Real-world experience and long-term outcomes of a mandatory nonmedical switch of adalimumab originator to biosimilars in inflammatory bowel disease

BACKGROUND Over the last decade,the treatment options for inflammatory bowel disease(IBD)have significantly progressed with the emergence of new medications designed to target various immune pathways and mitigate inflammation.Adalimumab(ADA)is a tumor necrosis factor alpha antagonist and stands as an effective treatment for IBD.In April 2021,the province of British Columbia implemented a mandatory non-medical switch policy of the ADA originator Humira®to ADA biosimilars.Biosimilars offer a potential cost-effective,safe,and efficacious alternative to the originator,yet there remains limited real-world evidence on long-term outcomes of ADA non-medical switching in IBD.AIM To assess the long-term outcomes of non-medical switching from the ADA originator Humira®to an ADA biosimilar among IBD patients.METHODS A retrospective observational chart review study was conducted on IBD patients eligible for the provincially mandated non-medical switch to an ADA biosimilar.The primary outcome was treatment persistence at 30 months post-switch.Secondary outcomes included the proportion of and reasons for therapy alteration or ADA discontinuation,loss of response(LOR)rates,adverse events(AE),and clinical and biochemical remission status.Patients who remained on the originator throughout the switch period,through compassionate support or private pay,constituted the comparison group.RESULTS Patients in the originator(n=43)and biosimilar switch(n=228)groups displayed similar demographics and baseline disease characteristics.By the study endpoint of 30 months,there was no difference in the rate of treatment persistence in either group(n=36,83.7%originator group vs n=201,88.2%biosimilar group,P=0.451).Treatment persistence demonstrated similar rates of discontinuation between both study groups(log-rank P=0.543).There was a numerical but not statistically significant difference in rates of adverse outcomes between either group(39.5%originator vs 28.9%biosimilars,P=0.206).This included comparable rates of LOR(27.9%vs 17.5%)or AE(11.6%vs 11.4%)between the originator and biosimilar cohorts,respectively.C-reactive protein and fecal calprotectin levels were similar one year pre-and post-switch.CONCLUSION These data support the long-term efficacy and safety of non-medical ADA switching in IBD and will help inform patients and physicians in jurisdictions currently undergoing biosimilar switching.

Intestinal Behet's disease appearing during treatment with adalimumab in a patient with ankylosing spondylitis

Behet’s disease(BD)is a chronic inflammatory disease affecting multiple organ systems,such as the skin,joints,blood vessels,central nervous system,and gastrointestinal tract.Intestinal BD is characterized by intestinal ulcerations and gastrointestinal symptoms.The medical treatment of intestinal BD includes corticosteroids and immunosupressants.There have been several reports of tumor necrosis factor-α (TNF-α)blockers being successful in treatment of refractory intestinal BD.Here,we report on a patient who was diagnosed with intestinal BD despite treatment with the fully humanized TNF-α blocker(adalimumab)for underlying ankylosing spondylitis.This patient achieved clinical remission and complete mucosal healing through the addition of a steroid and azathioprine to the adalimumab regimen.

Successful use of adalimumab for treating fistulizing Crohn's disease with pyoderma gangrenosum:Two birds with one stone

Crohn＇s disease （CD） is a chronic relapsing and remitting autoinflammatory disorder of the gastrointestinal tract that has many intestinal and extraintestinal complications. The purpose of treatment is long-term remission, reduction of complications, and improvement of patients＇ quality of life. In many cases, this can be quite challenging and it is necessary to have a well thought out management strategy. We present the case of a 38-year-old woman with fistulizing CD that manifested as diffuse abdominal pain and bloody diarrhea accompanied by arthralgia. In addition, there were ulcerative lesions surrounded by cutaneous inflammation and erythema on her extremities, indicative of pyoderma gangrenosum. The patient was treated with high doses of parenteral methylprednisolone without any improvement and was started on adalimumab. A positive response to adalimumab therapy was observed： after 2 mo of therapy, the ulcerative skin lesion healed completely and the enterogastric fistula was closed affcer 5 mo adalimumab treatment. Adalimumab might be a suitable initial as well as maintenance therapy in patients with complicated CD.

