Teenager With Hard-to-Treat Crohn’s Disease Achieves Remission With a Combination of Upadacitinib and Risankizumab

Table of Contents

• Key Points
• Understanding Crohn’s Disease
• How This Case Was Studied
• The Patient’s Journey: 7 Years of Crohn’s Disease
• The Combination Therapy That Turned Things Around
• Results: Remission at 9 Months
• What Current Research Already Shows
• What This Means for Patients and Families
• Study Limitations: What This Case Cannot Prove
• Recommendations for Patients
• Frequently Asked Questions
• Source Information

Key Points

• A 17-year-old with Crohn's refractory to three biologics achieved remission only after adding risankizumab to upadacitinib.
• Remission at 9 months included no symptoms, normal inflammation markers, and healed bowel tissue on colonoscopy and biopsy.
• The patient's earlier ustekinumab and upadacitinib courses produced partial clinical response but left ongoing gut inflammation.
• The combination of upadacitinib and risankizumab is off-label; evidence in adolescents comes from this single case report.
• Combining two drug classes with different mechanisms may be a salvage option to avoid surgery in severe refractory Crohn's disease.

Understanding Crohn’s Disease

Crohn’s disease (CD) is an autoimmune disease of the gastrointestinal tract. “Autoimmune” means the body’s own immune system mistakenly attacks healthy tissue. In Crohn’s disease, that attack causes inflammation, ulcers, and tissue damage in the digestive tract. The disease typically follows a relapsing-remitting pattern — periods of active symptoms alternate with periods of relative quiet.

Any part of the digestive tract can be affected, but the terminal ileum (the last section of the small intestine) and the colon (large intestine) are most commonly involved.

How common is this disease? In North America, the incidence of inflammatory bowel disease (IBD) — the family of conditions that includes Crohn’s disease and ulcerative colitis — varies by region. Ulcerative colitis affects between 2.2 and 19.2 cases per 100,000 person-years. Crohn’s disease ranges from 3.1 to 20.2 cases per 200,000 person-years, as reported in the original article. In plain terms, for every 100,000 to 200,000 people observed for one year, a small number will be newly diagnosed.

Three main factors are thought to drive Crohn’s disease: immune system activation, genetic predisposition (inherited risk), and changes in the gut microbiome (the community of bacteria that lives in the intestines). Together, these lead to breakdown of the intestinal lining.

Crohn’s disease most often begins between ages 20 and 40, with a smaller second peak between ages 50 and 60. The most common symptoms are abdominal pain, fever, and signs of bowel obstruction or diarrhea — which may contain blood, mucus, or both.

There is no single test that diagnoses Crohn’s disease. Instead, doctors combine several evaluations: endoscopy (a camera examination of the bowel), microscopy (testing tissue samples under a microscope), radiology imaging, and laboratory testing.

Once diagnosed, disease activity is classified into remission, mild disease, moderate disease, or severe disease. Doctors often use the Crohn’s Disease Activity Index (CDAI), a scoring system based on symptoms, quality of life, complications, and treatment issues. The score categories are:

• Mild-to-moderate Crohn’s disease: CDAI score 150–220
• Moderate-to-severe Crohn’s disease: CDAI score 220–450
• Severe or fulminant (rapidly worsening) Crohn’s disease: CDAI score above 450

For moderate-to-severe disease, doctors commonly turn to advanced therapies. These include biologics (lab-made antibody drugs that target specific immune proteins) and small molecules (oral drugs that block inflammation pathways inside cells).

Treatment is urgent because the stakes are high. About half of all people with Crohn’s disease will eventually need at least one surgical procedure in their lifetime. Surgeries can include drainage of abscesses (pus collections), laparoscopic or open removal of diseased bowel segments (resection), and strictureplasty (a procedure that widens narrowed sections of bowel). Surgery is challenging, and the approach depends heavily on where the disease sits and how severe it is.

