Summary of published trials to prevent/delay incident clinical RA in high-risk populationsa.
| Study, Year | Inclusion Criteria | Study Design and Intervention | Primary Outcome | Results |
|---|---|---|---|---|
| Bos, 201085 | RF and/or ACPA+; SE+; arthralgia | RCT; dexamethasone 100 mg IM × 2 doses vs PBO | Incident clinical IA | 17/83 (21%) developed IA after a median follow-up of 26 mos; no difference between arms (dexamethasone 21% vs PBO 20%). Dexamethasone use associated with decreased autoantibody levels. |
| Gerlag, 2019 (PRAIRI)86 | RF and ACPA+; CRP > 0.6 mg/L; arthralgia | RCT; RTX 1000 mg × 1 dose (and steroid) vs PBO | Incident clinical IA | 30/81 (37%) developed IA after a mean follow-up of 29 mos; no significant difference in overall rates of IA between arms (RTX 14/41 [34%], PBO 14/40 [40%]); RTX associated with delay of IA onset. |
| van Boheemen, 2021 (STAPRA)87 | RF and ACPA+ or ACPA > 3 × ULN; arthralgia | RCT; atorvastatin 40 mg/d × 3 yrs vs PBO | Incident clinical IA | 15/62 (24%) developed IA after a median follow-up of 14 mos; no significant difference between arms (atorvastatin 9/31 [29%] vs PBO 6/31 [19%]). |
| Krijbolder, 2022 (TREAT EARLIER)88 | Arthralgia and MRI evidence of joint inflammation in absence of clinical swollen joint; RF/ACPA not required for inclusion although 33 of participants were RF and/or ACPA+ | RCT; methylprednisolone 120 mg × 1 dose and MTX up to 25 mg/wk × 1 yr vs PBO; 1-yr % postdrug follow-up | RA by 2010 criteria present at 2 timepoints 2 wks apart | 44/236 (19%) developed RA over the 2 yrs of the trial; no significant differences between arms (MTX 23/119 [19%], PBO 21/117 [18%]; decreased measures of physical function, pain, and MRI inflammation in MTX-treated group. The highest rate of RA development was within ACPA+ individuals (27/54 [50%]), although there was no significant difference in rates between arms at 2 yrs. |
| Rech, 2021, 2022 (ARIAA)92,93,b | ACPA+ and MRI evidence of joint inflammation | RCT; ABA 125 mg SC weekly × 6 mos vs PBO; 1-yr postdrug follow-up | MRI inflammatory parameter improvement; clinical RA | In preliminary analyses, at 18 mos there was significant MRI improvement in ABA arm compared to PBO (28/49 [57%] vs 14/49 [29%]). At 18 mos there was also significantly less progression to clinical RA in ABA arm compared to PBO (17/49 [35%] vs 28/49 [57%]). |
| Deane, 2022 (StopRA)91,b | ACPA ≥ 2 × ULN | RCT; HCQ 200-400 mg/d × 1 yr vs PBO; 2 yrs postdrug follow-up | RA by 2010 criteria | In preliminary analyses, 43/144 (30%) developed RA over the 3 yrs of the study; no significant differences between arms (24/71 [34%], PBO 26/73 [36%]); trial halted and final analyses pending. |
| Cope, 2023 (APIPPRA) 95,b | ACPA+, RF+ or ACPA ≥ 3 × ULN; arthralgia | RCT; ABA 125 mg weekly injection × 1 yr vs PBO; 1-yr postdrug follow-up | RA by 2010 criteria | In preliminary analyses, at 2 yrs, 65/213 (~31%) of participants developed RA by 2010 criteria; 25% in ABA arm and 37% in PBO arm. This resulted in differences in mean arthritis-free survival time between arms of ~99 days (P = 0.002). |
↵a Although the inclusion criteria varied across studies, in all studies, no subjects could have clinical RA at baseline, and the primary endpoint included the development of examination evidence of IA.
↵b The results from ARIAA, StopRA, and APIPPRA have only been presented in abstract form. ABA: abatacept; ACPA: anticitrullinated protein antibodies; APIPPRA: Arthritis Prevention in the Pre-Clinical Phase of RA With Abatacept; ARIAA: Abatacept Reversing Subclinical Inflammation as Measured by MRI in ACPA Positive Arthralgia; CRP: C-reactive protein; HCQ: hydroxychloroquine; IA: inflammatory arthritis; IM: intramuscular; MRI: magnetic resonance imaging; MTX: methotrexate; PBO: placebo; PRAIRI: Prevention of Clinically Manifest Rheumatoid Arthritis by B Cell Directed Therapy in the Earliest Phase of the Disease; RA: rheumatoid arthritis; RCT: randomized controlled trial; RF: rheumatoid factor; RTX: rituximab; SE: shared epitope; SC: subcutaneous; STAPRA: Statins to Prevent Rheumatoid Arthritis; StopRA: Strategy to prevent the Onset of Clinically-Apparent Rheumatoid Arthritis; ULN: upper limit of normal.