A 10-Year Saudi Experience of Using Adalimumab in Treating Juvenile Idiopathic Arthritis

Background: Traditionally, management of Juvenile Idiopathic Arthritis (JIA) involves use of non-steroidal anti-inflammatory drugs (NSAIDS) or disease-modifying anti-rheumatic drugs (DMARDs), such as methotrexate (MTX) or sulfasalazine;or steroids. However, in several cases, a low therapeutic response or important side effects is encountered. This study reports our experience in using adalimumab in JIA patients by assessing the efficacy and safety of this treatment in this category of patients. Methods: A retrospective study was conducted among 38 patients with JIA at the Pediatric Department, King Abdulaziz Univesrity Hospital, Jeddah, Saudi Arabia, in the period January 2005-March 2016. Patients’ records were reviewed and relevant demographic and clinical data were collected. Data were analyzed using SPSS version 21 and represented using tables. Results: The 38 patients were distributed as 11 (28.9%) males and 27 (71.1%) females;mean ± SD age was 11.91 ± 4.54 (range = 3 - 19) years. Mean ± SD (range) disease duration was 3.26 ± 2.52 (0 - 12) years and most frequent diagnoses included polyarticular rheumatoid factor (RF) negative form 12 (31.6%), followed by systemic and oligoarticular JIA with 9 (23.7%) cases each. Before adalimumab, fever was present in 13 (34.2%) cases, followed by rash in 8 (21.0%) cases;while 21 (55.3%) were asymptomatic. Thirty-one (81.6%) were in failure of MTX, 19 (50%) of steroids, 7 (18.4%) of NSAIDS and 3 (7.9%) had had intraarticular injections. Biologically, ANA, RF and anti-CCP were positive in 22 (57.9%), 8 (21.1%) and 4 (10.5%) of the cases, respectively. Uveitis was present in 11 (28.9%) of the patients. Analysis of adalimumab efficacy showed 10 (52.6%) cases of complete remission, 9 (23.7%) of partial remission and 9 (23.7%) other where treatment was discontinued. Major adverse effects included local pain (4 [10.5%]), new onset uveitis (1 [2.6%]) and rash (1 [2.6%]), responsible of 1case of treatment discontinuation. Predictors for complete remission on adalimumab were oligoarticular form (β = 3.450, p = 0.009) and negative RF (β = 2.381, p = 0.036);while predictors for nonresponse, whether complete or partial, were polyarticular form (β = ?3.784, p = 0.005) and positive anti-CCP (β = ?3.178, p = 0.021). Conclusion: Adalimumab is an efficient and relatively safe alternative in the treatment of JIA with relatively high remission rates and lower rates of adverse effects. Further multicentre experiences are warranted to prove its efficacy and safety in the Saudi patients.

Adalimumab induction therapy for ulcerative colitis with intolerance or lost response to infliximab: An open-label study

AIM: To evaluate the efficacy of adalimumab induction therapy in patients with ulcerative colitis who previously responded to infliximab and then lost response or became intolerant. METHODS: Ten patients with ulcerative colitis were enrolled in a 4-wk open-label trial. The patients received a loading dose of 160 mg adalimumab at wk 0 followed by 80 mg at wk 2. The primary efficacy measure was clinical improvement at wk 4, as defined by a decrease in clinical activity index (CAI) of more than 4. RESULTS: Four of 10 patients (40%) benefited from subsequent adalimumab therapy; one patient achieved remission (CAI < 4) and 3 had clinical improvement at wk 4. 6 patients had no response (60%); 2 of 6 (33.3%) subsequently underwent colectomy. This was accompanied by a decrease in median CRP concentration from 16.8 mg/mL at baseline to 3.85 mg/mL at wk 4, excluding two patients who underwent colectomy after two infusions of adalimumab. Among the 6 patients with severe colitis (CAI > 12) at baseline, none achieved remission and only one patient had clinical improvement at wk 4. CONCLUSION: The small advantage of adalimumab in patients with mild to moderate ulcerative colitis and lost response or intolerance to infliximab needs to be confirmed in randomised, double-blind, placebo- controlled trials.

