Aromatase inhibitors, joint pain and acupuncture

This blog was first published on 2nd August 2018 on https://blogs.bmj.com/aim/

Effect of Acupuncture on Joint Pain Related to Aromatase Inhibitors Among Women With Early-Stage Breast Cancer – Hershman et al JAMA 2018

woman

A large rigorous and statistically positive trial published in a prestigious general medical journal,[1] and an increasingly familiar conclusion rings out – acupuncture is significantly better than sham, but the difference may not be of clinical significance. This was not the exact conclusion of Hershman et al, but the latter is similar to this common EBM (Evidence-Based Medicine) mantra, perhaps insisted upon by the JAMA editors.

elbow painknee pain

Hershman et al is the biggest trial of acupuncture for joint pain related to the use of aromatase inhibitors in women with breast cancer, and it randomised 226 women in a 2:1:1 split to verum (110), sham (59) or waitlist (57). The acupuncture protocols involved 18 sessions over 12 weeks, with 2 per week for the first 6 weeks. The primary outcome was the worst pain score on the Brief Pain Inventory (BPI-WP) at 6 weeks. The authors chose a clinically meaningful difference on this scale to be 2 points based on the analysis of 11 point Numerical Rating Scales (NRS) performed by Farrar et al.[2]

Farrar-Fig-2-1024x673

But is it a 2-point change from baseline that is clinically relevant, or a 2-point difference between groups. Well the individual patient only knows the change from their own baseline, and the proportion of that change attributed to natural history or expectation in the group mean differences of a trial is irrelevant to the individual.

In the analysis by Farrar et al,[2] the change of 2 points considered to be clinically relevant was measured from baseline. In the present study by Hershman et al,[1] at the primary end point (6 weeks) the mean BPI-WP score in the acupuncture group had dropped 2.05 from baseline, and the percentage of patients with a drop of 2 points or more was 58%. This seems to be clinically relevant to me, but the conclusion reads:

“…the observed improvement was of uncertain clinical importance.”

At all time points the difference between acupuncture and sham control was statistically significant, but the difference did not reach 2 points, and this probably explains their conclusion. At first I assumed it was the JAMA editors that insisted on this conclusion, having seen this done before in a high profile general medical journal.[3] But having checked the protocol of Hershman et al,[1] I see that the authors have made the error of taking Farrar et al’s 2-points’ difference from baseline as a between group difference instead:

Reduction in worst joint pain at 6 weeks between the true acupuncture compared to sham acupuncture and waitlist control groups: A difference of two points in the modified Brief Pain Inventory worst pain score (item #2) has been identified as a clinically meaningful difference.

[From 10.1 of the protocol in supplement 1 of Hershman et al][1]

So I think this must be an error on the part of the authors rather than the insistence of the JAMA editors, but I expect it made it easier to publish the paper in this particular journal, based on its history of accepting negative acupuncture papers.

Whether this particular paper is considered positive or not, the data from it will inform future reviews, and currently these appear to be positive.[4,5]

Before I sign off on this blog, I should comment on the sham control group. It was a superficial penetrating off-point sham, and it did not seem to perform better than waiting list at 6 weeks, with the difference between acupuncture and sham at 0.92 and the difference between acupuncture and waiting list at 0.96. The effect of sham seemed to grow though, since at the 24-week point the difference between acupuncture and sham was only 0.59, and the difference between acupuncture and waiting list was 1.23.

Another pattern to note is that the difference between acupuncture and sham appeared smallest and not statistically significant for the outcome of pain interference, which is probably the closest of the outcomes used to health-related quality of life (HRQoL). Readers of this blog will be familiar with the finding from previous ‘big data’,[6] and my blog on the same.

