Mind the Gap

Dear Friend,

I once lived on Baker Street in Central London; my daily commute to St. Thomas’ Hospital was on the London Tube trains. The train's iconic map was etched in my mind: take the Jubilee silver line, hop on over to Westminster Bridge, and then a short walk to Tommy’s. Colored lines crisscrossing a whole city. Neat right angles. Nodes and interchanges. Every junction a decision; change here, stay on, two stops and you're at your destination. It is a miracle of design: point A to point B, in the fewest possible moves.

That map is a promise. Get on, and we'll get you there.

It's the same promise a rheumatologist and your doctor make. Here is the route. Take methotrexate for your rheumatoid arthritis, then a biologic, then a switch if the first one doesn't get you pain-free. Escalate here. Change lines there. Get the inflammation under control, and you hopefully arrive. The routes are real. The medicines are real. The advances of the last two decades are extraordinary, and nobody should be casual about that.

But the map is not the terrain.

The map doesn't show the signal failure at Baker Street. The train held in the tunnel with no explanation. The lift, the elevator, out again at the station. Time is ticking, and you're late for work. The journey happens in a body, your body, in unpredictable weather, in lost time you can't get back.

There's a warning plastered all over the London Underground: Mind the Gap. As a train pulls in, space can open between the door and the platform edge. Small, easy to miss. And you can fall right into it.

So, it goes with disease. The trial says the joint counts came down. The graph says response achieved. And you are still on the platform, tired in a way no endpoint records, planning your week around a fatigue that doesn't appear in any chart, wondering why treated and better turned out to be two different destinations. The delays. The frustration. The pain.

That distance, between the route we drew and the journey people are actually taking, is the gap. This newsletter stands at that edge and looks down.

Mind the gap.

What's the Gap in the Data?

To see the gap, you have to know how we measure a win.

In rheumatoid arthritis, we use the ACR score. ACR stands for the American College of Rheumatology, the body that sets the yardstick. ACR20 means a patient improved by 20%. ACR50, by 50%. ACR70, by 70%: joints, pain, and function all substantially better. ACR70 is the big one, the marker of a major response, and the highest bar most drug trials report. But notice what the number really means. It measures improvement, not arrival. ACR70 is not the same as well. It is 70% of the way from where you started.

Medicine works this way almost everywhere. We pick a number and call it the target. Blood pressure under 130. Cholesterol (LDL) under 100. BMI under 25. Blood sugar (A1c) under 6. Hit the number and the chart says "controlled." It is a useful habit. It is also a quiet substitution: the target stands in for the person. You can hit every number and still not feel well, and the graph will not know the difference.

As a doctor, I read these graphs for a living. The bars climb. The response is "achieved." But I have learned to look at what sits above the bar, the empty space the drug never reached.

In the pivotal trial for Humira (adalimumab), one of the first biologics to change how we treat RA, roughly one in four patients reached ACR70, the trial's marker of a major clinical response, at six months. Weinblatt and colleagues published the ARMADA trial in Arthritis & Rheumatism in 2003. It is real data, from a real drug that has changed real lives.

On Humira, three out of four patients did not reach ACR70. Let’s sit with the number for a moment. What is hiding in that empty space above the bars?

It means three out of four patients, on that same drug, in that same trial, did not reach the mark for a major response. Some improved a little. Some improved a lot, just not enough to clear that particular bar. The chart cannot tell you which. A bar graph has only two dimensions. You have many more.

I have used Humira thousands of times. It is a good biologic, and it has changed many lives. And still, some patients never respond, and some stop responding altogether. Why? How does someone fall into the gap? Which patient will respond, and which will not? I cannot always tell. There is no crystal ball.

So the important question is this: what holds the other three in four back? Part of the answer is in how the bar was built. ACR70 measures joints: tender counts, swollen counts. It was never built to measure the whole architecture of a life. It cannot see sleep. It cannot see the gut. It cannot see whether someone recognizes themselves in the mirror again. The graph does not capture the whole patient.

Medicated is not the same as well.

A New Biologic on the Launch Pad

The gap is not a relic of older drugs. It holds even in a medicine that is brand new.

I looked at a preprint: a phase 3 trial of a new oral drug for psoriatic arthritis, a TYK2 inhibitor, published in Arthritis & Rheumatology in July 2026. Different disease. Different decade. Different mechanism: an oral pill, not an injected antibody.

And a full year in trial, the same ceiling. Roughly one in four patients reached ACR70. The same one in four as Humira, two decades earlier.

The route got newer. The destination did not move.

This is not about one molecule failing anyone. And even the newest medicine, tested to the highest modern standard, still shows the same gap. The gap does not close because the science gets newer. It closes, if it closes at all, when someone asks the second question this newsletter keeps asking: not just did you respond, but are you well?

Your Burning Questions

What keeps you up at 3 AM?

This story isn't about new biologics or the next cool technology. It is about you. Every real inquiry starts with one question, the one you keep researching, the one you Google at 3 AM. That is how science begins. So I am turning it toward you. Where are you not seen? What is YOUR gap? Say it, write it, share it. A gap can widen. It doesn't have to.

Are you on a biologic? That is a yes-or-no question. It has a chart behind it: which drug, what dose, how many weeks, and somewhere in a spreadsheet, whether you crossed the ACR70 line or fell short.

Are you well? That is not a yes-or-no question, and it has no chart. It asks about sleep that restores you. A gut that behaves. Energy left at the end of the day for the people you love, not just the job in front of you. Whether the person in the mirror still feels like you.

You can answer yes to the first and still be searching for an answer to the second. That gap, between being medicated and being well, is not a failure of the drug or of the patient. It is what happens when we let a two-dimensional graph stand in for a life that was never two-dimensional. I have read these charts for years, and again and again I encounter patients who are not the same as their numbers.

This is the gap I want this newsletter to mind. And it is not just rheumatology. Diabetes, thyroid disease, heart disease, autoimmune conditions of every kind: wherever medicine picks a number and calls it the target, the same gap opens.

This is the gap I want this newsletter to mind.

Your Turn

This issue, I want to hear from you, whichever side of the exam table you sit on, and whatever condition you have.

If you live with a chronic illness: are you well? Not "is your bloodwork better." Are you better, sleeping, eating, showing up as yourself? Where do you feel the gap in your healing, in the clinic, at home, or somewhere in between?

If you are a physician, nurse, or PA: where do you see this gap in your own patients, in any condition? What does the chart never tell you?