Stevens-Johnson syndrome complicating adalimumab therapy in Crohn's disease

The anti-tumor necrosis factor(TNF)αmedications demonstrate efficacy in the induction of remission and its maintenance in numerous chronic inflammatory conditions.With the increasing number of patients receiving anti-TNFαagents,however,less common adverse reactions will occur.Cutaneous eruptions complicating treatment with an anti-TNFαagent are not uncommon,occurring in around 20%of patients. Adalimumab,a fully humanized antibody against TNFα, may be expected to cause minimal immune-mediated skin reactions compared to the chimeric monoclonal antibody,infliximab.We,however,report a case of Stevens-Johnson syndrome that required hospitalization and cessation of adalimumab in a patient with Crohn’ s disease(CD).In this case report,a 29-year-old male with colonic and perianal CD with associated erythema nodosum and large joint arthropathy developed severe mucositis,peripheral rash and desquamation,fevers and respiratory symptoms concomitant with a second dose of 40 mg adalimumab after a 2 mo break from adalimumab therapy.Skin biopsies of the abdominal wall confirmed erythema multiforme and the patient was on no other drugs and infective etiologies were excluded.The patient responded rapidly to IV hydrocortisone and was able to be commenced on infliximab without recurrence of the Stevens-Johnson syndrome.Desquamating skin reactions have now been described in three of the TNFαantagonists(infliximab,etanercept and adalimumab).These reactions can be serious and prescribers need to be aware of the potential mucocutaneous side effects of these agents,especially as Stevens-Johnson syndrome is associated with significant morbidity and mortality.

Adalimumab-induced interstitial pneumonia in a patient with Crohn's disease

There are several reports of anti-tumor necrosis factor(TNF)-induced lung disease,especially in patients with rheumatologic diseases.Adalimumab is an antiTNF drug used to induce and maintain remission in patients with immune-mediated diseases,such as Crohn’s disease.Although pulmonary disorders could be an extra-intestinal manifestation of inflammatory bowel disease,biologic therapy could also be a cause of lung injury.Only few cases of adalimumab-induced lung toxicity have been reported,and the majority of them were in patients with rheumatologic diseases.Lung injury secondary to anti-TNF therapy should,after ruling out other etiologies,be considered in patients who have a temporal association between the onset of respiratory symptoms and the exposure to these drugs.A compatible pattern in the biopsy and the clinical improvement after discontinuation of the anti-TNF drug would strongly support the diagnosis.

Severe cholestasis due to adalimumab in a Crohn's disease patient

Elevation of liver biochemistry has been reported with anti-tumor necrosis factor agents, but overt liver failure rarely reported. Autoimmune hepatitis has been more commonly reported with infliximab than adalimumab(ADA). Our case, however, describes the first reported case of ADA-associated severe cholestatic injury. A 39-year-old female with Crohn's disease developed severe jaundice after initiation of ADA. All serologic tests and imaging studies were normal. Liver biopsy showed prominent pericentral canalicular cholestasis,without features of steatosis or sclerosing cholangitis,consistent with drug-induced cholestasis. The serum total bilirubin peaked at 280 μmol/L, and improvement was seen after 5 wk with eventual normalization of liver enzymes at 10 wk. Our case describes the first reported case of ADA-associated severe cholestatic liver disease and the first histopathologic examination of this adverse drug effect. Clinicians need to be aware of this potential drug-induced liver injury when prescribing this commonly used biologic medication.

Pyloric stenosis associated Crohn's disease responding to adalimumab therapy

Gastroduodenal Crohn’s disease (CD) is rare and the response to standard medical therapy is often poor. Anti-tumor necrosis factor therapy has revolutionised the treatment of CD. We present a patient with pyloric stenosis associated with CD which improved with Adalimumab therapy. We recommend considering antitumor necrosis factor therapy in symptomatic gastroduodenal CD.

