Clinical Insights into Axial Spondyloarthritis: Rheumatology Drugs at a Glance, Part 5

Adalimumab is administered by subcutaneous (SC) injection. The recommended dose is

40 mg every other week.

Commentary: The approval of adalimumab was based on two randomized, multicenter, double-blind, placebo-controlled clinical studies in close to 500 patients who had active axSpA. The results showed the drug was effective in reducing pain and inflammation in axSpA patients after 12 weeks of treatment, meeting the trial’s end point.

Certolizumab pegol (Cimzia):¹¹ injection

Drug class: TNFi

Boxed Warning: Refer to *ISI* (left)

Warnings & Precautions

• Do not start certolizumab pegol during an active infection. If an infection develops, monitor carefully and stop the drug if the infection becomes serious.
• Invasive fungal infections—for patients who develop a systemic illness on certolizumab pegol, consider empiric antifungal therapy for those at high risk who reside in, or travel to, regions where mycoses, such as histoplasmosis, coccidioidomycosis or blastomycosis, are endemic.
• Cases of lymphoma and other malignancies have been observed in patients receiving TNFi’s.
• Heart failure, worsening or new onset, may occur.
• Anaphylaxis or serious allergic reactions may occur.
• HBV reactivation can occur; test for HBV infection before starting certolizumab pegol. Monitor HBV carriers during and several months after therapy. If reactivation occurs, stop the drug and begin antiviral therapy.
• Demyelinating disease, exacerbation or new onset, may occur.
• Cytopenias, pancytopenia—advise patients to seek immediate medical attention if symptoms develop, and consider stopping certolizumab pegol.
• Avoid concomitant use with anakinra, abatacept, rituximab and natalizumab due to an increased risk of serious infections.
• Lupus-like syndrome—stop certolizumab pegol if the syndrome develops.
• Avoid live vaccines.

Dosage & Administration

AxSpA and nr-axSpA: Certolizumab pegol is administered by SC injection. The recommended dose is 400 mg (given as two SC injections of 200 mg each) initially at weeks 2 and 4, followed by 200 mg every other week or 400 mg every four weeks.

Commentary: Certolizumab pegol is the first FDA-approved treatment for nr-axSpA. The efficacy of certolizumab pegol for the treatment of nr-axSpA was studied in a randomized clinical trial of 317 adult patients with nr-axSpA and objective signs of inflammation, indicated by elevated C-reactive protein (CRP) levels and/or sacroiliitis on MRI. Improvement responses were greater for patients treated with certolizumab pegol than patients who received a placebo. The overall safety profile observed in the certolizumab pegol treatment group was consistent with the drug’s known safety profile.

Etanercept (Enbrel):¹² injection

Biosimilars: etanercept-szzs (Erelzi),¹³ etanercept-ykro (Eticovo)¹⁴

Drug class: TNFi

Boxed Warning: Refer to *ISI* (p. 12)

Warnings & Precautions

• Do not start etanercept during an active infection. If an infection develops, monitor carefully and stop etanercept if the infection becomes serious.
• Consider empiric antifungal therapy for patients at high risk (those who reside in, or travel to, regions where mycoses, such as histoplasmosis, coccidioido­mycosis or blastomycosis, are endemic) of invasive fungal infections who develop a severe systemic illness on etanercept.
• Demyelinating disease, exacerbation or new onset, may occur.
• Cases of lymphoma have been observed in patients receiving TNFi’s.
• Congestive heart failure, worsening or new onset, may occur.
• Advise patients to seek immediate medical attention if symptoms of pancytopenia or aplastic anemia develop, and consider stopping etanercept.
• Monitor HBV carriers for reactivation during and following therapy. If reactivation occurs, consider stopping etanercept and beginning antiviral therapy.
• Anaphylaxis or serious allergic reactions may occur.
• Stop etanercept if lupus-like syndrome or autoimmune hepatitis develops.

Dosage & Administration

Etanercept is administered by SC injection. The recommended initial dose is 50 mg once weekly.

