What is the rate of clinical response to Rinvoq (upadacitinib) in patients with moderate to severe rheumatoid arthritis?

Clinical Response Rates to Rinvoq (Upadacitinib)

Rheumatoid Arthritis

In patients with moderate to severe rheumatoid arthritis, Rinvoq 15 mg once daily achieves ACR20 response rates of 65-71% at 12 weeks, with clinical remission rates of 26-34% at 8-12 weeks, representing substantially higher efficacy than placebo or methotrexate monotherapy. 1, 2

Response Rates by Patient Population

Methotrexate-Inadequate Responders:

• ACR20 response: 71% at week 12 (vs 36% placebo; absolute difference 34%) 1
• ACR50 response: 45% at week 12 (vs 15% placebo) 1
• ACR70 response: 25% at week 12 (vs 5% placebo) 1
• Clinical remission (DAS28-CRP <2.6): 28% at week 12 1

Biologic DMARD-Inadequate Responders:

• ACR20 response: 65% at week 12 (vs 28% placebo; absolute difference 36%) 1, 2
• ACR50 response: 34% at week 12 (vs 12% placebo) 1
• ACR70 response: 12% at week 12 (vs 7% placebo) 1
• DAS28-CRP ≤3.2: 43% at week 12 (vs 14% placebo) 2

Methotrexate-Naïve Patients (Monotherapy):

• ACR20 response: 76% at week 12 (vs 54% methotrexate; absolute difference 22%) 1
• ACR50 response: 52% at week 12 (vs 28% methotrexate) 1
• ACR70 response: 32% at week 12 (vs 14% methotrexate) 1

Conventional DMARD-Inadequate Responders:

• ACR20 response: 64% at week 12 (vs 36% placebo) 1
• ACR50 response: 38% at week 12 (vs 15% placebo) 1
• ACR70 response: 21% at week 12 (vs 6% placebo) 1

Time to Response

• Rapid onset of action: ACR20 response rates separate from placebo as early as week 1 in both conventional DMARD-IR and biologic DMARD-IR populations 1
• Sustained efficacy: Response rates are maintained through 84 weeks of continuous treatment in Japanese patients, with ACR20 rates of 77.6% at week 84 3

Comparative Efficacy

• Superior to adalimumab: In head-to-head comparison, upadacitinib 15 mg plus methotrexate demonstrated superior ACR20/50/70 response rates compared to adalimumab plus methotrexate, particularly for patient-reported outcomes 4, 5

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Ulcerative Colitis

For moderate to severe ulcerative colitis, upadacitinib 45 mg once daily induction therapy achieves clinical remission in 26-34% of patients at week 8, with maintenance therapy (15 mg or 30 mg) achieving clinical remission in 42-52% at week 52. 4, 6

Induction Response Rates (45 mg once daily for 8 weeks)

• Clinical remission: 26% (U-ACHIEVE) and 34% (U-ACCOMPLISH) vs 4-5% placebo 4, 6
• Absolute benefit: 21.6-29.0% over placebo 4
• Endoscopic response: 45.5% (U-ACHIEVE) and 34.6% (U-ACCOMPLISH) vs 3.5-13.1% placebo 6

Maintenance Response Rates (Week 52)

Upadacitinib 15 mg once daily:

• Clinical remission: 42% vs 12% placebo (absolute difference 30.7%) 4, 6
• Endoscopic response: 27.6% vs 7.3% placebo 6

Upadacitinib 30 mg once daily:

• Clinical remission: 52% vs 12% placebo (absolute difference 39.0%) 4, 6
• Endoscopic response: 40.1% vs 7.3% placebo 6

Extended Induction for Non-Responders

• Nearly 48% of patients who failed initial 8-week induction responded to an additional 8 weeks of therapy, with more than half maintaining clinical response at 1 year 4

Comparative Efficacy in UC

Network meta-analysis positioning (biologic-naïve patients):

• Upadacitinib ranks as a HIGHER efficacy medication alongside infliximab, vedolizumab, ozanimod, etrasimod, risankizumab, and guselkumab 4
• Risk difference for clinical remission: 65.25% (95% CI 19.7-100.0) with highest P-score of 0.93 in network meta-analysis 4
• Relative risk for clinical remission: 14.05 (95% CI 4.94-43.94) vs placebo 4

Biologic-exposed patients:

• Upadacitinib demonstrates likely important benefit with moderate certainty evidence compared to other advanced therapies 4
• Relative risk vs filgotinib: 5.19 (95% CI 1.25-21.53) favoring upadacitinib 4

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Crohn's Disease

In moderate to severe Crohn's disease, upadacitinib 45 mg induction achieves clinical remission in 38.9-49.5% at week 12, with maintenance therapy (15 mg or 30 mg) achieving clinical remission in 37.3-47.6% at week 52. 7

Induction Response Rates (45 mg once daily for 12 weeks)

U-EXCEL trial:

• Clinical remission: 49.5% vs 29.1% placebo 7
• Endoscopic response: 45.5% vs 13.1% placebo 7

U-EXCEED trial:

• Clinical remission: 38.9% vs 21.1% placebo 7
• Endoscopic response: 34.6% vs 3.5% placebo 7

Maintenance Response Rates (Week 52)

Upadacitinib 15 mg once daily:

• Clinical remission: 37.3% vs 15.1% placebo 7
• Endoscopic response: 27.6% vs 7.3% placebo 7

Upadacitinib 30 mg once daily:

• Clinical remission: 47.6% vs 15.1% placebo 7
• Endoscopic response: 40.1% vs 7.3% placebo 7

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Psoriatic Arthritis

For psoriatic arthritis, upadacitinib 15 mg demonstrates non-inferiority for ACR20 response compared to adalimumab, while the 30 mg dose shows superiority. 4, 8

• The 15 mg dose is the standard approved dose for psoriatic arthritis 8
• Efficacy has been demonstrated in both conventional DMARD-inadequate responders and TNF inhibitor-inadequate responders 4

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Ankylosing Spondylitis

In active ankylosing spondylitis, upadacitinib 15 mg achieves ASAS 40 response in 52% of patients at week 14 vs 26% placebo, with response observed as early as week 2. 4

• Major improvement in ASDAS: 33% vs 2% placebo at week 12 (for filgotinib 200 mg, similar JAK inhibitor class effect expected) 4
• Significant improvements in MRI spine and sacroiliac joint inflammation 4

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Critical Safety Considerations Affecting Response Assessment

• Herpes zoster rates are elevated with upadacitinib compared to placebo and adalimumab, which may interrupt therapy and affect sustained response 9
• CPK elevations occur more frequently with upadacitinib, requiring monitoring that may impact dose continuation 9
• The 30 mg dose carries higher adverse event rates including gastrointestinal perforations, limiting its use despite higher response rates 9, 7
• FDA boxed warnings apply to all JAK inhibitors based on increased cardiovascular events, thromboembolism, malignancies, and death in patients ≥50 years with cardiovascular risk factors 5, 10