Henoch-Schnlein purpura complicating adalimumab therapy for Crohn's disease

Anti-tumour necrosis factor-α(TNF) therapy has revolutionised the management of chronic inflammatory conditions.With ever increasing numbers of patients being treated with these agents,uncommon adverse reactions will inevitably occur more frequently.Cutaneous manifestations are associated with many of these chronic conditions and can complicate anti-TNF therapy in about 20% of cases.Vasculitic complications are rarely associated with anti-TNF therapy.Henoch-Schnlein purpura(HSP),a small vessel vasculitis,has been described following infliximab and etanercept therapy but never with adalimumab,a fully humanized TNF antibody.The risk of such immune-mediated reactions is theoretically less with adalimumab compared to infliximab but can still occur.Here we report the f irst case in the literature of HSP that can be attributed to the use of adalimumab in a 19-year-old male with recalcitrant Crohn's disease.

Effectiveness of infliximab after adalimumab failure in Crohn's disease

AIM:To evaluate the effectiveness of infliximab as a second-line therapy in Crohn's disease patients after adalimumab failure. METHODS:A historical cohort study in a community-based gastroenterology practice evaluated Crohn's disease patients treated with infliximab (induction plus maintenance) after adalimumab failure. Patients were identified using a large Spanish database (ENEIDA). RESULTS:We included 15 Crohn's disease patients who received infliximab after adalimumab failure. Five patients discontinued adalimumab due to loss of response, 3 due to adverse events and 7 due to partial response. After infliximab therapy was started, all patients who had interrupted adalimumab due to loss of efficacy regained response. All patients who discontinued adalimumab due to adverse events responded to infliximab and maintained this response; one of these patients had an uneventful course on infliximab, but 2 developed adverse events. None of the 7 patients who interrupted adalimumab due to partial response reached remission with infliximab. CONCLUSION:Switching from adalimumab to infliximab may be useful in patients who develop adverse effects or loss of response, however, the benefit of infliximab in primary nonresponders was not established.

Relationship between clinical remission of perianal fistulas in Crohn’s disease and serum adalimumab concentrations:A multicenter cross-sectional study

BACKGROUND Crohn’s disease(CD)is complicated by perianal fistulas in approximately 20%of patients.Achieving permanent fistula closure remains a challenge for physicians.An association between serum anti-tumor necrosis factor-αconcentrations and clinical outcomes in patients with CD has been demonstrated;however,little information is available on serum adalimumab(ADA)concentrations and remission of perianal fistulas in such patients.AIM To study the relationship between serum ADA concentrations and clinical remission of CDassociated perianal fistulas.METHODS This cross-sectional study of patients with CD-associated perianal fistulas treated with ADA was performed at four French hospitals between December 2013 and March 2018.At the time of each serum ADA concentration measurement,we collected information about the patients and their fistulas.The primary study endpoint was clinical remission of fistulas defined as the absence of drainage(in accordance with Present’s criteria),with a PDAI≤4,absence of a seton and assessment of the overall evaluation as favorable by the proctologist at the relevant center.We also assessed fistula healing[defined as being in clinical and radiological(magnetic resonance imaging,MRI)remission]and adverse events.RESULTS The study cohort comprised 34 patients who underwent 56 evaluations(patients had between one and four evaluations).Fifteen patients had clinical remissions(44%),four of whom had healed fistulas on MRI.Serum ADA concentrations were significantly higher at evaluations in which clinical remission was identified than at evaluations in which it was not[14(10-16)vs 10(2-15)μg/mL,P=0.01].Serum ADA concentrations were comparable at the times of evaluation of patients with and without healed fistulas[11(7-14)vs 10(4-16)μg/mL,P=0.69].The adverse event rate did not differ between different serum ADA concentrations.CONCLUSION We found a significant association between high serum ADA concentrations and clinical remission of CD-associated perianal fistulas.

Tislelizumab-related enteritis successfully treated with adalimumab:A case report

BACKGROUND With programmed death-1(PD-1) inhibitors becoming the standard treatment for lung cancer,PD-1-related adverse reactions and treatment have gradually become prominent.CASE SUMMARY First reported case of tislelizumab-related enteritis successfully treated with adalimumab 40mg every 2 wk for 3 times in an advanced lung cancer patient who received first-line tislelizumab/pemetrexed/carboplatin for 4 cycles.The patient continued receiving the treatment of pemetrexed/carboplatin after symptoms,abdominal computed tomography and colonoscopy improved,significant diarrhea was not occurred.CONCLUSION Adalimumab can be an effective treatment option for patients with PD-1 antibody related enteritis if they do not respond well to glucocorticoid treatment.

