Safe NSAIDs and DMARDs for Breastfeeding Patients with Enthesitis
For a breastfeeding patient with enthesitis, ibuprofen and naproxen are the safest NSAIDs, while hydroxychloroquine, sulfasalazine, TNF inhibitors (especially certolizumab), and azathioprine are safe DMARDs to continue during lactation. 1, 2, 3
NSAIDs During Breastfeeding
The 2025 EULAR guidelines confirm NSAIDs are compatible with breastfeeding, with no new safety concerns identified 1. Among NSAIDs, ibuprofen is the preferred first-line choice as it has been used extensively for postpartum pain and during lactation with established safety 2.
Naproxen is also safe despite its longer half-life compared to other NSAIDs; it's widely used after cesarean section and breastfeeding may continue normally 2.
Diclofenac appears in breast milk in small amounts but has been used extensively during lactation and is considered safe 2.
Celecoxib (a COX-2 inhibitor) exposes infants to very low relative doses via milk and is compatible with breastfeeding 2.
Ketorolac shows low levels in breast milk without demonstrable adverse effects in neonates and is compatible with breastfeeding 2.
Important Caveat
Avoid aspirin in analgesic doses during breastfeeding; only low-dose aspirin for antiplatelet action may be used if strongly indicated 2.
DMARDs During Breastfeeding
Conventional Synthetic DMARDs (csDMARDs)
Hydroxychloroquine is strongly recommended as compatible with breastfeeding 3. The 2025 EULAR data confirms very low levels in human milk 1. This is a first-line choice for enthesitis management during lactation.
Sulfasalazine (and its active metabolite mesalamine) is strongly recommended as compatible with breastfeeding 3. Multiple guidelines uniformly support its use 4. The 2025 EULAR review found very low levels in human milk 1. However, use caution in infants with glucose-6-phosphate dehydrogenase deficiency, hyperbilirubinemia, or prematurity 4.
Azathioprine/6-mercaptopurine is conditionally recommended as compatible with breastfeeding 3. Data from 102 breastfed infants showed no increased infection rate in the first 12 months of life 1. These drugs show little to no transfer into breast milk with negligible infant serum levels 5.
Biologic DMARDs (bDMARDs)
TNF inhibitors are considered compatible with breastfeeding based on the 2025 EULAR consensus 1. This represents the strongest evidence among biologics, with 245 cases of TNFi exposure during lactation showing bDMARDs are undetectable or appear in minimal amounts (<0.5 μg/mL) in breast milk 1.
Certolizumab pegol has minimal to no transplacental transfer and is particularly favorable, though this property is more relevant for pregnancy than lactation 6.
During follow-up of breastfed infants exposed to various bDMARDs, no serious infections, adverse vaccination effects, or cytopenias were reported 1.
Non-TNFi bDMARDs (tocilizumab, rituximab, abatacept, anakinra) are conditionally recommended as compatible with breastfeeding 3, with 69 cases showing undetectable or minimal amounts in breast milk 1. However, expert disagreement exists (25-31%) regarding agents without extensive breastmilk transfer data like abatacept 4.
Drugs to AVOID During Breastfeeding
Methotrexate should be avoided during breastfeeding according to most guidelines 4, 3. While 6 cases showed undetectable or very low levels in breast milk (even at ≤25 mg weekly) with no harm during 9-month follow-up 1, and the 2025 EULAR suggests it may be considered if no alternative exists 6, the consensus remains to avoid it due to potential accumulation in neonatal tissues 3.
Leflunomide is uniformly contraindicated during breastfeeding across all guidelines 4, 6, 3.
JAK inhibitors (tofacitinib, baricitinib, filgotinib, upadacitinib) should be avoided due to insufficient data 6. While limited tofacitinib data shows low breast milk concentrations (<0.1 μg/mL) without severe adverse events 1, current guidelines recommend avoidance 6.
Glucocorticoids
Prednisone <20 mg daily is compatible with breastfeeding 3. The 2025 EULAR data confirms oral prednisone/prednisolone (4.0-15.0 mg/day) appears at very low concentrations in breast milk 1.
For doses ≥20 mg daily, delay breastfeeding or discard breast milk for 4 hours following administration 3. Maximum methylprednisolone levels occur 1-2 hours after application 1.
Practical Algorithm for Enthesitis Management During Breastfeeding
- First-line: Ibuprofen or naproxen for symptomatic relief + hydroxychloroquine or sulfasalazine as DMARD
- If inadequate response: Add or switch to TNF inhibitor (all are compatible; certolizumab preferred if pregnancy is also a consideration)
- If TNF inhibitor fails: Consider another TNF inhibitor or non-TNFi biologic (tocilizumab, rituximab, abatacept)
- Adjunctive therapy: Prednisone <20 mg daily if needed for disease control
- Avoid entirely: Methotrexate, leflunomide, JAK inhibitors, aspirin in analgesic doses
This approach prioritizes maternal disease control (which directly impacts quality of life and prevents morbidity from uncontrolled inflammation) while maintaining breastfeeding safety based on the most recent 2025 EULAR evidence.