Rinvoq and Velsipity: What Seniors Need to Know About New UC Treatments

Ulcerative colitis (UC), a chronic inflammatory bowel disease causing abdominal pain, bloody diarrhea, and urgency, affects approximately 1.25 million Americans, including many seniors. For older adults, managing UC can be particularly challenging due to comorbidities, reduced immune function, and the burden of complex treatment regimens. Two innovative oral medications, Rinvoq (upadacitinib) and Velsipity (etrasimod), approved by the FDA in 2022 and 2023 respectively, offer new hope for seniors with moderate to severe UC who have not responded to conventional therapies like tumor necrosis factor (TNF) blockers. This article explores Rinvoq and Velsipity’s mechanisms of action—Janus kinase (JAK) inhibition versus sphingosine-1-phosphate (S1P) modulation—their efficacy, why seniors may prefer oral treatments over injections, and essential steps for starting treatment safely.

Understanding UC in Seniors

UC is an autoimmune condition where the immune system attacks the colon’s lining, leading to inflammation and ulcers. Seniors over 65 face unique challenges, including higher risks of complications like infections or cardiovascular events, which can complicate treatment. Traditional UC therapies, such as corticosteroids, immunosuppressants, or injectable biologics (e.g., adalimumab), often require frequent medical visits or self-administration, which can be difficult for seniors with mobility issues or dexterity limitations. The introduction of Rinvoq and Velsipity as oral, once-daily pills addresses these challenges, offering effective alternatives for those intolerant to or unresponsive to TNF blockers.

Rinvoq: A JAK Inhibitor for UC

Rinvoq, developed by AbbVie, is a selective JAK1 inhibitor approved in March 2022 for adults with moderate to severe UC. JAK enzymes (JAK1, JAK2, JAK3, TYK2) are part of the JAK-STAT signaling pathway, which transmits inflammatory cytokine signals inside cells. In UC, overactive JAK signaling drives excessive inflammation, causing symptoms like rectal bleeding and frequent bowel movements. Rinvoq blocks JAK1 with 74-fold selectivity over JAK2 and 58-fold over JAK3, reducing inflammation while minimizing off-target effects like anemia or immune suppression.

Rinvoq’s efficacy was demonstrated in three Phase 3 trials (U-ACHIEVE, U-ACCOMPLISH, NCT03653026). In induction studies, 26–34% of patients receiving 45 mg daily achieved clinical remission (defined as a modified Mayo Score with stool frequency subscore ≤1, rectal bleeding subscore of 0, and endoscopic subscore ≤1) after 8 weeks, compared to 4–5% on placebo. In the maintenance trial, 42% (15 mg) and 52% (30 mg) of patients achieved remission at 52 weeks, versus 12% on placebo, showing a 26% better remission rate at 30 mg compared to 15 mg. Rapid symptom relief was observed as early as 2 weeks, with significant endoscopic improvement (reduced colon inflammation) and corticosteroid-free remission in many patients.

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Velsipity: An S1P Receptor Modulator

Velsipity, developed by Pfizer and approved in October 2023, is an oral S1P receptor modulator that selectively binds to S1P receptor subtypes 1, 4, and 5. Unlike Rinvoq’s intracellular approach, Velsipity works by trapping lymphocytes (immune cells) in lymph nodes, preventing their migration to the colon and reducing inflammation. This mechanism is distinct from biologics or JAK inhibitors, offering an alternative for patients who fail other therapies.

In the ELEVATE UC Phase 3 trials, 26% of patients on 2 mg daily Velsipity achieved clinical remission at 12 weeks, compared to 15% on placebo (p<0.05). At 52 weeks, remission rates increased to 32% versus 7% for placebo. Secondary endpoints, including endoscopic improvement and mucosal healing (disappearance of ulcers), were also met, with results published in The Lancet in March 2023. Velsipity’s oral administration and favorable safety profile make it a compelling option for seniors seeking non-injectable treatments.

Efficacy Comparison and Senior-Specific Benefits

Both Rinvoq and Velsipity are effective for UC, but their remission rates and timelines differ. Rinvoq shows higher remission rates (26–34% at 8 weeks, up to 52% at 52 weeks) compared to Velsipity (26% at 12 weeks, 32% at 52 weeks), particularly at higher maintenance doses (30 mg). Rinvoq’s rapid onset (2 weeks) is advantageous for seniors needing quick symptom relief, while Velsipity’s consistent long-term outcomes suit those prioritizing sustained remission.