Early biologic treatment can improve outcomes in both children and adults with Crohn’s disease. But not everyone achieves lasting remission. Even with biologics, the risk of surgery remains. When standard biologics fail, treatment options become limited — which is exactly the situation this teenage patient faced.

How This Case Was Studied

This article is a case report: a detailed medical write-up of a single patient’s experience. Case reports cannot prove that a treatment works for everyone. Instead, they document unusual successes or failures in real patients, offering clues that larger studies can later test.

The report was written by two gastroenterologists at the Haya Al-Habib Gastroenterology Center, Mubarak Al-Kabeer Hospital, in Jabriya, Kuwait. They tracked the patient’s course over roughly two years, from December 2022 through late 2024.

The doctors measured disease activity using several tools:

• Clinical symptoms — how many bowel movements per day, whether there was rectal bleeding, and the patient’s overall well-being
• C-reactive protein (CRP) — a blood test that measures general inflammation; normal is usually below 5 mg/L in this context
• Fecal calprotectin — a stool test that measures inflammation directly in the gut; below 150 mcg/g is considered a treatment target
• Hemoglobin — a blood count marker used to detect anemia from chronic intestinal bleeding
• Body mass index (BMI) — a measure of weight relative to height, used to track nutrition status
• Colonoscopy with biopsies — a camera examination of the colon and terminal ileum, with tissue samples taken for microscopic analysis
• The Simple Endoscopic Score for Crohn’s Disease (SES-CD) — a numerical score doctors assign after colonoscopy that grades the size and depth of ulcers, the amount of inflamed surface, and the presence of narrowing; a score below 4 indicates quiescent (inactive) disease

The authors also checked for infection. Tests for Clostridium difficile (a bacteria that causes severe diarrhea) and Cytomegalovirus colitis (a viral infection of the colon) were repeatedly negative. This mattered because infections can mimic or worsen Crohn’s flares. The patient and his parents gave written informed consent for each treatment decision, and the report notes that no financial support or conflicts of interest were declared.

The Patient’s Journey: 7 Years of Crohn’s Disease

The patient was diagnosed with severe Crohn’s disease at age 10. His first treatment was adalimumab (an anti-TNF biologic) plus mesalamine (an anti-inflammatory bowel medication). For years, his disease remained difficult to control.

In December 2022, at age 14, he was referred to the hospital’s adult Gastroenterology Department. At that point, he reported 5 to 6 bowel movements per day, with occasional rectal bleeding. On examination, he had cachexia (severe weight loss and muscle wasting). His hemoglobin level was critically low at 7 g/dL — normal for a teenaged male is roughly 13 to 17 g/dL — reflecting significant chronic blood loss. Infectious testing came back negative for Clostridium difficile and Cytomegalovirus.

Doctors first achieved remission with a tapering course of oral prednisolone (a corticosteroid), starting at 40 mg daily. To maintain that remission, they switched him to infliximab (another anti-TNF biologic) at a standard dose of 5 mg/kg. But in February 2023, after only two doses, he relapsed shortly after the steroid was stopped. The reason: mechanistic failure of infliximab — meaning the drug simply did not control his disease, even though it was working at the right level.

During this relapse, he had diarrhea more than 6 times per day. His CRP level was markedly elevated at 75 mg/L. Importantly, his infliximab blood level was therapeutic (within the effective range), and he had no anti-drug antibodies (the immune system was not attacking the medication). This confirmed that the problem was the drug’s mechanism, not dosing or immunity.

Colonoscopy at that time showed severe ileocolonic Crohn’s disease — inflammation in both the terminal ileum and the colon. The team then tried ustekinumab, a biologic that blocks interleukin-12 and interleukin-23. He received a 260 mg intravenous induction dose and achieved clinical remission. Maintenance was set at 90 mg subcutaneously (under the skin) every 8 weeks.

He improved for a while, but his CRP remained high at 39 mg/L, and he reported occasional rectal bleeding. Doctors intensified the regimen: ustekinumab 90 mg every 4 weeks instead of every 8 weeks. This kept him in clinical remission for 9 months, and his CRP fell to 16 mg/L. He was scheduled for a follow-up gastroscopy and colonoscopy.

