Early intervention in psoriasis and immune-mediated inflammatory diseases: A hypothesis paper

Figures & data

Table 1. Summary of key studies assessing early intervention with biologics in Crohn’s disease (CD).

	Treatment	Patients	Key outcomes
D’Haens (23)	Step-up: corticosteroids then AZA plus IFX (n = 66) Top-down: AZA plus IFX (n = 67)	133 corticosteroid-naïve CD patients	Corticosteroid-free remission at week 52 in 61.5% of top-down and 42.2% of step-up patients (95% CI 2.4–36.3, p = 0.278) Top-down treatment led to more rapid reductions in CRP at week 10 than step-up (−15.0 mg/l versus −4.2 mg/l, respectively; p = 0.0244)
Colombel (24)	AZA plus placebo (n = 170) IFX plus placebo (n = 169) AZA plus IFX (n = 169)	508 patients with moderate-to-severe CD naïve of immunosuppressive or biologic therapy	Corticosteroid-free clinical remission at week 26 in 31% with AZA plus placebo, 44% with IFX plus placebo (p = 0.009 versus AZA plus placebo), and in 57% with IFX plus AZA (p < 0.001 versus AZA plus placebo, p = 0.022 versus IFX plus placebo) Higher CRP levels at baseline were associated with the achievement of remission during treatment with AZA plus IFX

6-MP, 6-mercaptopurine; AZA, azathioprine; CRP, C-reactive protein; IFX, infliximab.

Table 2. Summary of key studies assessing early intervention with biologics in rheumatoid arthritis (RA).

	Treatment	Patients	Key outcomes
Breedveld (14)	Adalimumab plus MTX Adalimumab MTX	799 MTX-naïve RA patients	At 52 weeks ACR50 achieved by 62% of MTX plus adalimumab patients (p < 0.001 versus monotherapy), 46% with MTX, and 41% with adalimumab Significantly less radiographic progression observed among patients in the combination arm versus monotherapy (p ≤ 0.002)
Bejarano (15) Jamal (16) Keystone (17)	Adalimumab 40 mg plus MTX (n = 207) Adalimumab 20 mg plus MTX (n = 212) MTX plus placebo (n = 200)	619 patients with MTX-refractory RA	At week 24 ACR20 in 63% treated with adalimumab 40 mg, 61% with adalimumab 20 mg, and 30% for placebo (p ≤ 0.001 for both comparisons) ACR20 at 52 weeks achieved by 59%, 55%, and 24% of patients, respectively (p ≤ 0.001 for both comparisons) Adalimumab plus MTX led to significantly less radiographic progression at week 52 compared with placebo (p ≤ 0.001 for both comparisons) IFX plus MTX led to more ACR20, 50, and 70 responses in early RA IFX plus MTX led to significantly less job loss in patients with early RA
Saleem (101)	Adalimumab plus MTX (n = 22) Infliximab plus MTX (n = 20) Etanercept plus MTX (n = 5) Patients discontinued treatment with the TNF blocking drug and continued MTX for 24 months’ follow-up	47 patients with RA in remission following treatment with MTX and TNF blocker therapy	Timing of treatment was the main predictor of successful cessation of TNF blocking agents: 59% of patients receiving a TNF inhibitor plus MTX as a first line treatment (“early treatment group”) sustained remission compared with 15% in the delayed treatment group (p > 0.003)
Goekoop-Ruiterman (18)	Sequential monotherapy (n = 126) Step-up combination (n = 121) Initial combination (n = 133) Initial IFX plus MTX (n = 128)	508 patients with early RA (<2 year duration)	Through 3 months, HAQ scores were significantly improved in the initial combination and initial IFX plus MTX groups (p < 0.001 for both). difference was sustained through one year of treatment (p = 0.009 for both) Accompanied by significant improvements in radiographic progression in the initial combination and initial IFX plus MTX groups (p < 0.001 for both)
St Clair (19)	MTX plus placebo (n = 298) MTX plus IFX 3 mg/kg (n = 373) MTX plus 6 mg/kg IFX (n = 378)	1049 MTX- and IFX-naïve RA patients	At week 54 ACR improvement was significantly higher in the MTX-IFX 3 mg/kg and MTX-IFX 6 mg/kg groups versus placebo (38.9%, 46.7%, and 26.4%, respectively; p < 0.001 for both) MTX-IFX 3 mg/kg and MTX-IFX 6 mg/kg also led to less radiographic progression that placebo (p < 0.001 for both)
Emery (20)	MTX (n = 268) MTX plus etanercept 50 mg (n = 274)	542 MTX-naïve patients with moderate-to-severe RA	Clinical remission achieved by 50% (95% CI 44–56%) of combined treatment patients and 28% (95% CI 23–33%) MTX patients (p < 0.0001) No radiographic progression occurred in 80% (75–85%) and 59% (53–65%) of MTX–etanercept and MTX-treated patients, respectively
Klareskog (21)	Etanercept 25 mg (n = 223) MTX (n = 228) MTX plus etanercept (n = 231)	686 patients with active RA	The ACR AUC at 24 weeks was 18.3%-years (95% CI 17.1–19.6) for MTX–etanercept, 14.7%-years (13.5–16.0) for etanercept (p < 0.0001), and 12.2%-years (11.0–13.4) for MTX (p < 0.0001) MTX–etanercept led to significant retardation of joint damage (p < 0.0001 versus MTX and p = 0.0006 versus etanercept)
Emery (22)	MTX plus placebo (n = 160) Golimumab 100 mg plus placebo (n = 159) Golimumab 50 mg plus MTX (n = 159) Golimumab 100 mg plus MTX (n = 159)	637 MTX-naïve RA patients	Compared to MTX alone, ACR50 responses were significantly better in the combination groups (29.4% versus 38.5%, respectively; p = 0.049) and for the golimumab 50 mg plus MTX group (40.5%, p = 0.038); but not for the golimumab 100 mg plus MTX group (36.5%, p = 0.177) The golimumab plus MTX combination led to significantly better response/remission rates and DAS versus placebo

ACR20, American College of Rheumatology-defined 20% improvement in symptoms; ACR50, American College of Rheumatology-defined 50% improvement in symptoms; AUC, area under the curve; DAS, disease activity score; HAQ, health-assessment questionnaire; IFX, infliximab; MTX, methotrexate.

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