Seniors often prefer oral treatments over injections due to ease of use and reduced physical demands. Injectable biologics like infliximab require clinic visits or self-administration, which can be challenging for seniors with arthritis, vision impairment, or limited mobility. Rinvoq and Velsipity’s once-daily pills simplify adherence, improving quality of life. Additionally, oral therapies eliminate the need for infusion-related costs or travel, which is critical for seniors on fixed incomes or in rural areas.

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Risks and Considerations for Seniors

Both medications carry risks, particularly for seniors, due to age-related immune decline and comorbidities. Rinvoq’s FDA boxed warnings highlight serious infections (e.g., pneumonia, herpes zoster), increased mortality in patients 50+ with cardiovascular risk factors (based on tofacitinib studies), major adverse cardiovascular events (MACE), thrombosis, and malignancies like lymphoma. Common side effects (≥5%) include upper respiratory infections, acne, fever, and elevated liver enzymes. A real-world study reported an 85.2% clinical response rate in UC patients after 8 weeks, but infections were more frequent at 30 mg doses.

Velsipity’s risks include bradycardia (slow heart rate), hypertension, and infections, with common side effects (≥5%) like headache, elevated liver tests, and dizziness. Its cardiovascular effects require ECG monitoring before starting treatment, which may be a consideration for seniors with heart conditions. Unlike Rinvoq, Velsipity lacks boxed warnings for mortality or MACE, potentially making it safer for seniors with cardiovascular risk factors, though direct comparisons are limited.

Steps for Starting Treatment Safely

Seniors considering Rinvoq or Velsipity should follow these steps to ensure safe initiation and management:

1. Consult a Specialist: Work with a gastroenterologist to assess UC severity and review medical history, including cardiovascular risk factors, infections, or cancer. Rinvoq is not recommended for seniors over 50 with heart disease risk factors, while Velsipity requires cardiovascular evaluation.

2. Pre-Treatment Screening: Complete blood tests (liver enzymes, blood counts, lipids), tuberculosis (TB) screening, and hepatitis tests. For Velsipity, an ECG is needed to rule out heart rhythm issues. Vaccinations (e.g., shingles, pneumococcal) should be updated before starting either drug, avoiding live vaccines during treatment.

3. Start with Induction Doses: Rinvoq typically begins with 45 mg daily for 8 weeks, followed by 15–30 mg maintenance. Velsipity starts at 2 mg daily without a loading dose. Follow prescribed schedules to optimize efficacy and minimize side effects.

4. Monitor Side Effects: Regular blood tests (every 4–8 weeks initially) are essential to track liver function, blood counts, and lipids. Report symptoms like fever, fatigue, or chest pain immediately. For Velsipity, monitor blood pressure and heart rate regularly.

5. Lifestyle Adjustments: Maintain a low-inflammatory diet, stay hydrated, and avoid smoking, which increases Rinvoq’s risks. Regular exercise, tailored to mobility, can support overall health and UC management.

6. Collaborate with Caregivers: Seniors should involve caregivers or family members to ensure medication adherence and prompt reporting of side effects. AbbVie’s patient support program (AbbVie Contigo) and Pfizer’s resources offer assistance with access and education.

Choosing Between Rinvoq and Velsipity

The choice between Rinvoq and Velsipity depends on individual factors like disease severity, comorbidities, and treatment preferences. Rinvoq’s higher remission rates and rapid onset make it ideal for seniors with severe symptoms, but its safety profile requires stricter monitoring. Velsipity’s lower remission rates are offset by a potentially safer cardiovascular profile, appealing to seniors with heart concerns. Cost is another factor: both drugs are expensive, but manufacturer assistance programs and insurance coverage can reduce out-of-pocket expenses.

Conclusion

Rinvoq and Velsipity represent cutting-edge oral treatments for seniors with moderate to severe UC, offering alternatives to injectable biologics. Rinvoq’s JAK1 inhibition delivers rapid, high remission rates (up to 52% at 30 mg), while Velsipity’s S1P modulation provides consistent long-term outcomes (32% at 52 weeks). Seniors benefit from the convenience of oral administration, which supports adherence and independence. However, both medications require careful monitoring due to risks like infections or cardiovascular effects, particularly in older adults. By following safe initiation steps and working closely with healthcare providers, seniors can leverage these innovative therapies to manage UC effectively, improving symptoms and quality of life in 2025.web:4,9,15