Commentary: Etanercept was the first biologic approved by the FDA to reduce the signs and symptoms in patients with axSpA. In a pivotal phase 3 study of 277 patients, 60% of etanercept-treated patients achieved a 20% improvement in the Assessment in Ankylosing Spondylitis Response Criteria (ASAS 20), a composite measure that includes back pain, morning stiffness, inflammation and physical function, compared with 27% of patients receiving placebo, after 12 weeks. The adverse events were similar to those reported in previous clinical trials, with injection site reactions occurring more frequently than in the placebo group.

Golimumab (Simponi):¹⁵ injection

Drug class: TNFi

Boxed Warning: Refer to *ISI* (p. 12)

Warnings & Precautions

• Do not start golimumab during an active infection. If an infection develops, monitor carefully and stop golimumab if the infection becomes serious.
• For patients who develop a systemic illness on golimumab, consider empiric antifungal therapy for those who reside in, or travel to, regions where mycoses, such as histoplasmosis, coccidioido­mycosis or blastomycosis, are endemic.
• HBV many occur. Monitor HBV carriers during and several months after therapy. If reactivation occurs, stop golimumab and begin antiviral therapy.
• The incidence of lymphoma was seen more often than in the general U.S. population. Cases of other malignancies have been observed among patients receiving a TNFi.
• Heart failure, worsening or new onset, may occur. Stop golimumab if new or worsening symptoms occur.
• Demyelinating disease, exacerbation or new onset, may occur.
• Serious systemic hypersensitivity reactions including anaphylaxis may occur.
• Lupus-like syndrome—stop golimumab if the syndrome develops.

Dosage & Administration

Golimumab is administered by SC injection. The recommended dose is 50 mg once a month.

Commentary: The FDA approval of golimumab injection was based on the results of a phase 3 clinical trial that enrolled 356 patients. The most common adverse reactions (>5%) were upper respiratory tract infection, nasopharyngitis and injection site reactions.

Golimumab (Simponi Aria):¹⁶ infusion

Drug class: TNFi

Boxed Warning: Refer to *ISI* (p. 12)

Warnings & Precautions: Refer to *Simponi

Dosage & Administration

Golimumab is administered by intravenous (IV) infusion. The recommended dose is 2 mg/kg over 30 minutes at weeks 0 and 4, then every eight weeks.

Commentary: The FDA approval of golimumab injection for IV use was based on results from two clinical trials that enrolled more than 600 patients. The trial showed the drug significantly improved the signs and symptoms of axSpA. The most common adverse reactions (>5%) were upper respiratory tract infection, nasopharyngitis and injection site reactions.

Infliximab (Remicade):¹⁷ infusion

Biosimilar(s): infliximab-dyyb (Inflectra),¹⁸ infliximab-abda (Renflexis),¹⁹ infliximab‑qbtx (Ixifi)²⁰

Drug class: TNFi

Boxed Warning: Refer to *ISI* (p. 12) and

• Fatal hepatosplenic T cell lymphoma (HSTCL) have been reported in patients treated with TNFi’s, post-marketing. All infliximab cases occurred in inflammatory bowel disease (IBD) patients, who were mostly adolescent or young adult males. All had received azathioprine or 6-mercaptopurine concomitantly with infliximab at, or prior to, diagnosis.

Warnings & Precautions

• Do not give infliximab during an active infection. If an infection develops, monitor carefully and stop infliximab if the infection becomes serious.
• Invasive fungal infections—for patients who develop a systemic illness on infliximab, consider empiric antifungal therapy for those who reside or travel to regions where mycoses, such as histoplasmosis, coccidioidomycosis or blastomycosis, are endemic.
• The incidence of malignancies, including lymphoma, was greater in infliximab treated patients than in controls. Due to the risk of HSTCL, carefully assess the risk/benefit especially in patients with IBD, men and in patients receiving azathioprine or 6-mercaptopurine treatment.
• HBV reactivation can occur. Therefore, test for HBV infection before starting infliximab. Monitor HBV carriers during and several months after therapy. If reactivation occurs, stop infliximab and begin antiviral therapy.
• Hepatotoxicity—rare, severe hepatic reactions, some fatal or necessitating liver transplantation, have occurred. Stop infliximab in the presence of jaundice and/or marked liver enzyme elevations.
• Heart failure, new onset or worsening, may occur.
• Cytopenias—advise patients to seek immediate medical attention if signs and symptoms develop, and consider stopping infliximab.
• Hypersensitivity—serious infusion reactions including anaphylaxis or serum sickness-like reactions may occur.
• Demyelinating disease, exacerbation or new onset, may occur.
• Lupus-like syndrome—stop infliximab if syndrome develops.
• Live vaccines or therapeutic infectious agents should not be given with infliximab.

