Guideline for the management of knee and hip osteoarthritis

Recommendations

Topical analgesics

Guideline for the management of knee and hip osteoarthritis
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  3. Figures and tables
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Pharmacological interventions

Topical analgesics


 

Intervention: Topical nonsteroidal anti-inflammatory drugs (NSAIDs) – Knee and/or hip

Recommendation

We are unable to recommend either for or against the use of topical NSAIDs for people with knee and/or hip osteoarthritis (OA). It might be reasonable to trial topical NSAIDs for a short period then discontinue use if not effective. Clinicians also need to monitor and capture the adverse effects along with its use.

Strength of recommendation

Conditional (neutral) recommendation

Quality of evidence

Moderate

What is it? 

Topical NSAIDs are applied to unbroken skin where there is pain as gels, creams, sprays or plasters. Topical NSAIDs penetrate the skin, enter tissues or joints, and reduce processes that are causing pain in the tissue. Drug levels in the blood with topical NSAIDs are much lower than with the same drug taken by mouth.

Rationale 

The effectiveness of topical NSAID application in OA is variable. Generally, the benefit is small, but the risk of harm is also small. Similar to oral NSAIDs, a judicious trial of topical NSAIDs may be considered as an adjunctive treatment for the short term (several weeks). If unhelpful, topical NSAIDs should be ceased. Regarding adjunctive use, it should be noted that current evidence found that combining a topical NSAID with an oral NSAID confers no additional therapeutic benefit over either agent used alone, but it does increase the number of adverse events.100

Harms 

Usually, adverse events from topical NSAIDs agents are minimal, but there is mild toxicity because of local skin reactions.

Intervention: Topical capsaicin – knee and/ or hip

Recommendation

We suggest not offering topical capsaicin for people with knee OA.

Strength of recommendation

Conditional against recommendation 

Quality of evidence

Low

Recommendation

We are unable to recommend either for or against the use of topical capsaicin for people with hip OA.

Strength of recommendation

Conditional (neutral) recommendation

Quality of evidence

Very low

What is it?

Capsaicin is the neurotoxin of hot chilli peppers. It binds selectively to the vanilloid compound receptor (Transient Receptor Potential Vanilloid 1 [TRPV1]) of type C afferent fibres, and increases P substance in synaptic cleft.101 While first applications of capsaicin are associated with a burning sensation over the applied surface, with continued use, persistent desensitisation and analgesia occurs because of P substance neural depletion, and reversible and selective destruction of primary afferent fibres.101

Rationale 

Evidence from one trial demonstrated that 0.025% of topical capsaicin had small effects of pain relief in people with knee OA (Appendix 5 of the Guideline for the management of knee and hip osteoarthritis: Technical document). It is uncertain whether individuals with multi-joint OA or with relevant comorbidities will benefit from capsaicin. The principle benefit of capsaicin is in neuropathic pain, which is not the major pain source in knee or hip OA. Similar to other topical analgesia, the topical application process is very regime orientated, and local irritation side effects can be detrimental. These issues often outweigh possible benefits to individuals.

Harms 

Mild application site burning was the most common adverse event associated with the topical use of capsaicin (35–100%), but rapidly ameliorates with continuing use. There have been no reports of systemic toxicity with the use of topical capsaicin in OA.

Intervention: Duloxetine – Knee and/or hip

Recommendation

It may be appropriate to offer duloxetine for some people with knee and/or hip OA.

Strength of recommendation

Conditional for recommendation

Quality of evidence

Moderate (knee)
Low (hip

What is it? 

The imbalance of serotonin and norepinephrine systems within the central pain pathways have been implicated in the development and maintenance of central sensitisation, and associated with chronic pain in OA. Duloxetine is a serotonin and norepinephrine reuptake inhibitor (SNRI) with central nervous system activity. Its analgesic efficacy in central pain is putatively related to its influence on descending inhibitory pain pathways. Research has found it has a beneficial effect on pain associated with diabetic neuropathy, fibromyalgia, low back pain and OA.

Rationale 

In the three trials reviewed, significant response and moderate effects in knee pain (standardised mean difference [SMD] 0.43) and function (SMD 0.45) were found over 13–16 weeks at doses of 60/120 mg (Appendix 5 of the Guideline for the management of knee and hip osteoarthritis: Technical document). However, most study participants were also already using NSAIDs and paracetamol. The use of duloxetine for knee OA adjunctively with NSAIDs, thus reducing the usage of NSAIDs and paracetamol, would be clinically useful to reduce adverse events.

In addition, results differed as to whether significant reduction in depression symptoms was needed for analgesic impact. There is no direct randomised controlled trial (RCT) evidence for hip OA; thus, using knee OA data to extrapolate to hip or other OA requires additional caution.

Duloxetine currently does not have an indication via the Therapeutic Goods Administration (TGA) for OA, and should be considered as an investigational medication only. 

Harms 

Among the participants in the three included RCTs, treatment with duloxetine was well tolerated, with the majority of adverse events being of mild or moderate intensity (eg constipation, nausea, hyperhidrosis, cough, myalgia, arthralgia, palpitations). 

Note: subsequent to preparing the grade tables and developing the recommendations, we became aware that one of the studies cited, that by Abou-Raya et al, has been retracted. The recent meta-analysis on duloxetine, which does not include the Abou-Raya study, shows little heterogeneity and remarkable consistency with the effect estimates that we have found.

Intervention: Doxycycline – knee and/or hip

Recommendation

We do not recommend offering doxycycline for people with knee and/or hip OA

Strength of recommendation

Strong against recommendation

Quality of evidence

Low (knee)
Very low (hip)

What is it? 

Doxycycline is a tetracycline-class antibiotic agent. Besides being an antimicrobial agent, it is a metalloproteinase inhibitor, and inhibits the collagenase that cleaves collagen type IX that is present in articular cartilage.104

Rationale 

Preclinical research and earlier human studies indicated doxycycline might be useful in managing symptomatic knee OA. However, current evidence found that doxycycline did not reduce the mean severity of joint pain, although pain scores in both treatment groups were low at baseline and remained low throughout the trial, which may suggest the presence of a floor effect. Despite the small benefit (SMD 0.15 mm) in joint space narrowing, it is outweighed by medication harms (Appendix 5 of the Guideline for the management of knee and hip osteoarthritis: Technical document). 

There is no RCT of doxycycline for hip OA, thus using knee OA data to extrapolate to hip or other OA requires additional caution. Doxycycline currently does not have an indication via the TGA for OA, and should be considered as an investigational medication only. 

Harms 

Adverse events that occurred significantly more frequently in the doxycycline group than the placebo group were restricted to recognised side effects of doxycycline (ie monilial vaginitis, sun sensitivity, nonspecific gastrointestinal symptoms). However, only a small proportion of subjects reporting doxycycline-related side effects discontinued the study medication prematurely. Subjects in the active treatment group reported fewer urinary tract infections, and there was a trend toward fewer upper respiratory tract infections in the doxycycline group than the placebo group.

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