Clinical Deep-Dive · Rheumatoid Arthritis

NORD-STAR: Abatacept Achieved 59.3% CDAI Remission in Early RA

August 31, 2026

Randomized patients

812 [1]

Week 48 CDAI remission — abatacept

59.3% [1]

Week 48 CDAI remission — certolizumab pegol

52.3% [1]

Week 48 CDAI remission — tocilizumab

51.9% [1]

Week 48 CDAI remission — active conventional therapy

39.2% [1]

Abatacept vs active conventional therapy adjusted difference

+20.1% (p<0.001) [1]

Serious adverse events — abatacept

8.3% [1]

ORENCIA label effective date

2025-11-13 [3]

Clinical Perspective

The NORD‑STAR trial compared methotrexate plus active conventional therapy against methotrexate plus certolizumab pegol, abatacept, or tocilizumab and reported higher week‑48 CDAI remission rates with abatacept and certolizumab pegol versus active conventional therapy ^[1]. The trial data support consideration of abatacept or certolizumab pegol as methotrexate‑combination options associated with higher CDAI remission rates at week 48 compared with the specific active conventional therapy protocol used in NORD‑STAR ^[1]. Which patient‑level clinical characteristics best predict durable radiographic and functional advantages from abatacept versus other mechanisms in early RA remains to be defined?

Dr. Deepak Nair, MBBS, MD (General Medicine), DM (Clinical Immunology & Rheumatology) · Rheumatology

The investigator‑initiated NORD‑STAR trial randomized patients with treatment‑naïve early rheumatoid arthritis (RA) and moderate‑to‑severe disease activity to methotrexate plus one of four strategies and reported adjusted week‑48 Clinical Disease Activity Index (CDAI) remission rates of 59.3% for abatacept, 52.3% for certolizumab pegol, 51.9% for tocilizumab, and 39.2% for active conventional therapy ^[1]. Compared with active conventional therapy, the adjusted difference in CDAI remission at week 48 was +20.1% for abatacept (p<0.001) and +13.1% for certolizumab pegol (p=0.021); the adjusted difference for tocilizumab was +12.7% (p=0.030) ^[1].

Clinical Context

The optimal first‑line treatment strategy in early RA remains debated; NORD‑STAR was designed to compare methotrexate combined with active conventional therapy against methotrexate combined with three biologic agents representing distinct mechanisms of action ^[1]. The trial enrolled patients described as treatment‑naïve early RA with moderate‑severe disease activity and randomized them 1:1:1:1 to the four treatment arms to assess clinical and radiographic outcomes at 48 weeks ^[1]. Coprimary endpoints were clinical remission measured by CDAI (CDAI ≤2.8) at week 48 and change in radiographic van der Heijde‑modified Sharp Score at week 48, with analyses adjusted for sex, anticitrullinated protein antibody status, and country ^[1]. Radiographic progression was reported as low across groups without differences between treatment arms in the trial report ^[1].

In parallel to trial data on biologic choices in early RA, regulatory safety communications affecting other drug classes used in inflammatory arthritis are relevant to treatment selection: the FDA concluded from a large randomized safety trial that tofacitinib (Xeljanz/Xeljanz XR) was associated with increased risk of serious heart‑related events, cancer, blood clots, and death versus tumor necrosis factor (TNF) blockers in patients with RA, and the agency required labeling warnings and limited uses for JAK inhibitors in certain patients ^[2]. The ORENCIA (abatacept) prescribing information describes abatacept as a selective T‑cell costimulation modulator indicated for adult patients with moderately to severely active RA, and provides dosing regimens for intravenous and subcutaneous administration in RA and other indications ^[3].

Key Findings

The NORD‑STAR trial showed abatacept achieved an adjusted CDAI remission rate of 59.3% at week 48 versus 39.2% with active conventional therapy (adjusted difference +20.1%, p<0.001) in patients with treatment‑naïve early RA ^[1].
The trial showed certolizumab pegol achieved an adjusted CDAI remission rate of 52.3% at week 48 versus 39.2% with active conventional therapy (adjusted difference +13.1%, p=0.021) in the same population ^[1].
Tocilizumab produced an adjusted CDAI remission rate of 51.9% at week 48 versus 39.2% with active conventional therapy (adjusted difference +12.7%, p=0.030) in the trial population; the report presents the point estimate and p‑value for the comparison with active conventional therapy ^[1].
Coprimary radiographic endpoint findings: radiographic progression was described as low across groups and without between‑group differences in the reported 48‑week radiographic analyses using the van der Heijde‑modified Sharp Score ^[1].
Key secondary clinical outcomes were consistently reported as better in the biological treatment groups compared with active conventional therapy, according to the trial publication ^[1].
Serious adverse event (SAE) proportions reported in NORD‑STAR were abatacept 8.3%, certolizumab pegol 12.4%, tocilizumab 9.2%, and active conventional therapy 10.7% ^[1].
Abatacept mechanism of action: abatacept is a selective T‑cell costimulation modulator that binds to CD80 and CD86, blocking interaction with CD28 and thereby inhibiting T‑cell activation; in vitro abatacept decreases T‑cell proliferation and inhibits production of TNFα, interferon‑γ, and interleukin‑2 ^[3].
Abatacept clinical development and formulations: the ORENCIA label summarizes randomized, double‑blind, controlled studies of both intravenous and subcutaneous abatacept in adult RA and reports that subcutaneous ORENCIA 125 mg weekly (consult current prescribing information for full dosing guidance) was compared with intravenous dosing in a randomized non‑inferiority study (Study SC‑1) demonstrating non‑inferiority for ACR20 at 6 months per the prespecified margin ^[3]. (consult current prescribing information for full dosing guidance) ^[3]
Refer to prescribing information for full dosing guidance ^[3].
Labeling instructions and usage limits: ORENCIA is indicated for adult patients with moderately to severely active RA and the label states that concomitant use of ORENCIA with other immunosuppressives (for example, biologic DMARDs or JAK inhibitors) is not recommended ^[3].

