Received: 9 December 2022
|
Accepted: 11 March 2023
DOI: 10.1002/jor.25549
RESEARCH ARTICLE
Topicalnonsteroidalanti‐inflammatorydrugsfor
managementofosteoarthritispain:Aconsensus
recommendation
Joon‐Kiong Lee
1
| Azlina A. Abbas
2
| Tien‐Eang Cheah
3
|
Ruslan Nazaruddin Simanjuntak
4
| Sargunan Sockalingam
5
| Sharifah Roohi
6
1
Beacon Hospital, Petaling Jaya, Malaysia
2
National Orthopaedic Centre of Excellence
for Research and Learning (NOCERAL),
Universiti Malaya, Kuala Lumpur, Malaysia
3
Rheumatology Unit, Pantai Hospital, Kuala
Lumpur, Malaysia
4
ALTY Hospital, Kuala Lumpur, Malaysia
5
Rheumatology Unit, Universiti Malaya
Medical Centre, Kuala Lumpur, Malaysia
6
Hand & Upper Limb Centre, Pantai Hospital,
Kuala Lumpur, Malaysia
Correspondence
Joon‐Kiong Lee, Beacon Hospital, No. 1, Jalan
215, Off Jalan Templer, Section 51, 46050
Petaling Jaya, Malaysia.
Email: osteoporosis_jklee@yahoo.com
Funding information
Hoe Pharmaceutical Sdn Bhd
Abstract
Osteoarthritis (OA) contributes to significant medical and socioeconomic burden in
many populations. Its prevalence is expected to rise continuously owing to the
combined effects of aging and increase in risk factors, including obesity, physical
inactivity, and joint injuries. Pain is a hallmark presentation of OA. Topical
nonsteroidal anti‐inflammatory drugs (NSAIDs) are recommended by many
international guidelines as an early treatment option of the management of
osteoarthritic pain. However, the use of topical NSAIDs remains low in Malaysia
and appears not to be a preferred agent in managing OA pain by prescribers. There is
also limited guidance from local medical bodies on the use of topical NSAIDs to
manage OA pain. This consensus recommendation is intended to serve as a practical
guide for healthcare practitioners on the use of topical NSAIDs in the management
of OA pain. Eight statements and recommendations were finalized covering the
areas of OA burden, topical NSAIDs formulations, safety and efficacy of topical
NSAIDs, and patient education. Robust evidence is available to support the efficacy
and safety of topical NSAIDs, with its benefits further strengthened by ease of use
and access. Taking these into consideration, we recommend that healthcare
practitioners advocate for the early use of topical NSAIDs over oral NSAIDs for
mild‐to‐moderate OA pain, while engaging in a shared decision‐making process with
patients for optimal clinical outcomes.
KEYWORDS
consensus development, nonsteroidal anti‐inflammatory drugs, osteoarthritis,
pain management, topical administration
J Orthop Res. 2023;1–9. wileyonlinelibrary.com/journal/jor | 1
This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium,
provided the original work is properly cited.
? 2023 The Authors. Journal of Orthopaedic Research
?
published by Wiley Periodicals LLC on behalf of Orthopaedic Research Society.
1 | INTRODUCTION
Osteoarthritis (OA) is the most common form of arthritis, affecting
one in three people over the age of 65, with more women affected
than men.
1,2
It is estimated that 500 million people or 7% of the
global population are living with the condition.
2
Between 1990 and
2019, the number of people affected by OA globally rose by 48%.
2,3
This rise in OA prevalence is partly due to the increasing occurrences
of OA risk factors, including obesity, physical inactivity, and joint
injury.
4
OA is characterized by structural changes in the articular
cartilage, subchondral bone, ligaments, capsule, synovial membrane,
and periarticular muscles.
5,6
Pain is the dominant symptom that leads
to functional limitations, poor quality sleep, fatigue, depressed mood,
and loss of independence.
4,7
OA is a debilitating disease. It accounts
for 2.4% of all years lived with disability (YLD).