In February 2024, his BMI was 17 (underweight), and his hemoglobin was again low at 7.6 g/dL, so he received intravenous (IV) iron therapy. The follow-up colonoscopy revealed the disease was still active despite the intensified ustekinumab: multiple medium-sized deep ulcers with surrounding swelling (edema) and redness (erythema) in the terminal ileum and cecum (the first part of the large intestine), with skip lesions — patches of inflamed bowel separated by stretches of normal bowel. Biopsies confirmed moderately active Crohn’s disease.

Ustekinumab was stopped because the disease was endoscopically active — meaning the camera showed active inflammation even when symptoms were partly controlled. The Surgical Department reviewed the case and offered an ileocolectomy with anastomosis (removal of the diseased ileum and part of the colon, with the healthy ends reconnected). The patient and his parents refused surgery.

At this point, options were running out. The patient had already failed three major classes of advanced treatment: adalimumab, infliximab, and ustekinumab. He had also been dependent on steroids. The care team discussed off-label medical options with the family in detail.

The Combination Therapy That Turned Things Around

The first salvage attempt was upadacitinib, a selective JAK1 inhibitor — a small-molecule drug that blocks Janus kinase 1, an enzyme that acts as an inflammation switch inside immune cells. This drug is approved by the US Food and Drug Administration (FDA) and the European Medicines Agency for Crohn’s disease in adults and in children above age 12. Because the patient was 17, it was an available option.

Doctors ruled out contraindications, obtained written informed consent, and started an induction course of upadacitinib 45 mg daily for 12 weeks. After 3 months, the patient’s fecal calprotectin was 923 mcg/g — a very high level indicating active gut inflammation. This prompted the team to extend the induction period to 24 weeks.

By August 2024 — 6 months after starting upadacitinib — the patient felt clinically well. But his fecal calprotectin was still 500 mcg/g, a level that reflects ongoing inflammation. This was only a partial response. The family asked the team to look for other rescue options.

The decision was made to start advanced combination targeted therapy as an off-label treatment: pairing upadacitinib with risankizumab, an interleukin-23 p19 inhibitor (a biologic antibody that blocks IL-23, a protein that fuels intestinal inflammation). The logic was that the two drugs attack different pathways. Upadacitinib blocks the JAK1 enzyme inside cells; risankizumab neutralizes IL-23 outside cells. Using both, the theory goes, creates a broader attack on the inflammatory process.

Again, written informed consent was obtained from the patient and his parents, explaining the benefits and risks. The regimen was:

• Upadacitinib 45 mg taken orally (by mouth) once daily
• Risankizumab 600 mg given intravenously at week 0, week 4, and week 8 (induction)
• Risankizumab 360 mg given subcutaneously every 8 weeks (maintenance), continuing alongside the daily upadacitinib

Results: Remission at 9 Months

The combination worked quickly. At the 8-week follow-up, the patient’s BMI had risen from 17 to 18. His hemoglobin had recovered to 14.4 g/L. He was symptom-free. His CRP had dropped from elevated levels to just 2.05 mg/L — well within the normal range.

His improvement held over time. He continued in clinical remission, with normal CRP levels and fecal calprotectin within target (below 150). At 9 months on the combination therapy, a repeat colonoscopy showed quiescent (inactive) disease, with a Simple Endoscopic Score for Crohn’s disease (SES-CD) below 4.

The colonoscopy images taken before treatment showed deep ulcers, swelling, redness, and skip lesions in the rectum, ascending colon, terminal ileum, and cecum. Images taken 9 months after combination treatment showed healed, quiet bowel tissue throughout. Tissue biopsies taken before treatment showed typical signs of active Crohn’s disease under the microscope, including:

• Crypt abscesses — collections of white blood cells inside the intestinal glands
• Cryptitis — inflammation within those glands
• Crypt architecture distortion — changes in the normal shape of the intestinal glands from chronic damage
• Paneth cell metaplasia — the appearance of specialized cells in an area where they do not normally belong, a sign of chronic injury

After treatment, no such active inflammation was seen. The report emphasizes that no adverse effects occurred during the combination therapy. Monitoring consisted of close clinical follow-up and routine laboratory testing; no special safety measures beyond that were needed.

