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Opinion remains divided regarding how aggressively MS should be treated. Some neurologists believe in the “treat early, treat aggressively” approach, whilst others prefer to “save” HE therapies until the more traditional platform therapies have failed.
The advent of injectable interferon therapy in the early 1990s paved the way for disease modifying treatment of multiple sclerosis (MS) patients.
These “platform injectable therapies” have traditionally dominated the relapsing-remitting MS (RRMS) treatment landscape ever since. Prior to this, the only option for patients with an active or highly active MS profile was Tysabri, the intravenously-administered monoclonal antibody (mAb); this brand experienced its own issues after Biogen removed it from the market in 2006 due to serious adverse events but was re-introduced in 2008. It was not until 2010 that another high efficacy (HE) option entered the fray - Novartis’ orally administered Gilenya. By mid-2018, two additional mAbs (Lemtrada and Ocrevus) and another HE oral therapy, Mavenclad, had further expanded neurologists’ armamentarium for the treatment of active and highly active RRMS.
Whilst on face value this expansion of the disease modifying treatment options may be considered beneficial to neurologists and patients alike, opinion remains divided regarding how aggressively MS should be treated. Some neurologists believe in the “treat early, treat aggressively” approach, whilst others prefer to “save” HE therapies until the more traditional platform therapies have failed.1There is also the trade-off between the disease control benefits of treating early with one of these HE disease-modifying therapies (DMTs) vs. a higher risk of an adverse event occurring in a patient.2
So how big is this divide in opinion, and how has it changed with the increasing number of HE therapies now available to neurologists? We have drawn insights from Ipsos’ syndicated Multiple Sclerosis Therapy Monitors in the EU5 and US to shed light on this subject.
When focusing on EU5 RRMS patients who initiated their 1st line of DMT within twelve months of their most recent consultation, 14% of our reported patient sample initiated onto a “high-efficacy” option in Q4 2015. In Q4 2018, however, 27% of this patient cohort were receiving a HE therapy.3 A similar scenario is seen amongst the equivalent group of patients in the US; 17% were in receipt of a HE therapy in Q4 2015, compared to 33% in Q4 2018.4
This trend is seen again in the use of mAbs in this patient setting. In the EU5, the percentage of these reported sample patients initiating onto either Tysabri or Lemtrada in Q4 2015 was 9% vs 16% in Q4 2018 (the latter timepoint including Ocrevus). In the US, the jump was from 3% in Q4 2015 to 18% in Q4 2018.
This would suggest a growing propensity amongst neurologists in both regions to use these high-efficacy DMTs earlier in the treatment paradigm (indeed, as the very first DMT given). A closer look at the EU5 cohort sees a jump in the newly initiated patients receiving a HE DMT between Q417 and Q418 specifically (18% vs 27%). This may point to the fact that the approval of Mavenclad in Q3 2017 and Ocrevus in early 2018 – as well as an increase in usage of the more established Gilenya – has helped expand neurologist comfort with this particular treatment notion, as all three of these agents have shown significant growth within this timeframe.
No, not necessarily. The proportion of RRMS patients in our reported sample in the EU5 in Q4 2015 who initiated onto their 1st line DMT was 17%. In Q4 2018, it was 16%. A similar lack of significant change was seen in the US, with 13% of patients in our reported sample initiating onto their 1st line DMT in Q4 2015 compared to 14% in Q4 2018. In these same segments however, the addition of the high-efficacy options gave rise to a greater number of DMTs being used to treat patients, further suggesting neurologist willingness and comfort to use these HE DMTs alongside more traditional platform options for their new-to-treatment patients.
When looking at neurologists’ perceived disease severity of patients receiving higher efficacy DMTs (both mAbs and HE orals) in the EU5, there has been no significant change in the proportion of reported patients considered “mild” (40% Q4 2015 vs. 38% in Q4 2018). Along a similar vein, 7% of patients receiving HE DMTs did not experience any relapses in the most recent 12-month period in Q4 2015, vs 10% in Q4 2018, again highlighting no significant changes. Whilst comfort with the “treating earlier” mentality appears to be growing amongst the neurologist community, as per guidelines, they appear to be reserving these high-efficacy DMTs for their patients with more active disease. Rather than widespread use in new-to-treatment patients, neurologists have grown in confidence in using HE therapies specifically in the more active disease cohort of this patient segment. This has allowed the displacement of the more traditional platform therapies to treat active 1st line patients, instead providing MS patients with a better DMT “match’ to their disease profile.
On the flip side, there remains a cohort of reported 1st line RRMS patients in our sample who are considered to have higher clinical disease activity, but are being prescribed milder, more traditional 1st line DMTs. For example, when focusing specifically on patients new to DMT therapy with two or more relapses within the prior 12 months and 1 or more Gd lesion(s), 38% of this patient cohort in the EU5 in Q4 2018 were being treated with a platform therapy (oral or injectable). In the US, 59% of the equivalent patient cohort were receiving a platform therapy. Coming back full circle, it is clear a divide remains in the neurologist community regarding how best to treat new-to-therapy RRMS patients.
With one school of thought advocating the use of high-efficacy DMTs earlier in the MS treatment pathway for disease control benefits (including the longer term slowing of disability accumulation), there is an equally valid opposing caution to using such options “too early”, as well as risking potentially serious side effects. Whilst both treatment paradigms are evident in our data, there is a growing acceptance in the neurologist community that such therapies have a true place in patients new to disease modifying treatment. The points raised in this article highlight the importance of pharma companies acknowledging both sides of the coin in order to appropriately adapt to the needs of MS physician and patient alike.
Drug treatment patterns were investigated using EU5 and US data from the Ipsos Global Multiple Sclerosis Therapy Monitors, which are proprietary syndicated patient record databases. Specifically, physicians reported on their disease-modifying drug-treated patients seen in consultation during the study period. Physicians who participated in the Therapy Monitors were required to treat a minimum number of MS patients in a typical month and be the treatment decision maker for these patients. Dates and sample sizes are given below, and all research was conducted online. All results cited were tested for significance using Pearson’s chi-squared test; all results were significant at a threshold level of p<0.05. High-efficacy treatment options considered include Gilenya, Mavenclad, Tysabri, Lemtrada, Ocrevus; monoclonal antibodies considered include Tysabri, Lemtrada and Ocrevus specifically. Data are © Ipsos 2019, all rights reserved.
Simone Gabriele is Associate Director and Elizabeth Baynton is Associate Director – Ipsos Autoimmune Therapy Monitors.
1: www.brainwork.md. 2019. MS treatment strategy: Hitting hard and early, or minimizing risks through stepwise escalation? – www.brainwork.md. [ONLINE] Available at: https://www.brainwork.md/ms-treatment-strategy-hitting-hard-and-early-or-minimising-risks-through-stepwise-escalation/. [Accessed 28th March 2019]
2: Cerqueira, J., et al. 2019. Time matters in multiple sclerosis: can early treatment and long-term follow-up ensure everyone benefits from the latest advances in multiple sclerosis? Journal of Neurology, Neurosurgery & Psychiatry, [Online]. 89-8, 844-850. Available at: https://jnnp.bmj.com/content/89/8/844 [Accessed 28 March 2019]
3: Ipsos MS Therapy Monitor (269/321 sampled MS specialists reporting on a predefined quota of MS patients across the EU5 in Q4 2015/Q4 2018). Full methodological details available on request.
4. Ipsos MS Therapy Monitor (111/107 sampled MS specialists reporting on a predefined quota of MS patients in US in Q4 2015/Q4 2018). Full methodological details available on request.