1,8
Between 1990 and
2013, a 75% increase was seen in OA‐related YLDs worldwide such
that currently, OA is the third most rapidly rising condition associated
with disability after diabetes and dementia.
8
It is a leading cause of
disability in older adults and the primary indication for joint
replacement surgery.
4
However, surgery should be reserved for
cases in which all appropriate, less invasive options that have been
delivered for a reasonable period have not provided adequate
symptom relief.
OA can affect any joint, but typically affected areas are the hip,
knees, hands, and spine. Clinically, the knee is the most common site
of OA, followed by the hand and hip.
9,10
Data also indicates a much
higher prevalence of radiographic OA than symptomatic OA, and
knee and hand OA as compared to hip OA.
11
Knee OA accounts for
approximately 85% of the OA burden worldwide. It is also under‐
diagnosed and under‐treated.
12
Patients with OA report that their
concerns are downplayed by health practitioners.
13
Therapeutic
nihilism may affect patients and practitioners, with misperceptions
that OA is an inevitable part of aging and that there are no effective
treatments.
14
Many manage it by avoiding physical activities that
exacerbate their pain, which is problematic as physical activity is at
present the most effective and safe nonsurgical treatment for hip and
knee OA.
4
Current healthcare approaches can swing from neglect of
core treatments, such as exercise, weight loss, and education, to use
of expensive, unproven therapies for late‐stage disease.
14–16
Despite its considerable personal, economic, and societal toll, OA
is generally neglected.
14
The condition does not feature in global
strategic plans for noncommunicable diseases, yet OA commonly
coexists with heart disease, diabetes, and mental health problems and
can worsen the morbidity and mortality associated with these
conditions.
14,17
Recently, a group of Malaysian experts developed a Delphi
consensus on managing knee OA, with recommendations advocating
an algorithmic approach in the management of patients living with
the condition.
18
There is increasing evidence on the benefits of
topical NSAIDs and recommendations for its use in managing OA by
various international bodies.
19–29
However, the use of topical
NSAIDs remains low in Malaysia. There is also limited guidance from
local medical bodies on the use of topical NSAIDs to manage OA
pain. Available clinical guidelines in Malaysia provide only brief and
very general recommendations with no clear guidance on the
mechanism of action, efficacy, and safety.
30
A clear gap is therefore
present in the efforts to promote appropriate and judicious use of
topical NSAIDs in clinical practice.
This consensus recommendation is intended to serve as a
practical guide for healthcare practitioners in Malaysia on the use
of topical NSAIDs in the management of OA pain; however, it is also
relevant to clinicians and pharmacists outside Malaysia. The
recommendations are aimed at informing healthcare practitioners
about the proper use of topical NSAIDs based on current evidence on
pharmacology, efficacy, and safety for the management of OA pain.
2 | METHODS
Members of the working group include orthopedic surgeons and
rheumatologists who are key opinion leaders and researchers in
Malaysia. Six members were invited to the first meeting to discuss
issues on the unmet needs in OA pharmacological treatment,
especially in the context of the use of topical NSAIDs based on
clinical experience and current literature. Points raised during the
meeting were then drafted into recommendation statements. These
statements were judged to be the most relevant and beneficial to
healthcare professionals in their clinical practice based on the current
assessment of knowledge gaps on topical NSAIDs in OA pain
management.
Literature to support or refute the statements were gathered
based on published evidence. This was done through a search of
medical literature in the English language using PubMed, Scopus, and
Google Scholar databases. Search terms included: “topical NSAIDs,”
“osteoarthritis,”“guidelines,”“recommendation”“randomised con-
trolled trials,”“systematic review,” and “meta‐analyses.” Reference
lists of retrieved articles were searched.
The recommendations proposed at the meeting were refined
based on the evidence gathered. The strength of the recommenda-
tions was based on the three‐level rating system adapted from the
Scottish Intercollegiate Guidelines Network Grading System:
Grade A: At least one meta‐analysis, systematic review, or
randomized‐controlled trial (RCT), or evidence rated as good and
directly applicable to the target population.
