This handout is for connective-tissue-disease-associated ild (ctd-ild / ipaf). Your care team identified this based on: known ctd (ssc/ra/iim/sjögren/mctd/sle) + new dyspnea / cough / pft decline / hrct change (acr/chest 2023).
Other reasons your team may use this plan: hrct ild pattern (nsip > uip; ra-ild often uip) in a patient with autoimmune features (acr/chest 2023); progressive exertional dyspnea + dry cough with extrapulmonary autoimmune features (acr/chest 2023); newly discovered ild + positive ana/ena/rf/ccp/myositis serology (ipaf — fischer ers/ats 2015).
Take these medications exactly as prescribed. Do not stop or change a dose without talking to your provider.
| Medication | Starting dose | How | When | What it does |
|---|---|---|---|---|
| mycophenolate mofetil | 500 mg PO BID, titrate to target 1500 mg PO BID as tolerated | PO | BID | SLS II (Tashkin Lancet Respir Med 2016 PMID 27469583): MMF 24 mo ≈ oral CYC 12 mo on %FVC (no significant between-group difference p=0.24) with markedly less toxicity (leucopenia 4 vs 30; fewer deaths 5/69 vs 11/73) → MMF preferred first-line for most CTD-ILD. Teratogenic — contraindicated in pregnancy (REMS); reliable contraception required |
| cyclophosphamide | IV 500–750 mg/m2 q4 weekly (or oral ≤2 mg/kg/day per SLS I); pulse preferred for toxicity | IV | q4 weeks (induction course) | SLS I (Tashkin NEJM 2006 PMID 16790698): oral CYC vs placebo improved 12-mo FVC%-pred by +2.53% (95% CI 0.28–4.79; P<0.03). Reserve for severe/rapidly progressive disease or as combination component in anti-MDA5 RP-ILD (Tsuji 2020 PMID 31524333). Teratogenic, gonadotoxic, hemorrhagic cystitis (mesna + hydration), myelosuppression — contraindicated in pregnancy |
| rituximab | 1000 mg IV at weeks 0 and 2 (RECITAL regimen) | IV | weeks 0 and 2, repeat per B-cell/clinical course | RECITAL (Maher Lancet Respir Med 2023 PMID 36375479): rituximab NOT superior to IV CYC (24-wk FVC difference −40 mL, 95% CI −153 to 74, p=0.49) but EQUIVALENT efficacy with fewer adverse events (445 vs 646) and lower corticosteroid exposure → viable alternative to IV CYC for severe CTD-ILD requiring IV therapy. Screen HBV; infusion reactions; infection/hypogammaglobulinaemia risk |
| tocilizumab | 162 mg SC weekly | SC | weekly | focuSSced (Khanna Lancet Respir Med 2020 PMID 32866440): primary skin (mRSS) endpoint NOT met (p=0.10), but secondary FVC%-predicted favoured tocilizumab (LSM difference 4.2, 95% CI 2.0–6.4, nominal p=0.0002) → preserves lung function in early dcSSc-ILD with elevated acute-phase reactants. GI-perforation risk (caution with diverticulitis/steroids/NSAIDs); infection; LFT/lipid/neutrophil monitoring |
| nintedanib | 150 mg PO BID (100 mg BID if Child-Pugh A / poor tolerance) | PO | BID WITH FOOD | SENSCIS (Distler NEJM 2019 PMID 31112379): SSc-ILD adjusted annual FVC −52.4 vs −93.3 mL/yr (Δ 41.0 mL/yr; 95% CI 2.9–79.0; P=0.04). INBUILD (Flaherty NEJM 2019 PMID 31566307) PF-ILD −80.8 vs −187.8 mL/yr; autoimmune-ILD subgroup +104.0 mL/yr (Wells 2020 PMID 32145830). ADD-ON to immunosuppression (not a replacement) for SSc-ILD or any CTD-ILD meeting ATS/ERS 2022 PPF criteria. Diarrhoea (loperamide + dose-reduce 150→100 BID); hepatotoxicity; bleeding/ATE risk — caution on full anticoagulation; CYP3A4/P-gp substrate |
| prednisone | lowest effective dose; KEEP <15 mg/day prednisone-equiv in SSc (renal-crisis precipitant) | PO | once daily | Background/bridge anti-inflammatory for inflammatory CTD-ILD (IIM, anti-synthetase, NSIP with inflammation, SLE/MCTD/Sjögren). SSc CAUTION: moderate-high dose glucocorticoid (prednisone-equiv >15 mg/day), especially in early diffuse cutaneous SSc / RNA-pol-III+, is a SCLERODERMA RENAL CRISIS precipitant — use lowest effective dose, monitor BP + creatinine closely, and prefer steroid-sparing immunosuppression in SSc |