One crucial achievement deserves emphasis: the patient avoided surgery. He did not have an ileocolectomy, and his colon was preserved.

What Current Research Already Shows

This case did not emerge from a vacuum. The authors reviewed the existing evidence on these two drugs, both alone and in combination. This context matters because the patient had already failed the standard options.

Why previous treatments failed. Anti-TNF agents (infliximab and adalimumab) are currently the only biologics with FDA approval for treating Crohn’s disease in pediatric patients. When these drugs fail, alternative options include vedolizumab (a gut-selective anti-integrin), ustekinumab, and newer therapies such as risankizumab and upadacitinib. This patient had already tried and failed three of these before the combination therapy.

Evidence for risankizumab.

• Risankizumab is FDA-approved for moderate-to-severe active Crohn’s disease in adults.
• In the phase 3 ADVANCE and MOTIVATE induction trials — which included 1,549 participants aged 16 to 80 — risankizumab outperformed placebo, with remission rates of approximately 40% to 45% in patients who had not responded to other biologics.
• Only 14 adolescents aged 16 to 17 were included in those trials, which limits solid evidence for teenagers.
• A real-world French study (the GETAID study) found that approximately 46% of patients who had been refractory (non-responsive) to anti-TNF therapy, vedolizumab, and ustekinumab achieved steroid-free clinical remission after treatment with risankizumab.
• A preliminary pediatric report, which included children below age 16, showed a clinical remission rate of about 70% after 3 infusions, with no treatment-related adverse effects.

Evidence for upadacitinib.

• Upadacitinib is the first FDA-approved oral medication for moderate and severe Crohn’s disease in adults.
• A post hoc analysis of the U-EXCEL, U-EXCEED, and U-ENDURE phase 3 trials found upadacitinib effective and safe in patients with prior CD-related surgeries, compared with placebo.
• An international multicenter retrospective study that included 100 children (mean age 15.4 years) concluded that upadacitinib was effective and safe in children below age 16.

Evidence for combining biologics.

• Experience from a tertiary care center (a specialized referral hospital) supports combining biologics with different mechanisms of action as safe and effective for managing IBD.
• A systematic review with meta-analysis found that combining vedolizumab with anti-TNF agents produced a clinical response rate of 78% and a remission rate of 55%. That review did not test risankizumab plus upadacitinib specifically, but its results support attacking two different inflammatory pathways at once.
• A descriptive case series of 27 patients aged 16 and older with refractory Crohn’s disease evaluated upadacitinib combined with various biologics, including risankizumab. Among the 17 patients who received upadacitinib plus risankizumab specifically, a clinical response was seen in 9 patients by week 52 (±4 weeks).
• A retrospective study from Taiwan (16 patients, median age 41.5 years) used combination therapy for refractory IBD, most often ustekinumab plus upadacitinib. Remission rates were 50% at week 12 and 80% at week 24.

Why risankizumab over ustekinumab in this case? A head-to-head clinical trial in adults who had not responded to anti-TNF therapy found risankizumab superior to ustekinumab. It produced better remission rates at weeks 24 and 48, and better endoscopic remission at week 48. That evidence influenced the authors’ choice to pair upadacitinib with risankizumab rather than with ustekinumab.

The authors note that most existing combination studies focused on adults, not adolescents. Their case adds a data point for the teenage population.

What This Means for Patients and Families

For a teenager with severe Crohn’s disease who has failed multiple biologics, this case offers a clear, hopeful message: a combination of two newer medications — upadacitinib and risankizumab — can produce complete remission across all three measures that matter: symptoms, laboratory markers, and direct endoscopic visualization of the bowel.

