# Glucocorticoid Recommendations and Special Populations — ACR 2021

## Glucocorticoid Recommendations

### General Principles

- Treatment with glucocorticoids should be limited to the **lowest effective dose for the shortest duration possible**
- The toxicity associated with glucocorticoids was judged to **outweigh potential benefits**
- There is increasing evidence of the negative impact of glucocorticoids on long-term patient outcomes, including risk for infection, osteoporosis, and cardiovascular disease

### Short-Term Glucocorticoids (<3 Months)

- **Initiating a csDMARD WITHOUT short-term (<3 months) glucocorticoids is conditionally recommended over WITH short-term glucocorticoids** (Conditional, Very low certainty)
- The panel acknowledged that short-term glucocorticoids are frequently **necessary to alleviate symptoms prior to onset of action of DMARDs**
- When used, glucocorticoids should serve as a **bridge** while waiting for DMARD efficacy (typically 4-12 weeks)

### Longer-Term Glucocorticoids (>=3 Months)

- **Initiating a csDMARD WITHOUT longer-term (>=3 months) glucocorticoids is strongly recommended over WITH longer-term glucocorticoids** (Strong recommendation, Moderate certainty)
- This is one of only 7 strong recommendations in the guideline

### Glucocorticoid-Dependent Patients

- **Addition of or switching to DMARDs is conditionally recommended over continuation of glucocorticoids** to maintain disease activity target (Conditional, Very low certainty)
- **Optimizing DMARDs is conditionally recommended over initiation or dose escalation of glucocorticoids** for patients not at target (Conditional, Very low certainty)

### Intraarticular Glucocorticoids

- **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)
- Intraarticular injections may be useful as **adjunctive therapy** for individual joint flares but should not replace systemic DMARD optimization

### Glucocorticoid Decision Algorithm

1. **DMARD-naive patient with moderate-to-high disease activity:**
   - Start methotrexate WITHOUT glucocorticoids (preferred)
   - If symptoms require bridging: use the lowest effective dose for <3 months
   - Plan explicit glucocorticoid taper and discontinuation schedule
2. **Patient currently on glucocorticoids:**
   - Optimize DMARD therapy to permit glucocorticoid tapering
   - Target glucocorticoid discontinuation rather than maintenance
3. **Patient not at target:**
   - Escalate DMARDs rather than increasing glucocorticoid dose
   - Consider intraarticular glucocorticoids only as adjunct, not sole therapy

## Special Populations

### Hepatitis B Infection

**Patients initiating rituximab who are hepatitis B core antibody positive (HBcAb+):**
- **Prophylactic antiviral therapy is strongly recommended over monitoring alone** (Strong recommendation, Very low certainty)

**Patients initiating ANY bDMARD/tsDMARD who are HBcAb+ AND HBsAg+:**
- **Prophylactic antiviral therapy is strongly recommended over monitoring alone** (Strong recommendation, Very low certainty)

**Patients initiating non-rituximab bDMARD/tsDMARD who are HBcAb+ but HBsAg-:**
- **Frequent monitoring alone is conditionally recommended over prophylactic antiviral therapy** (Conditional, Very low certainty)

### Nontuberculous Mycobacterial (NTM) Lung Disease

- **Use the lowest possible glucocorticoid dose (discontinuation if possible) is conditionally recommended** over continuation without modification (Conditional, Very low certainty)
- Requires **close co-management with infectious disease or pulmonary specialist**
- **Addition of csDMARDs is conditionally recommended over bDMARD/tsDMARD** for moderate-to-high disease activity despite csDMARD monotherapy (Conditional, Very low certainty)
- **Abatacept is conditionally recommended over other bDMARDs/tsDMARDs** when escalation beyond csDMARDs is needed (Conditional, Very low certainty)
- **TNF inhibitors should be avoided** — they are associated with increased rates of mycobacterial infections