Adalimumab in prevention of postoperative recurrence of Crohn's disease in high-risk patients

AIM:To evaluate the effectiveness of adalimumab in preventing recurrence after intestinal resection for Crohn's disease in high-risk patients.METHODS:A multicenter,prospective,observational study was conducted from June 2009 until June 2010.We consecutively included high-risk Crohn's disease patients who had undergone an ileal/ileocolonic resection.High-risk patients were defined as two or more criteria:smokers,penetrating pattern,one or more previous surgical resections or prior extensive resection.Subcutaneous adalimumab was administered 2 wk(± 5 d) after surgery at a dose of 40 mg eow,with an initial induction dose of 160/80 mg at weeks 0 and 2.Demographic data,previous and concomitant treatments(antibiotics,5-aminosalicylates,corticosteroids,immunomodulators or biologic therapies),smoking status at the time of diagnosis and after the index operation and number of previous resections(type and reason for surgery) were all recorded.Biological status was assessed with C-reactive protein,erythrocyte sedimentation rate and fecal calprotectin.One year(± 3 mo) after surgery,an ileocolonoscopy and/or magnetic resonance enterography was performed.Endoscopic recurrence was defined as Rutgeerts score ≥ i2.Morphological recurrence was based on magnetic resonance(MR) score ≥ MR1.RESULTS:Twenty-nine patients(55.2% males,48.3% smokers at diagnosis and 13.8% after the index operation),mean age 42.3 years and mean duration of the disease 13.8 years were included in the study.A mean of 1.76(range:1-4) resections previous to adalimumab administration and in 37.9% was considered extensive resection.51.7% had previously received infliximab.Immunomodulators were given concomitantly to 17.2% of patients.Four of the 29(13.7%) developed clinical recurrence,6/29(20.7%) endoscopic recurrence and 7/19(36.8%) morphological recurrence after 1-year.All patients with clinical recurrence showed endoscopic and morphological recurrence.A high degree of concordance was found between clinical-endoscopic recurrence(k = 0.76,P < 0.001) and clinical-morphological recurrence(k = 0.63,P = 0.003).Correlation between endoscopic and radiological findings was good(comparing the 5-point Rutgeerts score with the 4-point MR score,a score of i4 was classified as MR3,i3 as MR2,and i2-i1 as MR1)(P < 0.001,r s = 0.825).During follow-up,five(17.2%) patients needed adalimumab dose intensification(40 mg/wk);Mean time to intensification after the introduction of adalimumab treatment was 8 mo(range:5 to 11 mo).In three cases(10.3%),a biological change was needed due to a worsening of the disease after the dose intensification to 40 mg/wk.One patient suffered an adverse event.CONCLUSION:Adalimumab seems to be effective and safe in preventing postoperative recurrence in a selected group of patients who had undergone an intestinal resection for their CD.

Clinical effects of adalimumab treatment with concomitant azathioprine in Japanese Crohn's disease patients

AIM:To assess adalimumab's efficacy with concomitant azathioprine (AZA) for induction and maintenance of clinical remission in Japanese Crohn's disease (CD) patients. METHODS:This retrospective, observational, singlecenter study enrolled 28 consecutive CD patients treated with adalimumab (ADA). Mean age and mean disease duration were 38.1 ± 11.8 years and 11.8 ± 10.1 years, respectively. The baseline mean Crohn's disease activity index (CDAI) and C-reactive protein were 177.8 ± 82.0 and 0.70 ± 0.83 mg/dL, respectively. Twelve of these patients also received a concomitant stable dose of AZA. ADA was subcutaneously administered:160 mg at week 0, 80 mg at week 2, followed by 40 mg every other week. Clinical response and remission rates were assessed via CDAI and C-reactive protein for 24 wk. RESULTS:The mean CDAI at weeks 2, 4, 8, and 24 was 124.4, 120.2, 123.6, and 135.1, respectively. The CDAI was significantly decreased at weeks 2 and 4 with ADA and was significantly suppressed at 24 wk with ADA/AZA. Overall clinical remission rates at weeks 4 and 24 were 66.7% and 63.2%, respectively. Although no statistically significant difference in C-reactive protein was demonstrated, ADA with AZA resulted in a greater statistically significant improvement in CDAI at 24 wk, compared to ADA alone. CONCLUSION:Scheduled ADA with concomitant AZA may be more effective for clinical remission achievement at 24 wk in Japanese Crohn's disease patients.

