final FMPI instrument was produced. To assess the instrument, client-owned cats that were defined as normal (normal group) or as having DJD-associated pain and mobility impairment (pain-DJD group) were recruited. A total of 32 client-owned cats were enrolled in the study (normal, n=13; pain-DJD, n=19). Owners completed the FMPI on two occasions, 14days apart. Internal consistency (reliability) and repeatability (test-retest) were explored using Cronbachs α and weighted κ statistic, respectively. Data from the two groups were compared using analysis of covariance (controlling for age) to evaluate discriminatory ability. The FMPI was constructed with 21 questions covering activity, pain intensity and overall quality of life. It had a 6th grade readability score. Reliability of the FMPI was excellent (Cronbachs α>0.8 for all groupings of questions in normal and pain-DJD cats) and repeatability was good (weighted κ statistic >0.74) for normal and pain-DJD cats. All components of the FMPI were able to distinguish between normal cats and cats with DJD (P<0.001 for all components). This initial evaluation of the FMPI suggests that this instrument is worthy of continued investigation.

Dose reduction of meloxicam in dogs with osteoarthritis-associated pain and impaired mobility.

BACKGROUND Progressive nonsteroidal anti-inflammatory drug (NSAID) dose reduction appears logical; however, there is no evidence-based medicine indicating that efficacy is maintained as dose is reduced. OBJECTIVE To determine if NSAID dose can be reduced and pain relief and mobility can be maintained in dogs with osteoarthritis (OA). ANIMALS Client-owned dogs (n = 59) with OA-associated impaired mobility and pain. METHODS Prospective, randomized, blinded study. After 14 days wash-out, dogs were randomized to reducing dose (RDG) (n = 30) or maintenance dose (MDG) (n = 29). MDG received standard dose meloxicam. RDG received a reducing dose from D28 onward, reducing to 0% of maintenance for the final 2 weeks. Assessments were at D14, 28, 42, 56, 70, 84, 98 and 112 using subjective owner assessments, accelerometry (AM), and standing percent body weight distribution (%BW). A Kaplan-Meier survival curve described how dogs dropped out because of insufficient pain control. A Log-rank test compared the groups. RESULTS More dogs in RDG (13) dropped out because of owner-evaluated insufficient pain control compared with MDG (5) (P = .029; odds ratio: 3.67; median dropout time: 84 days in each group). For the dogs that did not drop out (n = 41), there were no significant differences between groups in owner assessments (P > .2 for each), %BW placed on the index limb (P = .750), or accelerometer-measured activity (P = .14). CONCLUSION AND CLINICAL RELEVANCE Dose reduction is a less effective means of pain control compared with maintained dosing. However, NSAID dose reduction with maintained efficacy is possible, but success appears to be individual dog dependent.

Feline Musculoskeletal Pain Index: Responsiveness and Testing of Criterion Validity

BACKGROUND Progress in establishing if therapies provide relief to cats with degenerative joint disease (DJD)-associated pain is hampered by a lack of validated owner-administered assessment methods. HYPOTHESIS That an appropriately developed subjective owner-completed instrument (Feline Musculoskeletal Pain Index-FMPI) to assess DJD-associated impairment would have responsiveness and criterion validity. ANIMALS Twenty-five client-owned cats with DJD-associated pain. METHODS FMPI responsiveness (ability to detect the effect of an analgesic treatment) and validity (correlation with an objective measure) were explored through a stratified, randomized, double blinded, placebo-controlled, crossover 10-week clinical study. Meloxicam was administered to effect pain relief. A linear mixed model, backward stepwise regression, and Pearson correlations were used to assess responsiveness and criterion validity with the assumption that the NSAID would increase activity. RESULTS Positive responses of cats to placebo (P = .0001) and meloxicam treatment (P = .0004) were detected; however, the instrument did not detect any difference between placebo and meloxicam (linear mixed model), even for the high impairment cases. Percent meloxicam target dose administered, temperament, and total baseline FMPI score were covariates that most affected FMPI scores. Controlling for significant covariates, most positive effects were seen for placebo treatment. Positive treatment effects on activity were detected, but only for the cases designated as most highly impaired. CONCLUSIONS AND CLINICAL IMPORTANCE Neither responsiveness nor criterion validity were detected by the inclusion criteria for cases in this study. The data suggest that further work is indicated to understand factors affecting activity in cats to optimize inclusion criteria.

Owner-assessed indices of quality of life in cats and the relationship to the presence of degenerative joint disease

This study evaluated the types of items owners consider important to their cats’ quality of life (QoL). We hypothesized that items contributing to QoL in cats are predominantly items requiring mobility. The objectives of the study were to describe the types of items considered important by owners for their cats’ QoL; to describe the proportion of these items that involve mobility; to evaluate what patient factors, including severity of degenerative joint disease (DJD), affect this distribution; and to evaluate whether the proportion of QoL items involving mobility chosen by owners is different in cats presenting for a DJD study compared with a randomly selected population. A total of 830 client-generated items were evaluated. Regardless of DJD status, 40% of items listed by owners involved mobility, while 60% were ‘inactive’ items, rejecting our hypothesis. This highlights the need to assess non-active items that owners consider to constitute QoL to fully assess the impact of diseases like DJD and, therefore, the success of therapeutic interventions.

