Сергей Пузанов – Multiple Sclerosis. Everything you need to know (страница 15)
Here is a curious detail: during the trials for the very first interferon, the EDSS score wasn't even the primary endpoint; they only tracked the number of relapses. When the investigators finally pulled up the data charts for the EDSS scale, they got hit with a freezing shower: the disability progression curves for the placebo group and the Betaseron group practically merged. Mathematically, there was zero significant difference in how their EDSS scores shifted. Despite this, the interferon beta-1b rammed through regulatory approval anyway. However, subsequent DMTs were forced to use disability progression as an endpoint, and the flexibility of interpreting EDSS scores turned out to be incredibly convenient.
The structural vulnerability of the EDSS is that the calculator has been stripped down to a single, flattened final score. Instead of evaluating the patient's status across several distinct functional tracks (cerebellar, visual, bowel/bladder, cognitive, and so on), everything was boiled down to a flat text description of the output. Up to 1.5 points maps to minimal impairment; 2.0 to 3.5 logs moderate issues; and starting right at 4.0, everything hinges strictly on walking distance. After 6.0, the patient requires an assistive device to move; after 7.0, they are restricted to a wheelchair; and past 8.0, they are bedridden and lose significant use of their hands. Look closely at this imbalance: from 0 to 3.5, the patient is more or less functional, but the transition from 4.0 to 7.5 is a slippery slide from minor limitations to total helplessness. The non-linear structure of the EDSS is a prime variable for cooking efficacy numbers: hand-picking the right patients for a trial allows researchers to heavily manipulate the final data.
Some medical registries don't even bother separating scores below 3.5—these impairments are dumped into a single basket and labeled as "mild or moderate". This framework grants investigators massive creative freedom when logging disability shifts, which can artificially inflate the proven efficacy of drugs during trials with compromised blinding. If researchers can guess who is getting the drug and who is stuck on a placebo, the fuzzy line between "mild" and "moderate" impairments can manufacture a wall of statistical noise spanning up to two full points. However, past the 4.0 mark, things aren't any cleaner: the scale shifts its focus exclusively to walking distance, completely blinding itself to other issues. If at a 4.0 mark a patient can trudge 500 meters without resting, the scale doesn't give a damn about how well their hands, eyes, cognition, or bladder are functioning.
When a score is anchored entirely to walking, any decline that doesn't involve the legs can be legally ignored. Vision dropped? "Doesn't move the EDSS". Memory loss, speech glitches, or executive decline? "EDSS remains stable". A tremor takes over the hand, making it impossible to hold a fork? "The scale failed to register a shift". Crushing fatigue, an inability to get out of bed, anxiety, apathy, or depression? "Disability metric is completely stable". This obsessive fixation on walking is the primary flaw of the EDSS. When a pharmaceutical giant boasts that "patients maintained a stable score throughout the therapy," in reality, it frequently means nothing more than the fact that they could still walk. What is happening to the brain tissue remains a mystery; fine motor skills are ignored; bowel/bladder issues and cognitive decline are written off. A patient can lose the ability to tie their shoes due to tremors, but as long as their legs clock the mandatory distance, clinical reports will cheerfully log "moderate" impairment.
Yet, the EDSS manufactures a convincing illusion of rigorous science for patients. EDSS 1.5? Great, nothing to worry about, the impairment is mild—it doesn't matter that the patient can no longer read books and has spent the last year working at half capacity. EDSS 2.5? Zero disability progression, it doesn't matter that the patient breaks down crying every evening because they can no longer track their own thoughts. EDSS 3.5? Still no reason to panic, the impairment is moderate—it doesn't matter that the patient has to run to the bathroom every thirty minutes. A hard number for the degree of disability exists—and on that number, you can build a clean chart, a scientific publication, and an aggressive marketing strategy without asking a single uncomfortable question about the patient's actual status. The main thing is to build an illusion of control and keep the patient from realizing that the number doesn't map reality.
In the end, a scale that was engineered to measure neurological deficits turned into a convenient facade used to mask degradation. The EDSS is completely defenseless against statistical juggling. If you need to prove a drug works, you screen for mild patients, deploy the baseline therapy, and watch their legs. If the data fails, you can always claim that "the EDSS missed the improvement because the scale lacks sensitivity". It’s a universal tool—perfect for pushing drugs and equally perfect for dodging uncomfortable data. Patients are hemorrhaging physical power and bodily functions, but on the EDSS chart, "no disability progression is observed".
Are there alternatives to the EDSS? Yes, plenty of them: MSFC (Multiple Sclerosis Functional Composite), PROMs (Patient-Reported Outcome Measures), Floodlight, and others. Among the old guard, almost simultaneously with the expansion of Kurtzke's scale, the Scripps Research Institute engineered its own tracking matrix—the Scripps Neurologic Rating Scale (SNRS). The SNRS measures far more than the ability to walk: it audits muscle strength, coordination, balance, gait, sensory mapping, speech, vision, reflexes, cerebellar functions, eye movement tracking, general neurological integration, and bowel/bladder functions. This instrument is also far from flawless, but in terms of sensitivity and completeness, it sits incomparably closer to the actual clinical profile. In plain terms, the phrase "no disability progression by the SNRS scale" would carry far more weight than an identical claim regarding the EDSS.
Yet, for clinical trials and pharmaceutical reporting, the industry chose the EDSS. Why? Because Kurtzke's scale carried the institutional weight of being used in the US military, and because the extreme sensitivity of the SNRS terrified drug manufacturers. Why deploy an instrument that logs every minor glitch when the EDSS allows you to turn a blind eye to them? As a result, the EDSS became the gold standard of the industry, even though the SNRS could have delivered a far more honest picture. The EDSS is streamlined for rapid auditing—thanks to its instant score generation—but it completely ignores an array of symptoms that dictate a patient's quality of life. Take me, for example: during my worst stretches, I couldn't close my eyes while washing my hair in the shower—I would instantly lose balance and crash to the floor. Yet, this total failure of equilibrium didn't shift my EDSS score by a single fraction of a point.
Chapter 3. The Interferon War
The Birth of DMTs: The Wheelchair Assault and Big Pharma’s Lottery
To truly understand how the era of interferons kicked off, you have to flash back to the early 1990s. Picture a world in the middle of a massive tech boom. Humanity is advancing in leaps and bounds. Your neighbor just bought a car equipped with parking sensors, a navigation system, and an automatic transmission. Televisions are in every home, broadcasting news about biotechnology, genetic engineering, and stem cells. Bill Gates has already built Microsoft and is predicting an explosion of something called the Internet—whatever that is. More and more people are carrying mobile phones, and the devices are getting smaller and sleeker by the day.
Back in 1980, the WHO announced that mass vaccination had completely wiped smallpox off the face of the Earth. Stomach ulcers can now be cured in a couple of weeks with a simple course of antibiotics, because it turns out a bacterium called