It is especially meaningful that remission was achieved in all three domains. Some treatments improve how patients feel but leave silent inflammation behind — which is exactly what happened with this patient’s earlier ustekinumab and upadacitinib courses. Blood tests may look normal while the colon is still damaged. This case shows that combined therapy was able to heal the tissue, not just quiet the symptoms.

The case also reinforces that surgery is not inevitable, even in severe refractory disease. The patient and his family refused surgery, pursued an aggressive medical option, and preserved his bowel.

For doctors, the lesson is about sequencing. Both upadacitinib and risankizumab have already received regulatory approval as individual drugs. Using them together, however, is currently off-label — meaning not specifically approved as a combination. The authors emphasize shared decision-making. In this case, the risks and benefits were explained, and the family gave written informed consent at every step.

Study Limitations: What This Case Cannot Prove

This is a single-patient case report, not a clinical trial. That comes with important limits that patients should understand.

• No control group. There is no comparison patient who received a placebo or a different treatment. We cannot know for certain that the combination therapy — rather than the earlier months of upadacitinib, natural fluctuations in disease, or other factors — deserves full credit for the remission.
• Partial response before combination. The patient had already been on upadacitinib for 6 months before risankizumab was added. Although his disease was still active (fecal calprotectin 500 mcg/g), it is possible that the upadacitinib had set the stage for the later improvement.
• One patient, one outcome. What worked for this 17-year-old may not work for others. Crohn’s disease varies hugely between individuals.
• Adolescent evidence gap. Major trials like ADVANCE and MOTIVATE included only 14 adolescents. The evidence base for both drugs in teenagers is far thinner than in adults.
• Safety data is limited. No adverse effects occurred in this patient, but one patient cannot establish a safety profile. Both drugs suppress the immune system, and long-term risks (such as infection or malignancy) require study in larger groups over longer time periods.
• Off-label use. The combination is not yet formally approved, and dosing, timing, and monitoring protocols are not standardized.
• Possible publication bias. Case reports tend to highlight successes. Failures or complications from similar combinations may be less likely to be published.

The authors themselves state that while the combination may be a good option for refractory Crohn’s disease, confirming its safety and efficacy in larger clinical trials remains essential.

Recommendations for Patients

If you or your child has Crohn’s disease that is not responding to standard treatments, here are practical steps based on this case and the evidence it reviews:

1. Work with a specialized IBD team. Patients with refractory disease benefit from care at a center with deep experience in biologics, small molecules, and complex treatment decisions.
2. Ask about treat-to-target monitoring. This case shows how important objective targets are. Symptoms alone are not enough. Ask your doctor how your CRP, fecal calprotectin, and endoscopic scores are tracking.
3. Know the difference between response and remission. A partial response (feeling better but calprotectin still elevated) is not the finish line. This patient’s calprotectin of 500 mcg/g on upadacitinib alone was the signal to escalate.
4. Inquire about combination therapy as a salvage option. If multiple biologics have failed and surgery is being discussed, ask whether dual targeted therapy is appropriate in your situation. Discuss the off-label nature, expected benefits, and potential risks openly with your doctor.
5. Address nutrition and anemia. This patient needed IV iron and had a low BMI before treatment improved. Chronic intestinal inflammation and bleeding can rob the body of iron and calories. Supportive care — iron infusions, nutrition support — should run alongside medical therapy.
6. Consider clinical trials. Larger trials are needed to confirm what this case suggests. Trials may offer access to emerging combination strategies with closer monitoring.
7. Get mental and practical support. A 7-year battle with a chronic disease, multiple failed medications, and a surgery recommendation is exhausting. Families facing this path deserve psychological support and time to make shared decisions.

Every treatment decision is a balance between benefit and risk. In this case, the balance tipped strongly toward benefit. The patient achieved what every person with Crohn’s disease hopes for: no symptoms, normal lab results, healed bowel tissue, and no surgery.