| methylprednisolone | 500–1000 mg IV daily ×3 (pulse) then high-dose oral taper — anti-MDA5 RP-ILD / severe acute IIM-ILD | IV | pulse ×3 then transition to oral with slow taper over months | High-dose pulse glucocorticoid is a component of the anti-MDA5 RP-ILD combination regimen (Tsuji 2020 PMID 31524333 — high-dose GC + tacrolimus + IV CYC). Taper over months guided by ferritin/HRCT/PFT response (encoded here in rationale/monitoring — `taper_plan` is not a _types.ts field). AVOID high-dose pulse as first move in SSc-dominant disease (renal-crisis risk) |
| tacrolimus (anti-MDA5 RP-ILD combination component) | PO titrated to trough 5–10 ng/mL, as part of up-front combination with high-dose GC + IV CYC | PO | BID titrated to trough | Special-pop: anti-MDA5 RP-ILD EMERGENCY branch — Tsuji 2020 (PMID 31524333) up-front combination (high-dose GC + tacrolimus + IV CYC, ± plasmapheresis if worsening) gave 6-mo survival 89% vs 33% for step-up therapy (P<0.0001). TIME-CRITICAL: combination must start early (IV CYC given ~20 days earlier than step-up). Intensive opportunistic-infection surveillance (frequent CMV reactivation reported); PJP prophylaxis |
| mycophenolate mofetil (SSc steroid-sparing — renal-crisis caution) | 500 mg BID → target 1500 mg BID; minimise concurrent glucocorticoid | PO | BID | Special-pop: SSc branch — SSc-ILD is the leading cause of SSc-related death; MMF is the preferred steroid-sparing first-line (SLS II PMID 27469583). Because moderate-high glucocorticoid precipitates scleroderma renal crisis (esp. early dcSSc / RNA-pol-III+), build the regimen around steroid-sparing IS ± nintedanib add-on and keep any glucocorticoid <15 mg/day prednisone-equiv with BP/creatinine surveillance |
| RA-ILD methotrexate-pneumotoxicity disambiguation + MTX withdrawal | hold/withdraw MTX; distinguish MTX pneumonitis from RA-ILD progression (temporal relation, BAL, HRCT pattern); RA-ILD is often UIP | n/a | at presentation and on any respiratory change in RA on MTX | Special-pop: RA-ILD branch — methotrexate pneumotoxicity is a key confounder; new respiratory disease in RA-on-MTX requires disambiguating drug-induced pneumonitis (often reversible on withdrawal) from progressive RA-ILD. RA-ILD is the notable UIP-predominant CTD-ILD (worse prognosis) → if UIP/PPF, antifibrotic add-on (nintedanib INBUILD PMID 31566307) is relevant alongside RA-directed therapy |
| pregnancy — switch off teratogenic immunosuppression | discontinue MMF and cyclophosphamide pre-conception; switch to pregnancy-compatible IS (e.g., azathioprine or a calcineurin inhibitor) with rheumatology co-management | n/a | pre-conception planning and throughout pregnancy | Special-pop: pregnancy branch — mycophenolate mofetil and cyclophosphamide are TERATOGENIC and CONTRAINDICATED in pregnancy (MMF REMS; CYC fetotoxic/gonadotoxic). Plan ahead: stop teratogenic agents before conception, bridge with a pregnancy-compatible immunosuppressant, and co-manage CTD activity with rheumatology/MFM |
| nintedanib 100 mg BID (hepatic impairment — Child-Pugh A; AVOID Child-Pugh B/C) | 100 mg PO BID (reduced) | PO | BID with food | Special-pop: hepatic/renal-dosing branch — nintedanib Child-Pugh A reduce to 100 mg BID; NOT recommended Child-Pugh B/C (DailyMed label). MMF/CYC require renal-function-aware dosing and intensified CBC/LFT surveillance; choose the best-tolerated combination with tighter monitoring when hepatic/renal impairment coexists |
Plan: CTD-ILD treat-the-CTD immunosuppression + antifibrotic add-on — ACR/CHEST 2023 + ATS/ERS PPF 2022
Contact your care team if any of the following happen:
Call 911 or go to the nearest emergency room right away if you have:
Rheumatology + pulmonology ILD co-clinic q3–6 mo, PPF re-assessment driving antifibrotic add-on, transplant referral for progressive refractory disease, vaccination, pregnancy planning (switch off teratogenic CYC/MMF pre-conception), comorbidity sweep (PH-ILD, GERD-aspiration in SSc, lung-cancer surveillance), palliative integration for advanced disease (ACR/CHEST 2023)
Guideline: 2023 ACR/CHEST Guideline for Screening & Monitoring of ILD in people with SARDs; ATS/ERS/JRS/ALAT 2022 IPF update + Progressive Pulmonary Fibrosis Guideline