Grade B: Evidence from well‐conducted clinical trials, directly
applicable to the target population and demonstrating overall
consistency of results; or evidence extrapolated from meta‐analysis,
systematic review, or RCT.
Grade C: Evidence from expert committee reports, or opinions
and/or clinical experiences of respected authorities; indicates
absence of directly applicable clinical studies of good quality.
All group members were invited to provide their feedback
independently, after which a second meeting was called to review the
recommended revisions by the group members. The statements and
recommendations were further revised based on the feedback and
2
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justifications received from all members. A unanimous consensus was
achieved among all members on the final statements and recommen-
dations presented here.
3 | RESULTS
Panel statements are listed inTable 1.
Statement 1: OA is a substantial health problem with prevalence
expected to continuously rise placing a significant burden on national
economic and healthcare systems.
Global prevalence of OA is high and is expected to continue
increasing in the coming years. OA represents a substantial and
increasing health burden with notable implications for the individuals
affected and healthcare systems, as well as wider socioeconomic
costs. Combined effects of aging and increasing obesity in the global
population, along with increasing numbers of joint injuries is
increasing the prevalence of OA globally.
11
Worldwide data show that a significant proportion of women
above the age of 65 will have knee OA.
31,32
Consistent with these
global trends, the prevalence of OA in Malaysia is also currently high
and is expected to rise with an increasingly aging population. Data
from 2019 show that 30.8% of population aged 55 and above in
Kuala Lumpur have knee OA, with the prevalence highest among
Malays, followed by Indians and Chinese.
33
In 2019, the percentage
of Malaysians aged ≥65 was estimated to be 6.7%; by 2040, this is
expected to significantly increase to 14.5%.
34,35
Additionally, rising
obesity and noncommunicable disease rates also contribute to an
expected increase in OA prevalence among Malaysians.
36
Beyond medical costs of managing OA, which was estimated to
account for 1%–2.5% of the gross domestic product of various
countries,
37
there are also indirect costs attributed to OA. These
include costs due to work loss and premature retirement as well as
personal costs for patients, such as loss of income and subsequent
reductions in personal savings that greatly surpass the direct
healthcare costs.
38,39
Panel recommendation 1: Owing to the expected continuous rise
in OA prevalence and its implications to healthcare and personal
costs, greater urgency is needed in developing and promoting
sustainable approaches to treat OA pain.
Grade of recommendation:A
Statement 2: Use of topical NSAIDs remain low in Malaysia
compared with oral NSAIDs despite strong evidence on efficacy and
recommendations by international guidelines.
First‐line treatment for OA include nonpharmacological methods
such as education and self‐management, exercise, weight loss for
those who are overweight/obese, and walking aids as needed.
11,40
Patient education encompasses various aspects of information, such
as importance of regular physical activity as well as individualized
exercise and weight loss plans if necessary.
41
It is also important to
educate patients on the role of surgery only as a later‐line approach
and information about the disease, including pathogenesis, symp-
toms, and diagnostic methods.
Pain medications are also recommended by guidelines, with
paracetamol and NSAIDs being the most frequently recommended
agents for mild‐to‐moderate pain.
18,23–30,40
While oral NSAIDs have
been shown to result in clinically meaningful improvement in both
pain and function, concerns about safety, particularly relating to
gastrointestinal and cardiovascular events raise important considera-
tions in selecting the preparation and dose for individual patients.
Oral NSAIDs are preferably restricted to short‐term use at the
smallest dose possible.
11,24,26,30
Topical NSAIDs are also recom-
mended for pain relief in OA, with no serious gastrointestinal
or renal adverse events observed in trials or in the general
population.
19,20,23,25,27–30,42
Other pharmacological agents used for
OA pain management include intra‐articular hyaluronans and
prescription‐grade crystalline glucosamine sulfate or chondroitin for
knee OA.
