The results of this prospective real-life analysis of patients with CM complement outcomes seen in randomised controlled trials and other real-world analyses, lending additional support for the use of OnabotulinumtoxinA in the management of CM, and providing valuable information on treatment practices and patient characteristics among unselected patients.
In the primary analysis of this patient cohort (254 patients), OnabotulinumtoxinA was shown to significantly reduce the number of headache and migraine days, and increased the number of headache free days versus pre-treatment levels.20 In the current 2-year follow up, these benefits of treatment were shown to continue in a substantial proportion of the patients. Of the cohort of initial responders (N=380) after two cycles of Botox, 45.5% (N=173) were converted to episodic migraine of which the benefit was sustained in 65% (N=112) whilst 35% (N=61) relapsed after an average of 9 months (range 4-24 months).
Few patients became resistant to therapy and reverted to CM while still on treatment (12.3%), others either lost to follow up or stopped due to pregnancy. Importantly, the HIT-6 score was significantly improved at 2 years versus baseline. This persistence in HIT-6 reduction over time indicates a stable and long-term improvement in the impact of headache on patients’ ability to function.
The results of this analysis support previous observations that loss of response to botulinum toxin A for CM after the first year is rare.[i] The outcomes observed also align with those of previous long-term follow ups in real-life clinical scenarios. In a 2-year follow up of 123 patients in the US, it was reported that 67% of patients with CM were still on treatment after 2 years.[ii] In this study, 25% of patients were able to stop treatment and remain free of CM for a minimum of 6 months, and 8% of patients stopped responding to therapy while still on treatment. However, it should be noted that, in this study, the definition of responder was not clearly defined, negative and positive stopping rules were not clear and treatment was funded via insurance reimbursement. In a second US study, the Chronic Migraine OnabotulinumtoxinA Prolonged Efficacy open Label (COMPEL) study, the consistency of the efficacy and the long-term safety and tolerability of OnabotulinumtoxinA for the prevention of headache in 716 patients diagnosed with CM (treated every 12 weeks over 2 years) were analysed.[iii] A significant and sustained benefit of treatment was reported. A limitation of this study was the drop out of nearly half of the patients with reasons not clearly defined. Those who did benefit from treatment were continued on treatment for 2 years. Although the study evaluated long term efficacy, the need for continuation of treatment was not analysed. Finally, in two 3-year follow-ups of treatment of 90 patients in Italy and 65 patients in Greece, respectively, OnabotulinumtoxinA was found to be an effective and well tolerated treatment for CM. [iv],[v] OnabotulinumtoxinA did not show any incoming tolerance and its effectiveness was confirmed to be long-lasting, generating stable improvements in headache symptoms and patients’ quality of life.25
The degree of analgesic use before and after treatment was studied and reported earlier. The median number of painkiller days before treatment was 12 (interquartile range of 6-22). This was reduced to 7 days (range 2–13) after treatment. The frequent or regular use of analgesics and anti-migraine drugs can make headache more frequent and induce the transformation of episodic to CM.[vi] Medication overuse was highly prevalent in the patient population included in this prospective analysis, with 54% of patients overusing various analgesics (triptans and/or other analgesics [paracetamol, nonsteroidal anti-inflammatory drugs and opioids]). OnabotulinumtoxinA offered an effective prophylactic treatment option in these patients and the results of the current analysis confirmed the outcomes from earlier studies that demonstrated that OnabotulinumtoxinA was effective in individuals regardless of medication overuse at baseline.25,[vii],[viii],[ix]
The current prospective analysis provides an insight into the long-term outcomes in 655 patients diagnosed with CM prophylactically treated with OnabotulinumtoxinA in a real-life clinical setting that measured not only treatment response using defined responder criteria, but also analysed the frequency of headache days and the severity of the headaches. The prospective analysis also provided important insights into the sustainability of the response to treatment and the degree of resistance to treatment over the long term. As with the primary patient population, the patient cohort in this analysis is believed to be representative of patients seen in daily clinical practice at an average tertiary headache centre in the UK and is concordant with previous observations in real-life long-term clinical studies assessing the efficacy of OnabotulinumtoxinA for the treatment of CM.[x]
The strength of this prospective analysis was the large sample size that was representative of the patients with CM typically seen in daily clinical practice in a tertiary headache centre of UK. However, as with any prospective real-life analysis, there was a risk of confounding bias and lack of randomisation, and the lack of a control group meant it was not possible to quantify a placebo effect. The second limitation is that this is a single centre study, which may reflect practice bias of the clinician in the centre. The third limitation is that the study was conducted in the UK where treatment is funded centrally by the NHS and start and stopping rules of the treatment may differ from other countries where limitations and reimbursement rules may be different. The 2-year data does not include patients that could have relapsed or become resistant beyond 2 years and may have had a different outcome. The adverse effects of the toxin was only evaluated during the second cycle, although we believe that this would not have been higher subsequently as none of the patients stopped treatment due to adverse effects and the number of patients that were lost to follow up were very small.