Safety & Tolerability

In NORD‑STAR, proportions of patients with serious adverse events were abatacept 8.3%, certolizumab pegol 12.4%, tocilizumab 9.2%, and active conventional therapy 10.7% ^[1]; the FDA concluded that tofacitinib (Xeljanz/Xeljanz XR) was associated with increased risk of serious heart‑related events, cancer, blood clots, and death versus TNF blockers and required labeling warnings and limited uses for JAK inhibitors in certain patients ^[2]; the ORENCIA prescribing information states that concomitant use of ORENCIA with other immunosuppressives such as biologic DMARDs or JAK inhibitors is not recommended ^[3].

Study Design

The NORD‑STAR trial was an investigator‑initiated, randomized, blinded‑assessor study that enrolled patients with treatment‑naïve early RA and moderate‑to‑severe disease activity and randomized patients 1:1:1:1 to methotrexate combined with either active conventional therapy (defined as oral prednisolone tapered and discontinued at week 36 or sulfasalazine, hydroxychloroquine and intra‑articular glucocorticoids), certolizumab pegol, abatacept, or tocilizumab ^[1]. Coprimary endpoints were week‑48 Clinical Disease Activity Index (CDAI) remission (CDAI ≤2.8) and change in van der Heijde‑modified Sharp Score for radiographic progression; statistical analyses used logistic regression and analysis of covariance adjusted for sex, anticitrullinated protein antibody status, and country, with Bonferroni's and Dunnett's procedures applied for multiple testing and a significance level of 0.025 as specified in the report ^[1]. The publication reports adjusted CDAI remission rates at week 48 for each arm and adjusted differences versus active conventional therapy with associated p‑values for those comparisons ^[1]. Key secondary clinical outcomes are described in the trial report as consistently better in the biological groups; radiographic progression at week 48 was reported as low without between‑group differences ^[1]. Details such as long‑term extension outcomes beyond 48 weeks or health economic analyses were not available in the provided source excerpts ^[1].

FAQ

Q1 What did the NORD‑STAR trial show?

The NORD‑STAR trial randomized patients with treatment‑naïve early RA to methotrexate plus active conventional therapy, certolizumab pegol, abatacept, or tocilizumab and reported adjusted CDAI remission rates at week 48 of 59.3% for abatacept, 52.3% for certolizumab pegol, 51.9% for tocilizumab, and 39.2% for active conventional therapy. Compared with active conventional therapy, adjusted differences in CDAI remission were +20.1% for abatacept (p<0.001), +13.1% for certolizumab pegol (p=0.021), and +12.7% for tocilizumab (p=0.030).

Q2 Who was enrolled in the NORD‑STAR trial?

NORD‑STAR enrolled patients described as treatment‑naïve early rheumatoid arthritis patients with moderate‑to‑severe disease activity and randomized patients 1:1:1:1 to the four treatment strategies. The active conventional therapy arm included methotrexate plus either a tapered oral prednisolone regimen discontinued at week 36 or a combination of sulfasalazine, hydroxychloroquine and intra‑articular glucocorticoid injections in swollen joints, while the other arms combined methotrexate with certolizumab pegol, abatacept, or tocilizumab.

Q3 What were the side effects in the NORD‑STAR trial?

The trial report provides proportions of patients with serious adverse events as abatacept 8.3%, certolizumab pegol 12.4%, tocilizumab 9.2%, and active conventional therapy 10.7%.

NORD-STAR: Abatacept Achieved 59.3% CDAI Remission in Early RA

Direct Clinical Takeaway & Evidence Summary

NORD-STAR: Abatacept Achieved 59.3% CDAI Remission in Early RA

Clinical Perspective

Clinical Context

Key Findings

Safety & Tolerability

Study Design

FAQ

References

Get weekly clinical updates for Rheumatoid Arthritis in your inbox.

Verified HCP Portal