18,23–26,28
The use of intra‐articular corticosteroids remains
controversial. It was not universally recommended by all guidelines as
current evidence remains inconclusive and due to the potential harm
from repeated injections.
18,23–25,29,30,40
Knee braces, heel wedges,
acupuncture, and glucosamine and chondroitin nutraceuticals are
typically not recommended by guidelines due to a lack of evidence on
their efficacy in pain relief.
11,26,27,29,40
Despite strong evidence on the efficacy and safety of topical
NSAIDs for OA pain management, market data show that the use of
topical NSAIDs in Malaysia remains significantly lower than oral
NSAIDs. Between 2017 and 2020, topical NSAIDs were reported to
range between 12.9% and 14.4% of the total NSAIDs market in
Malaysia.
43
In contrast, topical NSAIDs comprise 33.6%–36.4% of
TABLE 1 Panel statements on the use of topical NSAIDs to
manage OA pain.
Statement 1: OA is a substantial health problem with prevalence
expected to continuously rise placing a significant burden on
national economic and healthcare systems.
Statement 2: Use of topical NSAIDs remains low in Malaysia compared
with oral NSAIDs despite strong evidence on efficacy and
recommendations by international guidelines.
Statement 3: Topical NSAIDs are available in a variety of preparations
and formulations with distinct modes of delivery that are suitable
for the treatment of mild‐to‐moderate OA pain.
Statement 4: Topical NSAIDs at recommended dosage have
comparable efficacy with oral NSAIDs for mild‐to‐moderate
osteoarthritic pain relief.
Statement 5: Topical NSAIDs can provide effective relief for some
patients with OA affecting more superficial sites of pain.
Statement 6: Topical NSAIDs have the advantage of local, enhanced
drug delivery to affected tissues with reduced systemic absorption.
Statement 7: Patient education is important to encourage the wider use
of topical NSAIDs for mild‐to‐moderate OA pain.
Statement 8: Topical NSAIDs help to reduce polypharmacy, especially
among older patients with OA and with multiple comorbidities.
Abbreviations: NSAID, nonsteroidal anti‐inflammatory drugs; OA,
osteoarthritis.
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the USA NSAID market and 63.4%–67.9% of the Japan NSAID
market during the same period.
43
Use of topical NSAIDs was also low
at an average of 9.9% of total NSAID market in Thailand between
2017 and 2020.
43
These data clearly indicate that the use of topical
NSAIDs is under‐recognized and underutilized in Malaysia and
neighboring Thailand despite evidence showing it to be clinically
effective, safe, and cost‐efficient.
Panel recommendation 2: Awareness on the benefits of topical
NSAIDs must be improved among healthcare professionals and
patients to promote utilization of topical NSAIDs for mild‐to‐
moderate OA pain.
Grade of recommendation:A
Statement 3: Topical NSAIDs are available in a variety of
preparations and formulations with distinct modes of delivery that are
suitable for the treatment of mild‐to‐moderate OA pain.
Topical NSAID formulations available worldwide include
salicylates (acetylsalicylic acid), propionic acid derivatives (ibu-
profen,suprofen,ketoprofen,flurbiprofen,andesflurbiprofen),
acetic acid derivatives (diclofenac, indomethacin, and ketorolac),
enolic acid derivatives (piroxicam), anthranilic acid derivatives
(mefenamic acid and meclofenamic acid), and selective
cyclooxygenase‐2(COX‐2) inhibitors (celecoxib, etoricoxib, and
valdecoxib). The therapeutic effect of topical NSAIDs depends on
the drug''s ability to penetrate and permeate the skin and
subsequently inhibit COX isoform responsible for pain and
inflammation.
44
Different active ingredients have different
degrees of skin penetration.
Topical NSAIDs are also available in a wide variety of
formulations, including gel, foam, cream, ointment, spray, and
patch/plaster.
