Treatment Options for Still's Disease Save

Jack Cush, MD

Jul 22, 2022 11:31 am

Begin – are you treating “systemic” or “articular” (arthritis) Still’s disease? Most Still’s patients have a dominance of one or the other. With certainty, the right therapy for the right symptoms can be chosen.

Systemic disease: key symptoms/findings include high daily fevers (>102oF), rashes, pleuritis or pericarditis, enlarged liver/spleen/lymph nodes, wt. loss
- Labs: active disease is indicated by very high ESR, CRP, WBC, ferritin levels, aldolase, increased LFTs; with anemia (low Hgb/Hct), low albumin
Articular disease: key symptoms are multiple painful, swollen joints (usually hands, wrists, knees, ankles, feet, shoulders), often with fatigue & stiffness
- Labs: active disease usually has normal WBC, mild anemia, increased ESR or CRP, negative tests for ANA & RF. (Normal: ferritin, albumin, LFTs)

Sequential Drug Use – The goal is to rapidly control of pain and inflammation – this is starts with using “1st Line Therapy”.

1st Line Therapy: start with drugs that act quickly (hours, days). The potential down side of fast-acting drugs may be long-term side effects; this is the case with NSAIDs and steroids; see Best Drugs Table below. With time 1st line drugs are replaced by more long-lasting therapies – “2nd Line Therapy”.
2nd Line Therapy: these drugs are referred to as Disease Modifying Anti-Rheumatic Drugs (DMARDs). DMARDs may be oral pills or injectables and are typically a) slow-acting (weeks to months), b) given chronically (often called “steroid-sparing drugs”), and c) are given to change the underlying disease. “Biologic” DMARDs (injectable or parenteral) are similar to your body’s proteins, and are used to specifically regulate an overactive immune system.

When Not Responding? While most patients respond well to the treatments noted below, some patients may have an incomplete or no response, or become unresponsive to a drug that once worked well. Three key questions need to be answered when the patient is not responding (or refractory): (1) Is this the right diagnosis? (2) Is this Systemic or Articular disease? (3) I there another problem (new diagnosis/complication or medication side effect developing)? Off-Label Use: When poorly responsive or refractory to standard DMARD or biologic therapy, numerous options can be considered. All of these are considered “off-label”, as these treatment options are not FDA approved for use in Still’s disease. Nearly all treatments used in Still’s disease are “off-label” because Still’s is a very rare, for which there are few studies that might lead to FDA approved drugs. Only tocilizumab & canakinumab are FDA approved for use in children (sJIA) and only canakinumab is FDA approved for adult-onset Still’s disease (AOSD). MAS (Macrophage Activation Syndrome): MAS is a severe complication of “systemic” Still’s disease, where uncontrolled, hyper-inflammation can lead to organ damage. MAS is associated with a 10-35% risk of death. MAS should be considered with very high fever, hypotension, altered mental status, very high levels of CRP, liver enzymes, and ferritin (often >10,000), along with a sudden drop in blood counts (leukopenia, lymphopenia, thrombocytopenia). Drugs used to treat MAS include high dose steroids, inhibitors of IL-1 or IL-6, emapalumab, cyclosporine, etoposide or JAK inhibitors.

TREATMENT OPTIONS IN STILL’S DISEASE

Treatment Stage	Systemic Disease	Articular Disease
1st Line Therapy	Prednisone 60 mg/day (or >1mg/kg/day) (Or high doses of IV methylprednisolone)	NSAIDs Low dose Prednisone 5-10 mg/day
2nd Line Therapy	IL-1 inhibitors SC IL-6 inhibitors SC or IV (Methotrexate may be added to above)	Methotrexate or Leflunomide TNF inhibitors SC or IV Canakinumab SC Tocilizumab SC or IV
Refractory Disease Drugs	Methotrexate JAK inhibitors IVIG	JAK inhibitors, Rituximab, Abatacept, Azathioprine Hydroxychloroquine, cyclosporine A

Best Drugs Table

Generic name	Example	Type of Drug	How given	Usual dose	Used to treat:
NSAIDS	Naproxen Ibuprofen Meloxicam	Antiinflammatory	Oral pills	Naproxen: 500mg Ibuprofen 600-800mg Meloxicam 7.5, 15 mg	Joint pain, stiffness, aching, swelling
Prednisone	Low dose Prednisone High dose Prednisone	Corticosteroid Antiinflammatory	Oral pills	Low dose 2.5-10 mg/d High dose 60-80 mg/d	Articular Still’s Systemic Still’s
Methylprednisolone	Solumedrol	Corticosteroid Antiinflammatory	Intravenous	1-2 mg/kg/d	Systemic Still’s MAS
Methotrexate	Rheumatrex	DMARD Antiinflammatory	Oral pills or Subcutaneous injection	7.5-25 mg (Kids: 0.3-0.6 mg/kg)	Articular Still’s Systemic Still’s
Leflunomide	Arava	DMARD Antiinflammatory	Oral Pills	10-20 mg	Articular Still’s
Azathioprine	Imuran	DMARD Immunosuppressive	Oral Pills	50-200 mg (1-2 mg/kg)	Articular Still’s Systemic Still’s
Hydroxychloroquine	Plaquenil	DMARD	Oral pills	200-400 mg (< 5.5 mg/kg)	Articular Still’s
JAK inhibitors	Xeljanz, Olumiant, Rinvoq	DMARD	Oral pills	Xeljanz 11 mg; Rinvoq 15mg; Olumiant 2mg	Articular Still’s
Canakinumab	Ilaris	Interleukin-1 inhibitor	Subcutaneous injection	150-300 mg (4 mg/kg)	Systemic Still’s Articular Still’s
Anakinra	Kineret	Interleukin-1 inhibitor	Subcutaneous injection	100 mg (some 200mg) (1-2 mg/kg)	Systemic Still’s Articular Still’s
Tocilizumab	Actemra	Interleukin-6 inhibitor	Subcutaneous or Intravenous	SC: 162 mg IV: 4-12 mg/kg	Systemic Still’s Articular Still’s
Infliximab	Remicade	TNF inhibitor	Intravenous infusion	3-10 mg/kg	Articular Still’s
Adalimumab	Humira	TNF inhibitor	Subcutaneous injection	40 mg	Articular Still’s
Etanercept	Enbrel	TNF inhibitor	Subcutaneous injection	25 or 50 mg	Articular Still’s
Certolizumab	Cimzia	TNF inhibitor	Subcutaneous injection	200 mg	Articular Still’s
IVIG (IV gammaglobulin)	Gammagard (many brands available)	Immunoglobulins Immunosuppressive	Subcutaneous or Intravenous	1-2 g/kg.	Systemic Still’s
Rituximab	Rituxan	B-cell inhibitor Biologic DMARD	Intravenous infusion	1000 mg	Articular Still’s
Abatacept	Orencia	T-cell inhibitor Biologic DMARD	Subcutaneous or Intravenous	SC: 125 mg IV: 500, 750, 1000mf	Articular Still’s

(Abbreviations: SC-subcutaneous; IV-intravenous; NSAID-nonsteroidal anti-inflammatory drugs; IL-interleukin; LFTs-liver function tests; TB-tuberculosis; BP-blood pressure)