Frequently Asked Questions

What is Crohn's disease and how does it affect the body?

Crohn's disease is a chronic autoimmune condition that inflames the digestive tract, often the small intestine and colon. The immune system attacks healthy tissue, causing ulcers and damage. It typically follows a relapsing-remitting pattern. Symptoms include abdominal pain, diarrhea, and rectal bleeding.

What did this case report show about treating refractory Crohn's disease in a teenager?

It described a 17-year-old with severe Crohn's disease who had failed three biologics. Six months of upadacitinib alone gave only partial response. When risankizumab was added, his symptoms disappeared, inflammation markers normalized, and colonoscopy at 9 months showed inactive disease. Surgery was avoided.

What are upadacitinib and risankizumab, and how do they work together?

Upadacitinib is an oral JAK1 inhibitor that blocks inflammation inside cells. Risankizumab is an IL-23 inhibitor biologic that neutralizes a protein fueling gut inflammation. Combining them attacks two different pathways in the inflammatory process. Both are approved individually for Crohn's disease, but not together.

Is the combination of upadacitinib and risankizumab approved for teenagers?

No. Both drugs are approved individually for certain ages—upadacitinib for adults and children above 12, risankizumab for adults. Using them together is off-label. In this case, a 17-year-old received the combination after written informed consent, and it led to remission without adverse effects.

What tests were used to measure whether the treatment worked?

Doctors tracked symptoms, C-reactive protein (CRP) in blood, fecal calprotectin in stool, hemoglobin, BMI, and colonoscopy with biopsies. They also used the Simple Endoscopic Score for Crohn's Disease (SES-CD). Remission meant no symptoms, CRP normal, fecal calprotectin below 150, and SES-CD below 4.

What limitations does this case report have?

This is a single-patient case report, not a clinical trial. There was no control group. The patient had been on upadacitinib for six months before risankizumab was added, so the full credit is uncertain. Evidence for these drugs in adolescents is thin, and long-term safety is not established.

What practical steps should patients and families take if standard treatments fail?

Work with a specialized IBD team, ask about treat-to-target monitoring with CRP and fecal calprotectin, and know the difference between partial response and remission. If multiple biologics have failed, discuss whether dual targeted therapy might be appropriate, including its off-label nature, benefits, and risks.

My teenage son with Crohn's disease failed several biologics and doctors recommend surgery. When should we seek a second opinion about combination therapy like upadacitinib plus risankizumab instead?

If a teenager with Crohn's disease has not responded to multiple biologics and surgery such as ileocolectomy is recommended, a second opinion may help clarify whether combined treatment with upadacitinib and risankizumab is worth considering. In one reported case, a 17-year-old in this exact situation achieved remission and avoided surgery after adding risankizumab to upadacitinib. A colonoscopy at 9 months showed inactive disease. Still, this was a single case and the combination is off-label. A second opinion can review the full history and discuss risks and alternatives. Diagnostic Detectives Network provides independent expert second opinions.

Source Information

Original article title: A 17-Year-Old Male Adolescent With Refractory Crohn’s Disease Managed With Upadacitinib and Risankizumab Combination Therapy

Authors: Mohammad Alhashemi and Mohammad Shehab (Mohammad Abdullah Shehab, corresponding author)

Institution: Haya Al-Habib Gastroenterology Center, Mubarak Al-Kabeer Hospital, Jabriya, Kuwait

Publication details: American Journal of Case Reports (Am J Case Rep), 2026; Volume 27: e950174. e-ISSN 1941-5923. DOI: 10.12659/AJCR.950174. Received June 7, 2025; accepted November 3, 2025; published January 16, 2026.

Funding and conflicts: The authors declared no financial support and no conflicts of interest. Patient informed written consent was obtained.

This patient-friendly article is based on peer-reviewed research published in the American Journal of Case Reports. It is intended to explain the study for non-specialist readers and does not replace individualized advice from a qualified medical professional.