Response to comment by Bhatia Article Swipe

MAKE IMPACT

Chang Liu , Christina Abdel Shaheed , Christopher G. Maher , Andrew J. McLachlan , Jane Latimer , Chung‐Wei Christine Lin · YOU? · · 2020 · Open Access · · DOI: https://doi.org/10.1002/ejp.1577

To the Editor, We thank Dr Bhatia for their commentary (Bhatia, 2020) on our review Efficacy and harms of orally, intramuscularly or intravenously administered glucocorticoids for sciatica: A systematic review and meta-analysis (Abdel Shaheed et al., 2020). Dr Bhatia raised the point that if steroids have a role in the treatment of sciatica what route would be most effective and should studies be done to compare the epidural route (especially transforaminal approach) against oral and other parenteral routes? We agree it will not be easy to answer these questions. Previous studies have evaluated various routes of administration with mixed findings. For patients with radicular symptoms directly related to disc herniation, epidural glucocorticoids can provide small, short-term relief (Pinto, Verwoerd, & Koes, 2017). However, those trials included a heterogenous patient population with regards to the presence of motor and/or sensory deficits. This may explain the small effect observed with epidural administration and raises the question around whether future trials need to consider more strict inclusion criteria. With epidural administration, it is thought the preferred indication is pain radiating below the knee without signs of sensory and/or motor loss. In our review of systemic glucocorticoid administration (oral, intramuscular or intravenous) for people with sciatica, there was wide variability in the timing of treatment. In some trials treatment was initiated within 72-hours from symptom onset, in others several months or years had lapsed before glucocorticoid treatment began. This variability raises another question; when should treatment commence following symptom onset? When does central sensitization take place and would treatment be more complex beyond this point? These considerations may be critical to designing a study which can adequately inform clinical practice. Based on preliminary findings from the review, early treatment may be beneficial, as more promising results came from trials which commenced treatment within 3 months from symptom onset. However, the most promising results, albeit based on low quality evidence, came from a trial of intramuscular administration of methylprednisolone acetate 160 mg within 3 days of symptom onset. Whether this has more to do with formulation, dose, administration route or timing of treatment is unclear. Injectable formulations, for example, methylprednisolone acetate (half-life 12–36 hr) provide more sustained action and can be dosed less frequently than common oral formulations, for example, prednisone. However glucocorticoids administered via the oral, IM or IV routes can all achieve high plasma concentrations. Consideration must also be given to the individual patient's preference. We could not conduct meta-regression to investigate if dose, treatment duration or symptom duration were associated with treatment effect. However, we carried out an analysis based on total cortisone equivalent dose for the immediate term and found no clear evidence of a dose-response relationship. However, this does not preclude the possibility that a relationship may exist. Studies which showed a favourable effect of systemic glucocorticoids administered higher therapeutic doses at initiation. With oral formulations, the tapering regimen shown effective was administered over ~2 weeks; prednisone 60 mg to start, tapered to cessation over 15 days. A similar regimen administered over 9 days provided less clear benefits. This may suggest treatment duration, particularly for oral formulations, may be important in the management of sciatica. There is limited evidence where glucocorticoids administered via the oral, intramuscular, intravenous routes were compared against pharmacological treatments for neuropathic pain (gabapentinoids, antidepressants) or surgery. Furthermore, there is limited evidence from head-to-head trials comparing different routes of administration of glucocorticoids, for example, oral versus epidural. It is reasonable to carry out studies comparing epidural route against oral and other parenteral routes, but we must consider the cost-effectiveness and complexity of epidural injection route. Furthermore, while trials directly comparing routes of administration, and network meta-analysis indirectly comparing routes are possible, blinding of patients and clinicians is not possible and so bias remains problematic. More complex or more expensive treatments may generally be perceived as more effective. In head-to-head trials of injectable (more complex) versus oral (less complex) routes, for example, it may be difficult to ascertain the influence of patient perceptions regarding treatment effectiveness on actual treatment outcomes. These challenges would be difficult to overcome when carrying out head-to head-trials in this context. The author's last point is incidence of adverse effects of steroids and their association with dose-response relationships, if any, need to be established. This is particularly important if the assumption that higher initial doses and longer exposure for example, over ~2 weeks for oral formulations may provide clearer benefit for sciatica. Exposure to glucocorticoids at any therapeutic dose up to 2 weeks is unlikely to cause adrenal suppression (Nicolaides, Pavlaki, Alexandra, & Chrousos, 2018). We found that adverse events were generally mild for all regimens evaluated. For oral administration of prednisolone, there was moderate quality evidence from one study (Goldberg et al., 2015; n = 267) that it may increase the risk of non-serious AEs, for example, dyspepsia, compared with placebo; RR 2.1 (1.4, 3.1). For IM or IV glucocorticoid administration, there was low quality evidence that there may be no difference in AEs compared with placebo; RR (95% CI) 1.6 (0.7, 3.8) or 1.7 (0.5, 6.3) respectively. Due to the limited studies included, we were unable to establish dose-response relationships associated with incidence of adverse effects. Clearly, we need more research in this area. We have taken on the challenge with the OASIS trial (ACTRN12619001716156) of oral prednisolone versus placebo in patients with acute sciatica (ANZCTR, 2019). We encourage funders and researchers to prioritize the key research questions that remain unanswered for managing sciatica.

Type

letter

Language

en

Landing Page

https://doi.org/10.1002/ejp.1577

PDF

https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/ejp.1577

OA Status

bronze

Cited By

1

References

4

Related Works

10

OpenAlex ID

https://openalex.org/W3017083116

Raw OpenAlex JSON

OpenAlex ID

https://openalex.org/W3017083116

Canonical identifier for this work in OpenAlex

DOI

https://doi.org/10.1002/ejp.1577

Digital Object Identifier

Title

Response to comment by Bhatia

Work title

Type

letter

OpenAlex work type

Language

en

Primary language

Publication year

2020

Year of publication

Publication date

2020-04-20

Full publication date if available

Authors

Chang Liu, Christina Abdel Shaheed, Christopher G. Maher, Andrew J. McLachlan, Jane Latimer, Chung‐Wei Christine Lin

List of authors in order

Landing page

https://doi.org/10.1002/ejp.1577

Publisher landing page

PDF URL

https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/ejp.1577

Direct link to full text PDF

Open access

Yes

Whether a free full text is available

OA status

bronze

Open access status per OpenAlex

OA URL

https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/ejp.1577

Direct OA link when available

Concepts

Sciatica, Medicine, Anesthesia, Radicular pain, Population, Surgery, Lumbar, Environmental health

Top concepts (fields/topics) attached by OpenAlex

Cited by

1

Total citation count in OpenAlex

Citations by year (recent)

2022: 1

Per-year citation counts (last 5 years)

References (count)

4

Number of works referenced by this work

Related works (count)

10

Other works algorithmically related by OpenAlex

Full payload