References

  1. Hershman DL, Unger JM, Greenlee H, et al. Effect of Acupuncture vs Sham Acupuncture or Waitlist Control on Joint Pain Related to Aromatase Inhibitors Among Women With Early-Stage Breast Cancer: A Randomized Clinical Trial. JAMA 2018;320:167–76. doi:10.1001/jama.2018.8907
  2. Farrar JT, Young JP, LaMoreaux L, et al. Clinical importance of changes in chronic pain intensity measured on an 11-point numerical pain rating scale. Pain 2001;94:149–58. doi:10.1016/S0304-3959(01)00349-9
  3. Brinkhaus B, Ortiz M, Witt CM, et al. Acupuncture in Patients With Seasonal Allergic Rhinitis. Ann Intern Med 2013;158:225. doi:10.7326/0003-4819-158-4-201302190-00002
  4. Chen L, Lin C-C, Huang T-W, et al. Effect of acupuncture on aromatase inhibitor-induced arthralgia in patients with breast cancer: A meta-analysis of randomized controlled trials. Breast 2017;33:132–8. doi:10.1016/j.breast.2017.03.015
  5. Halsey EJ, Xing M, Stockley RC. Acupuncture for joint symptoms related to aromatase inhibitor therapy in postmenopausal women with early-stage breast cancer: a narrative review. Acupunct Med 2015;33:188–95. doi:10.1136/acupmed-2014-010735
  6. Saramago P, Woods B, Weatherly H, et al. Methods for network meta-analysis of continuous outcomes using individual patient data: a case study in acupuncture for chronic pain. BMC Med Res Methodol 2016;16:131. doi:10.1186/s12874-016-0224-1

Declaration of interests MC

Breathless…

…a career-defining symptom?

This blog was first published on 18th May 2016 on https://blogs.bmj.com/aim/

The Filshie files – breathlessness

JF
Dr Jacqueline Filshie

Jacky Filshie (JF) has devoted a medical career to symptom management in the cancer suffering population. Her early personal experience of acupuncture needling had a significant impression on her, probably because she happened to have the right genetic complement to maximise the central effects of the technique. Whatever the reason, she was driven to overcome the scepticism of her colleagues in a very prestigious medical institution, and she began to incorporate acupuncture treatment into her routine practice in the cancer pain population.[1] Her enthusiasm for the technique grew, and soon she was trying it on a variety of the more intractable symptoms of her patients. One of these was acute dyspnoea (breathlessness).[2] A key facet of the technique involved gentle periosteal tapping at two sites in the midline on the manubrium of the patient with 36 gauge acupuncture needles (0.16mm diameter). This technique has come to be known as ASAD, which stands for Anxiety, Sickness, And Dyspnoea, or fondly, to reflect JF’s enthusiasm, All Singing And Dancing. In practice this seems to result in a rapid reduction in anxiety and respiratory rate in at least 50% of patients – the figure comes from a conservative and independent palliative care physician who I asked for an honest and confidential opinion some years ago, because without personal experience of using it I admit to having been a little sceptical of JF’s seemingly miraculous results. In 1996 JF noted a marked symptomatic benefit in 70% of her pilot study population with cancer related breathlessness.

Well it is 20 years on since JF’s first published report, and I am pleased to relate that her observation has been confirmed in a subsequent large pragmatic comparative RCT against and in combination with morphine – the conventional treatment for cancer related breathlessness.[3] In fact the responder rate at 4 hours (primary outcome) in the acupuncture group was 76%, compared with 60% in the morphine group and 66% in the combined group (see Figure 3 below from the trial publication).[3] In statistical terms these were not different, but interestingly there was a highly significant benefit in terms of relaxation (secondary outcome) for acupuncture over morphine.

Minchom Fig 3

For those interested, the acupuncture techniques used in the trial are illustrated in the photo below (with thanks to our model Dr Federico Campos): ASAD points; thoracic paraspinals T1 to T5; three trapezius trigger points on each side; and LI4 bilaterally.

Fed breathless

You could always come and she her demonstrate in person at the BMAS Palliative Care Day. Or if you are a BMAS member or an academic associate you can watch her in action from the comfort of your own armchair by logging in to watch the webcast of the BMAS Autumn Meeting 2015 held in the Royal College of Physicians, London.

References

  1. Filshie J. The non-drug treatment of neuralgic and neuropathic pain of malignancy. Cancer Surv 1988;7:161–93.
  2. Filshie J, Penn K, Ashley S, et al. Acupuncture for the relief of cancer-related breathlessness. Palliat Med 1996;10:145–50.
  3. Minchom A, Punwani R, Filshie J, et al. A randomised study comparing the effectiveness of acupuncture or morphine versus the combination for the relief of dyspnoea in patients with advanced non-small cell lung cancer and mesothelioma. Eur J Cancer 2016;61:102–10. doi:10.1016/j.ejca.2016.03.078

Declaration of interests MC