Tocilizumab

The current standard of care in RA is to make the diagnosis early, start the patient on MTX, escalate the dose according to clinical response and drug tolerability, and maybe combine with other conventional DMARDs if necessary. Only if clinical remission (CR) or low disease activity (LDA) cannot be achieved in a “reasonable time frame” (3-6 months?) would a targeted therapy be introduced.

Ultimately, regardless of what you start with, or what therapeutic switches or adjustments are made, as long as you stick with the tight-control-close-monitoring mantra of the day, almost everyone should achieve the target of CR or LDA at the end of 2 years of therapy.

So, are there any advantages to bringing on the costly biologics earlier for most patients? This and other trials (eg AVERT for Abatacept, BeSt for Infliximab, OPTIMA for Adalimumab) suggest so:
1) Tocilizumab monotherapy is better than MTX alone, and as good as combination with MTX in achieving remission. So if you tolerate MTX poorly, or are worried about MTX toxicity, Tocilizumab alone is your best choice;
2) Initial Tocilizumab use was associated with lesser structural damage (joint erosions), though the difference may not be clinically significant, and extrapolation of linear progression to eventual disability may be erroneous. But why risk more damage?
3) Remission is achievable (earlier?) with fewer or no need for drug switches/adjustments;
4) Drug-free remission (DFR) after 6 months of CR is more likely if you started off with Tocilizumab rather than with MTX.
Not mentioned in this review, but demonstrated in the other biologic trials listed afore, are patient-centric measures like earlier functional restoration, less time off work, better quality of life, and even therapeutic preference.

So, yes, if finances and healthcare resources are not particularly constrained, a good case can be made for initiating the targeted therapies at the get-go. Boils down again to my air travel analogy: the class you choose/pay defines your travel experience, not your destination.

One criticism often levelled at the “Fast & Furious” camp (of which I’m an early adopter and fervent advocate of) is the unnecessary costly over-treatment of the majority (80% who would remit easily) just to salvage the few (20% rapid progressors).
The typical smug retort is: if you have the disease and you have means, how would you choose?

This study also gives a hint that challenges the conventional wisdom. One atypical finding is the high proportion of patients achieving sustained remission and even drug-free remission, even amongst those on initial MTX alone. This may be due to the low bar for inclusion: DAS28>2.6 (when remission was defined as DAS28 <2.6), and less than 1 year of disease; resulting in an over-representation by those with milder disease. But this is precisely the “early/mild disease, good prognosis” group that one considers most likely to remit with simple measures (eg MTX, with perhaps some low dose, short duration steroids). Yet, statistically significant differences were demonstrated in terms of sustained remission rates, erosions, and drug-free remission rates.

Possibly even, such stark differences were achieved not “in spite of”, but “because of” initiating Tocilizumab in those with “early and mild” disease. This would make sense in the current concept that there exists a small window of opportunity (3-6 months) from the onset of disease wherein the disease is less entrenched and more amenable to being eradicated by sufficiently aggressive immunosuppressive therapy.