### Previous Serious Infection (Within 12 Months)

- **Addition of csDMARDs is conditionally recommended over addition of bDMARD/tsDMARD** for patients with moderate-to-high disease activity despite csDMARD monotherapy (Conditional, Very low certainty)
- **Optimizing DMARDs is conditionally recommended over initiation or dose escalation of glucocorticoids** (Conditional, Very low certainty)
- If bDMARD/tsDMARD is needed, selection should weigh infection risk profile of specific agents

### Lymphoproliferative Disorder History

- **Rituximab is conditionally recommended over other DMARDs** for patients with a history of lymphoproliferative disorder for which rituximab is an approved therapy, with moderate-to-high disease activity (Conditional, Very low certainty)

### Heart Failure (NYHA Class III-IV)

- **Non-TNF inhibitor bDMARD/tsDMARD is conditionally recommended over TNF inhibitor** for patients who have an inadequate response to csDMARDs (Conditional, Very low certainty)
- **Switch to non-TNF inhibitor bDMARD/tsDMARD is conditionally recommended** for patients who develop heart failure on a TNF inhibitor (Conditional, Very low certainty)

## Related ACR Guidelines for Special Populations

The 2021 ACR RA Treatment Guideline explicitly defers to companion ACR guidelines for the following topics:

### Vaccination (ACR 2022 Vaccination Guideline; DOI: 10.1002/acr.25045)

Key cross-referenced recommendations:
- **All age-appropriate vaccinations should be administered** per standard immunization schedules before initiating immunosuppressive therapy when possible
- **Live-attenuated vaccines should be deferred** for patients on immunosuppressive medications; hold the immunosuppressive medication for an appropriate period before and 4 weeks after vaccination
- **Methotrexate should be held for 2 weeks after influenza vaccination** if disease activity allows
- **Non-influenza vaccines should be given at least 6 months after the last rituximab dose** when possible
- Patients on rituximab should still receive seasonal influenza vaccine regardless of timing

### Perioperative Management (ACR/AAHKS 2022 Perioperative Guideline; DOI: 10.1002/acr.24893)

Key cross-referenced recommendations for elective total hip or total knee arthroplasty:
- **Continue methotrexate, leflunomide, hydroxychloroquine, sulfasalazine** through surgery (Conditional)
- **Withhold all biologic DMARDs** prior to surgery; plan surgery after the next scheduled dose is due and restart once wound healing is satisfactory (typically 14 days postoperatively)
- **Withhold JAK inhibitors (tofacitinib, baricitinib, upadacitinib) for at least 3 days** prior to surgery (Conditional) — JAK inhibitors have rapid onset/offset, so a shorter withholding period is sufficient
- Perioperative glucocorticoid management: administer the usual daily dose rather than supraphysiologic stress-dose steroids

### Reproductive Health and Pregnancy (ACR 2020 Reproductive Health Guideline; DOI: 10.1002/acr.24130)

Key cross-referenced recommendations:
- **Methotrexate must be discontinued at least 3 months before conception** in both men and women (Strong recommendation)
- **Leflunomide must be discontinued with cholestyramine washout** (8 g three times daily for 11 days) before conception or as soon as pregnancy is confirmed
- **Hydroxychloroquine and sulfasalazine are compatible with pregnancy** and should be continued
- **Certolizumab pegol is strongly recommended for continuation** prior to and during pregnancy — it lacks an Fc portion and has minimal placental transfer
- **Other TNF inhibitors (etanercept, adalimumab, infliximab, golimumab)** are conditionally recommended to continue prior to and during pregnancy; they do not cross the placenta significantly during the first trimester
- **JAK inhibitors, rituximab, abatacept, and tocilizumab** should be discontinued before conception due to insufficient safety data

## Limitations

- The 2021 ACR RA Treatment Guideline does not itself contain detailed vaccination, perioperative, or pregnancy recommendations — it defers to the companion ACR guidelines cited above
- Glucocorticoid dose thresholds (e.g., prednisone <=7.5 mg/day) are not explicitly defined in this guideline
- Special population recommendations are based almost entirely on very low certainty evidence
- The guideline does not address hepatitis C (due to availability of curative antiviral therapy), solid malignancies, or checkpoint inhibitor therapy (insufficient evidence)