44
Formulation is also another crucial factor for good
skin penetration. A balance between lipid and aqueous solubility is
needed to optimize penetration, and use of prodrug esters has
been suggested as a way of enhancing permeability.
45
Studies have
shown that creams are generally less effective than gels or sprays,
but newer formulations such as microemulsions may have greater
potential.
46
A systematic review found that the diclofenac patch exhibited
the largest effect on pain, above that of diclofenac gel and
solutions.
42
The authors attributed this potentially to the constant
and continuous delivery of the active ingredient to the affected area
via an occlusive bandage and slow release of the drug when
compared with gels and solutions.
42
It could also be due to the
higher contextual effects of patches than creams or gels. In another
systematic review, gel formulations of diclofenac, ibuprofen, and
ketoprofen as well as some diclofenac patches were shown to
provide the best effects.
45
Panel recommendation 3: Carefully consider the effectiveness of
different preparations and formulations of topical NSAIDs when
selecting suitable therapeutic agents for individual patients.
Grade of recommendation:A
Statement 4: Topical NSAIDs at recommended dosage have
comparable efficacy with oral NSAIDs for mild‐to‐moderate osteo-
arthritic pain relief.
Multiple RCTs and meta‐analyses have provided robust evidence
on the efficacy of topical NSAIDs.
42,45,47,48
These studies have
demonstrated that topical NSAIDs provide at least equivalent
analgesia, improvement in physical function, and reduction of
stiffness compared with oral NSAIDs in OA.
Most data available on the effectiveness of topical NSAIDs in OA
are on topical diclofenac and ketoprofen. A Cochrane systematic
review in 2012 found no difference in efficacy between topical and
oral NSAIDs for reducing pain due to chronic musculoskeletal
conditions.
49
Subsequently, a 2016 Cochrane systematic review
including five studies (877 participants) comparing topical NSAIDs
(diclofenac, ketoprofen, piroxicam) with oral NSAIDs (celecoxib,
diclofenac, ibuprofen) in adults mainly with knee OA reported that
55% and 54% of patients achieved meaningful pain relief (pain
reduction by 50%) with a topical NSAID and oral NSAID, respec-
tively.
45
According to the same review, 60% of patients reported pain
reduction by 50% following topical application of diclofenac or
ketoprofen.
45
Another systematic review reported the effectiveness of
diclofenac (5995 participants) and ketoprofen (2573 participants).
In patients with knee or hand OA, the numbers needed to treat (NNT)
for ≥50% reduction of pain intensity at 6–12 weeks after treatment
initiation are 9.5 for any topical formulation of diclofenac and 6.9 for
ketoprofen gel.
50
While the NNT is relatively large, it is still promising
as patients who do derive benefits from a topical NSAID may not
need to consider the use of other interventions with a worse adverse
effect profile.
21
Topical NSAIDs are also expected to be similarly
effective for other OA conditions.
21
A recent systematic review comparing the effects of five major
drug categories in the treatment of OA pain found that topical
NSAIDs produced greater relative changes in pain than oral
NSAIDs.
51
The authors concluded that considering topical NSAIDs
have a lower serious adverse event rate compared to oral NSAIDs, it
may be prudent to use topical formulations before starting oral
medications for OA pain.
In another review of analgesics for the management of knee or
finger OA, seven out of the eight identified studies showed no
statistically significant differences in efficacy between topical
NSAIDs (diclofenac, ibuprofen, ketoprofen, and piroxicam) and oral
NSAIDs (celecoxib, diclofenac, and ibuprofen).
52
Additionally, an RCT
and patient preference study reported that at 12 months, the clinical
outcomes were equivalent between patients given initial advice to
use topical ibuprofen and those given advice to use oral ibuprofen for
chronic knee pain relief.
53
An analysis of six studies involving more than 3000 patients with
various acute and chronic musculoskeletal injuries, including OA
showed that results with topical and oral NSAIDs were statistically
superior to those with placebo for treatment of both acute and
chronic injury.