Detection of Clinically Relevant Pain Relief in Cats with Degenerative Joint Disease Associated Pain

Background Detection of clinically relevant pain relief in cats with degenerative joint disease (DJD) is complicated by a lack of validated outcome measures and a placebo effect. Hypothesis/Objectives To evaluate a novel approach for detection of pain relief in cats with DJD. Animals Fifty‐eight client‐owned cats. Methods Prospective, double‐masked, placebo‐controlled, stratified, randomized, clinical study. Enrolled cats were 6–21 years of age, with owner‐observed mobility impairment, evidence of pain in at least 2 joints during orthopedic examination, and overlapping radiographic evidence of DJD, and underwent a 2‐week baseline period, 3‐week treatment period with placebo or meloxicam, and 3‐week masked washout period. Outcome measures were evaluated at days 0, 15, 36, and 57. Results Both groups significantly improved after the treatment period (day 36) on client‐specific outcome measures (CSOM) and feline musculoskeletal pain index (FMPI) (P < .0001 for both); there was no difference between the groups on CSOM or FMPI score improvement. After the masked washout period, more cats that received meloxicam during the treatment period had a clinically relevant decrease in CSOM score (P = .048) and FMPI score (P = .021) than cats that received placebo. Conclusions and Clinical Importance Using both a client‐specific and a general clinical metrology instrument, owners of cats with DJD were able to detect evident recurrence of clinical signs after withdrawal of active medication than after withdrawal of placebo, and that this study design might be a novel and useful way to circumvent the placebo effect and detect the efficacy of pain‐relieving medications.

Criterion Validation Testing of Clinical Metrology Instruments for Measuring Degenerative Joint Disease Associated Mobility Impairment in Cats.

Introduction Degenerative joint disease and associated pain are common in cats, particularly in older cats. There is a need for treatment options, however evaluation of putative therapies is limited by a lack of suitable, validated outcome measures that can be used in the target population of client owned cats. The objectives of this study were to evaluate low-dose daily meloxicam for the treatment of pain associated with degenerative joint disease in cats, and further validate two clinical metrology instruments, the Feline Musculoskeletal Pain Index (FMPI) and the Client Specific Outcome Measures (CSOM). Methods Sixty-six client owned cats with degenerative joint disease and owner-reported impairments in mobility were screened and enrolled into a double-masked, placebo-controlled, randomized clinical trial. Following a run-in baseline period, cats were given either placebo or meloxicam for 21 days, then in a masked washout, cats were all given placebo for 21 days. Subsequently, cats were given the opposite treatment, placebo or meloxicam, for 21 days. Cats wore activity monitors throughout the study, owners completed clinical metrology instruments following each period. Results Activity counts were increased in cats during treatment with daily meloxicam (p<0.0001) compared to baseline. The FMPI results and activity count data offer concurrent validation for the FMPI, though the relationship between baseline activity counts and FMPI scores at baseline was poor (R2=0.034). The CSOM did not show responsiveness for improvement in this study, and the relationship between baseline activity counts and CSOM scores at baseline was similarly poor (R2=0.042). Conclusions Refinements to the FMPI, including abbreviation of the instrument and scoring as percent of possible score are recommended. This study offered further validation of the FMPI as a clinical metrology instrument for use in detecting therapeutic efficacy in cats with degenerative joint disease.

A Feline-Specific Anti-Nerve Growth Factor Antibody Improves Mobility in Cats with Degenerative Joint Disease-Associated Pain: A Pilot Proof of Concept Study.

Background Neutralizing antibodies against nerve growth factor (NGF) are analgesic in rodent models, naturally occurring degenerative joint disease (DJD) pain in dogs, and chronic pain in humans. Objectives To evaluate the efficacy of a fully felinized anti‐NGF antibody (NV‐02) for the treatment of DJD pain and mobility impairment in cats. Animals Thirty‐four client‐owned cats with DJD‐associated pain and mobility impairment. Methods In a placebo‐controlled, pilot, masked clinical study, cats were randomized to a single treatment with NV‐02 (0.4 mg/kg SC [n = 11] or 0.8 mg/kg SC [n = 12]) or placebo (saline, SC [n = 11]). Activity was measured objectively. Additionally, owners completed clinical metrology instruments (client‐specific outcome measures [CSOM] and feline musculoskeletal pain index [FMPI]) on days 0 (screening), 14 (baseline), 35, 56, and 77. A repeated‐measures model was used to evaluate the objective activity data. Results NV‐02 significantly increased objectively measured activity overall (P = .017) and at 2 (P = .035), 3 (P = .007), 4 (P = .006), 5 (P = .007), and 6 (P = .017) weeks after treatment. CSOM scores (P = .035) and pain (P = .024) showed a significant effect of treatment 3 weeks after administration. In the treatment group, 83% of the owners correctly identified the treatment administered compared with 45% of owners in the placebo group (P = .013). No treatment‐related adverse effects were identified. Conclusions These pilot data demonstrate a 6‐week duration positive analgesic effect of this fully felinized anti‐NGF antibody in cats suffering from DJD‐associated pain.