Table 3.
Evidence of efficacy for the use of conventional and biologic DMARDs in SS with childhood onset
| Treatment | Reference | Acute symptoms/signs associated with SS targeted by treatment | Response | Background medications | Symptoms/signs targeted by background medications | Response |
|---|---|---|---|---|---|---|
| MTX | Hamzaoui et al., 2010 [18] | Arthritis | Excellent response. Stopped following diagnosis of SS and maintained on low-dose corticosteroids | Low-dose corticosteroids | Uveitis, maintenance (following MTX) | Good control. Clinically stable |
| De Oliveira et al. 2011 [35] | Myalgia and arthralgia (very low dose 2.5 mg weekly associated with oral methylprednisolone) | No mention of treatment response for methylprednisolone and MTX | Oral methylprednisolone 9 mg every 48 h. 1% neutral sodium fluoride every 3 months since diagnosis | Myalgia and arthralgia, oral dryness | At 6 year follow-up, patient has well-controlled oral health | |
| Ohlsson et al., 2006 [36] | Arthritis, dRTA | No details provided | HCQ. No further information on treatments | NA | NA | |
| Civilibal et al., 2007 [33] | Severe arthralgia | Symptoms resolved at 6 month follow-up | Methylprednisolone (1 mg/kg/day) | Local oedema and purpura, bilateral parotid swelling | 6 months after discharge the patient had only one episode of parotid swelling; local oedema and purpura disappeared completely | |
| MMF | Pessler et al., 2006 [21] | Primary SS complicated with overt dRTA | No mention of treatment response | Electrolyte supplementation | Same manifestations | Not available |
| CYC | Berman et al., 1990 [25] | Optic neuropathy and CNS involvement associated with primary SS | Visual acuity improved. Patient stable with no new cerebral infarcts | Oral corticosteroids followed by i.v. steroids in combination with i.v. CYC therapy | Same manifestations | As mentioned |
| Gmuca et al., 2017 [29] | NMOSD | No mention of treatment response in case 1. Visual symptoms worsened in case 2 following treatment and thus the patient received apheresis and RTX | Case 1: i.v. methylprednisolone, RTX in association with CYC, apheresis | Same manifestations | As mentioned | |
| Case 2: HCQ, i.v. methylprednisolone, CYC, switched to mycophenolate as maintenance | ||||||
| Zhang et al., 2007 [39] | SS associated with pulmonary hypertension | At 1 month follow-up, exertional dyspnoea improved dramatically (assessed by walk test). Patient remained stable after prednisolone was tapered and diltiazem was stopped | Prednisolone (0.5 mg/kg/day then gradually tapered), diltiazem, anticoagulant therapy | Same manifestations | As mentioned | |
| Kobayashi et al., 1996 [14] | SS secondary to SLE, membranous and mesangial glomerulonephritis (lupus nephritis class 2, 3) and interstitial nephritis | Good response to treatment; 24 h urinary excretion of protein decreased. Patient’s condition and renal function remained stable during 7 years of follow-up | Methylprednisolone orally followed by prednisolone orally | Initially presented with arthralgia, RP, sicca symptoms, photophobia, facial rash and recurrent parotitis | Good response. Sicca symptoms resolved without using artificial tear or saliva | |
| Ciclosporin | Skalova et al., 2008 [40] | SS associated with hypokalaemia paralysis | Good response | Methylprednisolone (4 mg every other day), potassium chloride (2.5 g/day), Shohl’s solution (9 ml twice daily) | Same manifestations | As mentioned |
| AZA | Bogdanovic et al., 2013 [46] | dRTA/TIN | Significant improvement at 6 months follow-up | Potassium citrate (for dRTA), prednisone (1 mg/kg/day) for 6 months then tapered to 0.5–0.25 mg/kg/day (for TIN). After 3.5 years, MMF replaced AZA for several months | Same manifestations | At 6 years follow-up there was no evidence of xerostomia, xerophthalmia or any other SS-related symptoms |
| Singer et al., 2008 [11] | SS overlapping with SLE with autoimmune hepatitis | Improvement | HCQ | Not specified | Not specified | |
| Biologic treatments | ||||||
| IVIG | Hamzaoui et al., 2010 [18] | Hepatitis, myositis, pericarditis, oral dryness | Clinically stable | Corticosteroids (short course) | Not specified | Not specified |
| Etanercept | Pessler et al., 2006 [21] | Arthritis | At the 4 year follow-up, arthritis responded well to etanercept (disappearance of tender and swollen joints) | HCQ (200 mg daily), MTX (25 mg s.c. weekly) | Renal tubular dysfunction | Normal urinalyses and serum creatinine levels but unchanged renal tubular dysfunction (evidenced by stable requirements for oral sodium citrate (3 mEq/kg/24 h), potassium (3 mEq/kg/24 h) and phosphate supplementation) |
| Infliximab switched to etanercept because of loss of response | Pessler et al., 2006 [34] (likely the same case as reported in the paper above) | Chronic polyarthritis | Initial good response to infliximab, loss of response after 7 months despite dose increase and 3 weeks of infliximab administration. Good response to etanercept after 18 months | NSAIDs, corticosteroids, MTX (0.5 mg/kg once weekly s.c.) and topical steroid eye drops for presumed JRA with uveitis | Xerostomia, uveitis, optic neuritis, RTA | Systemic symptoms developed during treatment with infliximab and not influenced by subsequent treatment with etanercept |
| Rituximab | Tesher et al., 2019 [22] | MALT lymphoma | Both patients achieved remission of MALT lymphoma, with one case having no recurrence of symptoms associated with SS at the 2 year follow-up | Case 1: additional pulsed 1 g i.v. methylprednisolone, HCQ daily | Medication mainly targeted at MALT | As mentioned |
| Case 2: parotidectomy; bendamustine after a course of RTX (due to anaphylaxis to RTX) followed by HCQ monotherapy | ||||||
| Kornitzer et al., 2016 [26] | NMOSD | Clinically improved but not clear if this was related to RTX treatment. Only residual subtle right-sided weakness and mild abducens and facial nerve weakness on examination 3 years after presentation | NA | NA | NA | |
| Hammett et al., 2020 [20] | Psychosis | Psychiatric symptoms improved with RTX infusions in all four patients (at 4–6 month intervals). One patient allergic to RTX was switched to obinutuzumab with maintained benefit | Case 1: pulse methylprednisolone 1000 mg daily for 3 days followed by a prednisone taper over 24 weeks, olanzapine | Various psychiatric manifestations including: insomnia; increase in hallucinations, tics and anxiety after starting an oral contraceptive; catatonia; suicidal ideation; fluctuating coherence; delusions; slow psychomotor responses and echolalia, echopraxia and posturing | All patients improved and were able to go back to a normal life | |
| Case 2: aripiprazole and obinutuzumab, as the patient developed an allergic reaction to RTX | ||||||
| Case 3: MMF 1500 mg twice a day, oral prednisone 2.5 mg/day, risperidone along with benztropine and clonazepam | ||||||
| Case 4: pulse methylprednisolone for 3 days followed by oral prednisone taper, HCQ 200 mg daily | ||||||
| Tocilizumab | Marino et al., 2017 [53] | NMOSD | Neurological manifestations: left vision loss, right hemiparesis and lethargy not well controlled by RTX and i.v. methylprednisolone | No concomitant medication. Previous treatment with CYC and RTX followed by MMF. Despite complete depletion of CD19+ B lymphocytes, the patient continued flaring | Same manifestations | Clinical remission |
AIH: autoimmune hepatitis; NA: not available.