54
All head‐to‐head comparisons between topical and
oral NSAIDs showed comparable efficacy between the two for
treatment of acute and chronic injuries.
55
Separately, three RCTs
have directly compared topical diclofenac with either oral diclofenac
or ibuprofen.
54,56,57
All three trials found the topical agent to provide
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at least equivalent relief of OA pain and other symptoms as the oral
agents.
Panel recommendation 4: Topical NSAIDs should be prioritized
over oral NSAIDs for mild‐to‐moderate OA pain, given robust
evidence on the comparable efficacy.
Grade of recommendation:A
Statement 5: Topical NSAIDs can provide effective relief for some
patients with OA affecting more superficial sites of pain.
Topical NSAIDs are formulated for direct application to the site
of pain with the aim of producing a local pain‐relieving effect while
avoiding the body‐wide distribution of the drug at physiologically
active levels.
44,58
These agents act precisely where they are needed
without first having to be absorbed via the stomach and then
transported in the blood.
44,58
The sites of action for topical agents
are the soft tissues and peripheral nerves underlying the site of
application.
44,58
They likely provide relief by reducing ectopic
discharges from superficial somatic nerves.
44
The topical method of application, therefore, act most
effectivelyonmoresuperficialsitesofpainsuchasinOAjoints
in the knees, finger and hand, ankle and shoulder.
45
These are
joints that are close to the surface of the skin. They would not, for
example, be indicated for the treatment of deeper seated joints,
such as hips or spine or for deep visceral pain or headaches.
45
Topical NSAIDs are also preferred for people with only a few
painful joints to prevent the risk of exceeding the recommended
dosage when applied at too many sites.
Panel recommendation 5:Topical NSAIDs should be used for mild‐
to‐moderate OA pain affecting superficial sites.
Grade of recommendation:A
Statement 6: Topical NSAIDs has the advantage of local, enhanced
drug delivery to affected tissues with reduced systemic absorption.
Topical therapies mainly act by reaching high concentrations in
the structures of joints, with only a small amount entering the
systemic circulation. Plasma levels after topical administration have
been reported to range between 0.2% and 8% of those achieved
after oral administration.
44
While having only a small amount of the
drug in the systemic circulation is a desirable trait to minimize any
side effects in the circulatory and other organ systems, it is equally
important to have sufficient concentrations of the active ingredient
reaching the joint to exert its anti‐inflammatory effect. Topical
NSAIDs need to be able to penetrate the skin and permeate to the
target areas in sufficient quantities to exert a therapeutic effect. The
measurement of drug concentrations at the site of action is
postulated to be an indicator of their likely efficacy.
59
The pharmacological action of topical drugs relies on penetration
through the stratum corneum and permeation into the lower layers of
the skin.
44
The stratum corneum functions to protect the more
delicate structures beneath it and therefore can be very difficult to
penetrate passively. To overcome this, topically applied drugs may
have a depot effect, such that they accumulate for a prolonged time
in the stratum corneum, epidermis, dermis, and subcutaneous fatty
tissue to form a reservoir that supplies a sustained release of the drug
into surrounding tissues.
59
Several factors affect the penetration of the drug through the
stratum corneum and permeation to the underlying tissues. An ideal
topical drug would have a small molecular size, have both lipophilic
and hydrophilic properties, be acidic, and have good solubility of the
vehicle used.
59
Additionally, the site and method of application and
protein concentrations in the site of pain also affect the optimal
penetration of a topical drug. Patch and plaster formulations provide
additional benefit to traditional topical gels and creams as they can
offer continuous and increased absorption.
44,59
Penetration of drugs
may also be significantly improved through the use of ultrasound and
iontophoresis.
60
Generally, the concentration of NSAIDs after topical administra-
tion in the joint cartilage and in the meniscus is 4–7 times higher
compared to that after oral administration of NSAID.
61
A systematic
review assessing topical diclofenac in OA reported that topical
diclofenac penetrated through the skin and permeated to the target
tissues in appreciable amounts, with different concentrations within
the knee.
