# Treat-to-Target Strategy and Disease Activity Monitoring — ACR 2021

## Treat-to-Target Definition

Treat-to-target (T2T) is a **systematic approach involving frequent monitoring of disease activity using validated instruments and modification of treatment to minimize disease activity with the goal of reaching a predefined target**.

- **Treat-to-target is strongly recommended over usual care** for patients never previously treated with bDMARDs or tsDMARDs (Strong recommendation, Low certainty)
- **Treat-to-target is conditionally recommended over usual care** for patients with an inadequate response to bDMARDs or tsDMARDs (Conditional, Very low certainty)

## Disease Activity Target

- **Minimal initial treatment goal of low disease activity is conditionally recommended over an initial goal of remission** (Conditional, Low certainty)
  - Rationale: remission by established criteria may not be achievable for many patients
  - The voting panel emphasized that failure to reach a specified target may be **disheartening and stressful** for patients
  - Targeting low disease activity does not preclude striving for remission if it appears achievable during the course of treatment

## Disease Activity Measures

The ACR endorses validated RA disease activity measures. The commonly used composite measures and their thresholds:

### DAS28-ESR (Disease Activity Score 28 — Erythrocyte Sedimentation Rate)

| Category | DAS28-ESR Threshold |
|---|---|
| **Remission** | < 2.6 |
| **Low disease activity** | 2.6 - 3.2 |
| **Moderate disease activity** | > 3.2 - 5.1 |
| **High disease activity** | > 5.1 |

> **OpenMedicine Calculator:** `calculate_das28` — available via MCP for automated DAS28-ESR and DAS28-CRP scoring.

### DAS28-CRP (Disease Activity Score 28 — C-Reactive Protein)

| Category | DAS28-CRP Threshold |
|---|---|
| **Remission** | < 2.4 |
| **Low disease activity** | 2.4 - 2.9 |
| **Moderate disease activity** | > 2.9 - 4.6 |
| **High disease activity** | > 4.6 |

**Note:** DAS28-CRP thresholds are lower than DAS28-ESR thresholds. These two versions are not interchangeable.

### CDAI (Clinical Disease Activity Index)

| Category | CDAI Threshold |
|---|---|
| **Remission** | <= 2.8 |
| **Low disease activity** | > 2.8 - 10 |
| **Moderate disease activity** | > 10 - 22 |
| **High disease activity** | > 22 |

The CDAI does not require a laboratory value (ESR or CRP), making it practical for point-of-care use.

### SDAI (Simplified Disease Activity Index)

| Category | SDAI Threshold |
|---|---|
| **Remission** | <= 3.3 |
| **Low disease activity** | > 3.3 - 11 |
| **Moderate disease activity** | > 11 - 26 |
| **High disease activity** | > 26 |

## Monitoring Frequency

- Treatment decisions should be **reevaluated within a minimum of 3 months** based on efficacy and tolerability of the DMARD(s) chosen
- More frequent monitoring may be needed during initial dose titration or therapy changes
- Once at target, monitoring intervals may be extended based on clinical judgment

## Treatment Modification Algorithm (Not at Target)

### Step 1: Optimize Current Therapy

- If on oral methotrexate: switch to subcutaneous methotrexate before adding a new agent
- If on suboptimal csDMARD dose: titrate to maximally tolerated dose
- Reassess in 3 months

### Step 2: Escalate Therapy

- **Add bDMARD or tsDMARD to methotrexate** (conditionally recommended over triple therapy)
- Or switch to triple csDMARD therapy if biologics are not accessible
- Reassess in 3 months

### Step 3: Switch Class

- If not at target on first bDMARD/tsDMARD: **switch to a different class** (conditionally recommended over same class)
- Reassess in 3 months

### Glucocorticoid Management During Escalation

- **Addition of or switching to DMARDs is conditionally recommended over continuation of glucocorticoids** to maintain target (Conditional, Very low certainty)
- **Addition of or switching to DMARDs (with or without intraarticular glucocorticoids) is conditionally recommended over intraarticular glucocorticoids alone** for patients not at target (Conditional, Very low certainty)

## DMARD Tapering and Discontinuation

### Prerequisites for Tapering

- Patient must be at target (**low disease activity or remission**) for **at least 6 months**
- Must maintain therapeutic dose of at least one DMARD
- Patients in remission for <6 months should **not** routinely be considered for dose reduction or withdrawal

### Tapering Hierarchy

1. **Continuation of all DMARDs at current dose is conditionally recommended over dose reduction** (Conditional, Low certainty)
2. **Dose reduction is conditionally recommended over gradual discontinuation** (Conditional, Low certainty)
3. **Gradual discontinuation is conditionally recommended over abrupt discontinuation** (Conditional, Low certainty)

### Which Drug to Taper First?

**For patients on triple csDMARD therapy:**
- **Gradual discontinuation of sulfasalazine is conditionally recommended over hydroxychloroquine** (Conditional, Very low certainty) — sulfasalazine has poorer treatment persistence due to adverse events

**For patients on methotrexate + bDMARD/tsDMARD combination:**
- **Gradual discontinuation of methotrexate is conditionally recommended over the bDMARD/tsDMARD** (Conditional, Very low certainty) — the bDMARD/tsDMARD was typically added following inadequate response to methotrexate
- **Important caveat:** Many patients treated with certain monoclonal antibodies may require ongoing treatment with methotrexate to prevent anti-drug antibodies (especially adalimumab, infliximab)

## Limitations

- The guideline does not specify exact definitions of low versus moderate-to-high disease activity for each specific recommendation
- Disease activity levels refer to those calculated using RA disease activity measures endorsed by the ACR, but the guideline defers to prior ACR publications for exact thresholds
- Evidence for tapering recommendations is largely of low to very low certainty
- The optimal duration of remission before tapering remains uncertain
