# Flare Management in Gout — ACR 2020

## Acute Gout Flare Treatment

### First-Line Therapies

Colchicine, NSAIDs, or glucocorticoids (oral, intraarticular, or intramuscular) are **strongly recommended** as first-line therapy for gout flares over IL-1 inhibitors or ACTH (Strong, High).

The choice among these agents should be made through **shared decision-making** based on patient comorbidities, prior treatment response, and concurrent medications.

### Colchicine for Acute Flare

**Low-dose colchicine** is strongly recommended over high-dose colchicine for gout flares (Strong, High).

| Parameter | Recommendation |
|---|---|
| **Regimen** | 1.2 mg orally immediately, followed by 0.6 mg orally 1 hour later |
| **Maximum first-day dose** | 1.8 mg total |
| **Ongoing therapy** | Continue anti-inflammatory therapy until flare resolves |
| **Timing** | Most effective when started within 12 hours of flare onset |

- The low-dose regimen (from the AGREE trial) is as effective as high-dose colchicine with significantly fewer gastrointestinal adverse effects (diarrhea, nausea, vomiting).

### NSAIDs for Acute Flare

NSAIDs are strongly recommended as a first-line option (Strong, High).

- Three NSAIDs are FDA-approved for treatment of acute gout: **indomethacin, naproxen, and sulindac**.
- NSAIDs should be used at full anti-inflammatory doses.
- Contraindications include active peptic ulcer disease, CKD, and concurrent anticoagulant use.

### Glucocorticoids for Acute Flare

Glucocorticoids (oral, intraarticular, or intramuscular) are strongly recommended as a first-line option (Strong, High).

| Route | Details |
|---|---|
| **Oral** | Prednisone or prednisolone; initiate at an appropriate dose, taper, and discontinue over several days |
| **Intraarticular** | Preferred for monoarticular flares; injection directly into the affected joint |
| **Intramuscular** | Option for patients unable to take oral medications or with polyarticular flares |

### Flare Treatment Decision Algorithm

```
Acute gout flare confirmed
  --> Can the patient take oral medications?
      --> YES
          --> Any contraindication to colchicine?
              --> NO --> Low-dose colchicine (1.2 mg then 0.6 mg in 1 hour)
              --> YES
                  --> Any contraindication to NSAIDs?
                      --> NO --> Full-dose NSAID (indomethacin, naproxen, or sulindac)
                      --> YES --> Oral glucocorticoid (prednisone/prednisolone)
          --> Monoarticular flare accessible for injection?
              --> Consider intraarticular glucocorticoid
      --> NO (cannot take oral medications)
          --> Parenteral glucocorticoid (IM or IV) is strongly recommended
              over IL-1 inhibitor or ACTH (Strong, High)
```

### Second-Line: IL-1 Inhibitors

An IL-1 inhibitor is **conditionally recommended** for patients with gout flares for whom colchicine, NSAIDs, and glucocorticoids are **ineffective, poorly tolerated, or contraindicated** (Conditional, Moderate).

- IL-1 inhibitors include anakinra and canakinumab.
- These are not first-line agents and should be reserved for refractory situations.

### Adjuvant Therapy

**Topical ice** applied to the affected joint is conditionally recommended as an adjuvant measure during gout flares (Conditional, Low).

## Anti-Inflammatory Prophylaxis During ULT Initiation

### Indication

When initiating ULT, concomitant anti-inflammatory prophylaxis therapy is **strongly recommended** over no prophylaxis (Strong, Moderate). ULT initiation frequently triggers gout flares due to mobilization of urate crystals during serum urate lowering.

### Prophylaxis Agents

| Agent | Dose | Notes |
|---|---|---|
| **Colchicine** | 0.6 mg once or twice daily orally | Preferred prophylaxis agent; low-dose reduces GI adverse effects |
| **NSAIDs** | Low-dose (e.g., naproxen 250 mg twice daily) | Alternative if colchicine not tolerated |
| **Prednisone/prednisolone** | <= 10 mg/day orally | For patients who cannot take colchicine or NSAIDs |

### Duration of Prophylaxis

Continuing prophylaxis for **3-6 months** is **strongly recommended** rather than < 3 months (Strong, Moderate).

```
ULT initiated
  --> Start anti-inflammatory prophylaxis concurrently
      --> Preferred: colchicine 0.6 mg once or twice daily
      --> Alternative: low-dose NSAID or prednisone <= 10 mg/day
  --> Continue for minimum 3-6 months
  --> At 3-6 months:
      --> Patient still experiencing flares?
          --> YES --> Continue prophylaxis with ongoing evaluation
          --> NO --> May consider discontinuation
```

### Prophylaxis Principles

- Prophylaxis should be started **at the same time as ULT**, not delayed.
- The duration of >= 3-6 months reflects the typical time required to deplete tissue urate stores; patients with large tophaceous burden may require longer prophylaxis.
- Ongoing evaluation is recommended; if flares continue beyond 6 months, prophylaxis should be continued.

## Limitations

- The guideline does not specify exact glucocorticoid doses or taper schedules for acute flares, leaving this to clinical judgment.
- Optimal NSAID choice and dosing for acute flares are not differentiated within the guideline; all three FDA-approved agents are considered equivalent.
- The evidence for topical ice as adjuvant therapy is based on low-certainty evidence.
- IL-1 inhibitor recommendations are based on moderate-certainty evidence, and access and cost may limit their use in practice.
- Prophylaxis duration beyond 6 months has not been rigorously studied in randomized trials.