59
Concentration was generally higher in synovial tissue
than in synovial fluid. There is, however, limited data on the
concentrations of diclofenac in the joint to draw any conclusions.
Nevertheless, it is known that topical diclofenac is effective with a
lower rate of systemic adverse events observed compared with oral
diclofenac.
Panel recommendation 6: Topical NSAIDs are preferred over oral
NSAIDs due to fewer systemic adverse events while providing
adequate local drug concentration at the target tissue for pain relief.
Grade of recommendation:A
Statement 7: Patient education is important to encourage wider use
of topical NSAIDs for mild‐to‐moderate OA pain.
Decision‐making on the choice of treatment in managing OA
should take on a collaborative approach between healthcare
professional and patient, taking into account both parties'' beliefs
about clinical benefit, adverse effects, preferences, and costs.
Understanding how patients'' beliefs determine their preferences
for treatment might improve the quality of this shared decision‐
making process and treatment success. Studies have found that
factors influencing treatment choices by patients with arthritis
include relief of symptoms, the occurrence of adverse effects, and
the availability of alternative treatments.
62–64
To further expand on these findings, a study was done to
examine the factors influencing the study participants in making their
choice of either using topical or oral ibuprofen for their knee pain.
65
The investigators found that patients with transient pain considered
their pain less degenerative and preferred topical preparations.
Topical analgesics were also considered to have a localized rather
than a generalized effect. Patients had clear beliefs that topical
preparations would not affect the rest of the body and that it would
take effect more quickly. They also assumed that topical preparations
have a lower dose of the active ingredient and therefore less toxic.
Patients who believed that their treatment was benefitting them
were willing to tolerate some mild adverse effects, such as a rash,
fatigue, change in bowel habits, and occasional upset stomach.
65
Topical preparations were viewed as safe because they did not enter
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the circulatory system in the same way oral medications do. Patients
also wanted a medication regimen that was practical for daily use and
lifestyle. Others considered oral medications as time‐consuming and
messy. Those who chose topical preparations also considered the
amount of other medication or tablets that they are already taking.
These findings were also seen in another similar study among older
people where it was shown that patient preference for medication
type was influenced by previous experience of medication, other
illness, pain elsewhere, anecdotes, convenience, severity of pain, and
perceived degree of joint degeneration.
66
Importantly, lack of
understanding about knee pain and the action of medication led to
increased tolerance of symptoms.
66
In another Japanese study evaluating patients'' desired charac-
teristics of NSAID topical plasters, analgesic efficacy, including
analgesic strength, length of action, and early onset of action,
followed by avoiding skin irritation and low medication cost were the
characteristics most frequently reported as desirable by patients.
67
Studies have found that increasing patients'' knowledge through
education about the causes of knee pain, treatment mode of action,
and adverse effects improves both adherence and informed
choice.
68,69
It is therefore important for healthcare professionals to
engage patients in a shared decision‐making process to encourage
the use of topical NSAIDs among suitable patients and to promote
treatment adherence. Equally important is to correct any misunder-
standing about disease pathogenesis and medication mechanism of
action so that major adverse effects are alleviated.
Panel recommendation 7: Healthcare professionals should discuss
with patients about efficacy, availability, and applicability of topical
NSAIDs to encourage them to choose the treatment modality.
Grade of recommendation:A
Statement 8: Topical NSAIDs help to reduce polypharmacy,
especially among older patients with OA and with multiple comorbidities.
The option of topical NSAIDs is especially welcomed for OA as it
is a condition predominantly affecting the older population, who is at
higher risk of experiencing the side effects of prolonged NSAID use
either owing to multiple comorbidities or polypharmacy augmenting
that effect. The typical OA patient is an elderly person with multiple
medical problems and taking several medication who will require
long‐term treatment. This population is especially vulnerable to drug
toxicity due to factors such as poor treatment adherence, nutritional
insufficiency, altered pharmacokinetics, end‐organ responsiveness,
and the increased likelihood for drug–drug interactions arising from
polypharmacy for various comorbidities.