Adalimumab in ulcerative colitis: Two cases of mucosal healing and clinical response at two years

Infliximab (IFX) is currently the only biologic therapy used in the treatment of moderate-to-severe ulcerative colitis (UC). In the years to come, more biologic therapies will have a role in the management of moderate-to-severe UC. We report on two patients with steroid-dependent UC who, due to adverse reactions to IFX, have been under therapy with adalimumab for two years. Both patients received concomitant immunosuppressive treatment. Long term clinical remission and mucosal healing are described.

Impact of adalimumab on disease burden in moderate-to-severe ulcerative colitis patients: The one-year, real-world UCanADA study

BACKGROUND A gap remains in documenting the impact of anti-tumor necrosis factor therapy on disease burden in ulcerative colitis(UC)patients treated in a real-world setting.The use of patient-reported outcomes(PROs)has been discussed as a primary endpoint in the context of the FDA PRO Guidance,for labelling purposes.Specifically,the efficacy and safety of adalimumab have been demonstrated in pivotal trials;however,data are needed to understand how clinical results translate into improvements in key aspects of the daily lives of UC patients,such as symptoms,health-related quality of life(HRQoL),and disability.AIM To assess real-world effectiveness of adalimumab on PRO measures in patients with moderate-to-severe UC.METHODS UCanADA was a single arm,prospective,1-year multicenter Canadian post-marketing observational study in which multiple PRO questionnaires were completed—with psychologic distress/depression symptoms as the primary endpoint—by patients with moderate-to-severe UC.Assessments were performed during patients’routine care visit schedule,which was at the initiation of adalimumab(baseline),after induction(approximately 8 wk),and 52 wk after baseline.Additional optional assessments between weeks 8 and 52 were collected at least once but no more than two times during this period.Serious safety events and per-protocol adverse events were collected.RESULTS From 23 Canadian centres,100 patients were enrolled and 48 completed the study.Measured with the Patient Health Questionnaire–9 items at week 52,61.5%(40/65)[95%confidence interval(CI):49.7%-73.4%]of the patients improved in psychologic distress/depression symptoms,which was slightly higher in completers[65.9%(29/44);95%CI:51.9%-79.9%].At week 52,clinical response and clinical remission were achieved respectively by 65.7%(44/73)and 47.8%(32/73)of the patients.The odds of improving depressive symptoms for those achieving a clinical remission at week 52 was 7.94 higher compared with those not achieving a clinical remission(CI:1.42,44.41;P=0.018).Significant changes from baseline to weeks 8 and 52 were observed in disability,HRQoL,and fatigue.Meaningful improvement was reported in work impairment.CONCLUSION At week 52,over 60%of the UCanADA patients had depressive symptoms significantly reduced,as well as HRQoL,fatigue symptoms,and work impairment improved.No new safety signals were detected.

Infliximab vs adalimumab:Points to consider when selecting antitumor necrosis factor agents in pediatric patients with Crohn’s disease

Biologic agents with various mechanisms against Crohn’s disease(CD)have been released and are widely used in clinical practice.However,two anti-tumor necrosis factor(TNF)agents,infliximab(IFX)and adalimumab(ADL),are the only biologic agents approved by the Food and Drug Administration for pediatric CD currently.Therefore,in pediatric CD,the choice of biologic agents should be made more carefully to achieve the therapeutic goal.There are currently no headto-head trials of biologic agents in pediatric or adult CD.There is a lack of accumulated data for pediatric CD,which requires the extrapolation of adult data for the positioning of biologics in pediatric CD.From a pharmacokinetic point of view,IFX is more advantageous than ADL when the inflammatory burden is high,and ADL is expected to be advantageous over IFX in sustaining remission in the maintenance phase.Additionally,we reviewed the safety profile,immunogenicity,preference,and compliance between IFX and ADL and provide practical insights into the choice of anti-TNF therapy in pediatric CD.Careful evaluation of clinical indications and disease behavior is essential when prescribing anti-TNF agents.In addition,factors such as the efficacy of induction and maintenance of remission,safety profile,immunogenicity,patient preference,and compliance play an important role in evaluating and selecting treatment options.