70
The reduced side effect
potential with topical NSAIDs is indeed a favorable characteristic,
particularly for this population.
Commonly reported toxicities attributed to oral NSAID use
include morbidity and mortality from gastrointestinal events.
71,72
Other significant side‐effects of oral NSAIDs include renal insuffi-
ciency, hypertension, leg edema, and exacerbation of heart failure
and an increased risk of cardiovascular events.
72
The use of topical NSAIDs may have a treatment‐sparing effect
on the use of oral NSAIDs in moderate‐to‐severe rheumatic diseases.
A real‐world study including more than 1200 patients with OA
showed that an average 40% reduction in the required dose of oral
NSAIDs was achieved with the addition of topical etofenamate.
20,73
This lead to a 46% improvement in pain and 34% improvement in
function while the lowering of the oral NSAID dose led to a
significant reduction in the adverse effects reported, particularly a
>20% reduction in adverse effects of the gastrointestinal tract.
20,73
As the presence of other illness or pain as well as the amount of
other medication or tablets used are important considerations that
patients take into account when choosing their preferred medication,
topical NSAIDs provide an appropriate and acceptable option for
patients whom polypharmacy and multiple comorbidities are
concerns.
Panel recommendation 8: Healthcare professionals should edu-
cate patients on the benefit of topical NSAIDs in potentially reducing
polypharmacy.
Grade of recommendation:B
4 | CONCLUSION
This publication presents evidence‐based consensus recommenda-
tions on the use of topical NSAIDs for the management of mild‐to‐
moderate OA pain. In agreement with major OA treatment guidelines,
the panel supports the use of topical NSAIDs over oral NSAIDs as
first‐line treatment of mild‐to‐moderate OA pain. This recommenda-
tion is mainly driven by the findings of numerous trials that topical
NSAIDs have comparable efficacy but a lower risk of systemic side
effects to oral NSAIDs. Patient education is important in the shared
decision‐making process between the healthcare professional and
patient in choosing the most appropriate preparation and formula-
tion. This in turn improves treatment adherence thus reducing pain,
leading to an improvement in patients'' quality of life.
AUTHOR CONTRIBUTIONS
All authors contributed to the discussion contained in the article, and
have read and approved the final submitted manuscript.
ACKNOWLEDGMENTS
The authors thank Hoe Pharmaceutical Sdn Bhd, a subsidiary of
Taisho Pharmaceutical Pte Ltd. for financial support of publication
costs and medical writing, and for providing administrative support.
Medical writing assistance was provided by Zerorange Healthcare
Sdn Bhd. All organizations had no role in the study design, data
collection, analysis, or decisions and recommendations made by the
authors in this manuscript.
CONFLICT OF INTEREST STATEMENT
Sargunan Sockalingam declares receipt of speaker fees and advisory
board membership from AstraZeneca, Zuellig Pharma, and Pfizer.
Sharifah Roohi declares payment for the development of educa-
tional/clinical guidelines from Hoe Pharmaceutical. Joon‐Kiong Lee,
Azlina Amir Abbas, Tien‐Eang Cheah, and G. Ruslan Nazaruddin
Simanjuntak declares no conflicts of interest.
6
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LEE ET AL.
1554527x, 0, Downloaded from https://onlinelibrary.wiley.com/doi/10.1002/jor.25549 by CochraneChina, Wiley Online Library on [30/03/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
ORCID
Joon‐Kiong Lee http://orcid.org/0000-0002-4215-1689
Sharifah Roohi https://orcid.org/0000-0003-2068-4238
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How to cite this article: Lee J‐K, Abbas AA, Cheah T‐E,
Simanjuntak RN, Sockalingam S, Roohi S. Topical nonsteroidal
anti‐inflammatory drugs for management of osteoarthritis
pain: a consensus recommendation. J Orthop Res. 2023;1‐9.
doi:10.1002/jor.25549
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