Efficacy and safety of adalimumab in comparison to infliximab for Crohn's disease:A systematic review and meta-analysis

BACKGROUND Adalimumab(ADA)and infliximab(IFX)are the cornerstones of the treatment of Crohn’s disease(CD).It remains controversial whether there is a difference in the effectiveness and safety between IFX and ADA for CD.AIM To perform a meta-analysis to compare the effectiveness and safety of ADA and IFX in CD.METHODS Pub Med,Embase,Cochrane Library,and Web of Science databases were searched.Cohort studies were considered for inclusion.The primary outcomes were induction of response and remission,maintenance of response and remission,and secondary loss of response.Adverse events were secondary outcomes.RESULTS Fourteen cohort studies were included.There was no apparent difference between the two agents in the induction response[odds ratio(OR):1.27,95%confidence interval(CI):0.93-1.74,P=0.14]and remission(OR:1.11,95%CI:0.78–1.57,P=0.57),maintenance response(OR:1.08,95%CI:0.76–1.53,P=0.67)and remission(OR:1.26,95%CI:0.87–1.82,P=0.22),and secondary loss of response(OR:1.01,95%CI:0.65–1.55,P=0.97).Subgroup analysis revealed ADA and IFX had similar rates of response,remission,and loss of response either in anti-tumor necrosis factor-αna?ve or non-na?ve patients.Further,there was a similar result regardless of whether CD patients were treated with optimized therapy,including dose intensification,shortening interval,and combination immunomodulators.However,ADA had a fewer overall adverse events than IFX(OR:0.62,95%CI:0.42–0.91,P=0.02).CONCLUSION ADA and IFX have similar clinical benefits for anti-tumor necrosis factor-αna?ve or non-na?ve CD patients.Overall adverse events rate is higher in patients in the IFX group.

Dose escalation of adalimumab as a strategy to overcome anti-drug antibodies:A case report of infantile-onset inflammatory bowel disease

BACKGROUND Treatment of infantile-onset inflammatory bowel disease(IO-IBD)is often challenging due to its aggressive disease course and failure of standard therapies with a need for biologics.Secondary loss of response is frequently caused by the production of anti-drug antibodies,a well-known problem in IBD patients on biologic treatment.We present a case of IO-IBD treated with therapeutic drug monitoring(TDM)-guided high-dose anti-tumor necrosis factor therapy,in which dose escalation monitoring was used as a strategy to overcome anti-drug antibodies.CASE SUMMARY A 5-mo-old boy presented with a history of persistent hematochezia from the 10th d of life,as well as relapsing perianal abscess and growth failure.Hypoalbuminemia,anemia,and elevated inflammatory markers were also present.Endoscopic assessment revealed skip lesions with deep colic ulcerations,inflammatory anal sub-stenosis,and deep fissures with persistent abscess.A diagnosis of IO-IBD Crohn-like was made.The patient was initially treated with oral steroids and fistulotomy.After the perianal abscess healed,adalimumab(ADA)was administered with concomitant gradual tapering of steroids.Clinical and biochemical steroid-free remission was achieved with good trough levels.After 3 mo,antibodies to ADA(ATA)were found with undetectable trough levels;therefore,we optimized the therapy schedule,first administering 10 mg weekly and subsequently up to 20 mg weekly(2.8 mg/kg/dose).After 2 mo of high-dose treatment,ATA disappeared,with concomitant high trough levels and stable clinical and biochemical remission of the disease.CONCLUSION TDM-guided high-dose ADA treatment as a monotherapy overcame ATA production.This strategy could be a good alternative to combination therapy,especially in very young patients.