Dosage & Administration

Infliximab is administered by IV infusion over a period of not less than two hours. The recommended dose is 5 mg/kg infusion at 0, 2 and 6 weeks, then every six weeks.

Commentary: The FDA approved infliximab for treatment of axSpA was based on data from a phase 3 clinical trial that enrolled 279 patients. The most common adverse reactions (≥10%) were infections (e.g., upper respiratory, sinusitis, pharyngitis), infusion-related reactions, headache and abdominal pain.

Ixekizumab (Taltz):²¹ injection

Drug class: IL-17-RA

Warnings & Precautions

• Serious infections have occurred. Instruct patients to seek medical advice if signs or symptoms of clinically important chronic or acute infection occur. If a serious infection develops, discontinue ixekizumab until the infection resolves.
• Evaluate for TB prior to initiating treatment.
• If a serious hypersensitivity reaction occurs, discontinue ixekizumab immediately and initiate appropriate therapy.
• IBD, including exacerbations, occurred during clinical trials. Monitor closely patients who are treated with ixekizumab and have IBD.

Dosage & Administration

Ixekizumab is administered by subcutaneous injection.

• axSpA: The recommended dose is 160 mg (two 80 mg injections) at week 0, followed by 80 mg every four weeks.
• nr-axSpA: The recommended dose is 80 mg injection every four weeks.

Commentary: The FDA approval of ixekizumab for axSpA was based on two randomized, controlled phase 3 clinical trials that included a total of 657 adult patients. The most common adverse reactions (≥1%) were injection-site reactions, upper respiratory tract infections, nausea and tinea infections.

Secukinumab (Cosentyx):²² injection

Drug class: IL-17-RA

Warnings & Precautions

• Serious infections have occurred. Caution should be exercised when considering using secukinumab in patients with a chronic infection or a history of recurrent infection. If a serious infection develops, discontinue the drug until the infection resolves.
• Prior to initiating treatment with secukinumab, evaluate for TB.
• Caution should be exercised when prescribing secukinumab to patients with IBD; cases of IBD were observed in clinical trials.
• If an anaphylactic reaction or other serious hypersensitivity reaction occurs, discontinue secukinumab immediately and initiate appropriate therapy.

Dosage & Administration

Secukinumab is administered by subcutaneous injection. Administer with or without a loading dosage.

axSpA:

• With a loading dosage: 150 mg at weeks 0, 1, 2, 3 and 4, and every four weeks thereafter;
• Without a loading dosage: 150 mg every four weeks;
• If a patient continues to have active axSpA, consider a dosage of 300 mg every four weeks.

nr-axSpA:

• With a loading dosage: 150 mg at weeks 0, 1, 2, 3 and 4, and every four weeks thereafter;
• Without a loading dosage: 150 mg every four weeks.

Commentary: The FDA approval of secukinumab for axSpA was based on four randomized, controlled phase 3 clinical trials that included a total of 1,500 adult patients. The most common adverse reactions (≥1%) were nasopharyngitis, diarrhea and upper respiratory tract infection.

Mary Choy, PharmD, BCGP, FASHP, is a medical writer and editor living in New York City. Dr. Choy is director of pharmacy practice at the New York State Council of Health-system Pharmacists. She is also the coauthor of Healthcare Heroes: The Medical Careers Guide.

References

1. Ward MM, Deodhar A, Gensler LS, et al. 2019 Update of the American College of Rheumatology/Spondylitis Association of America/Spondyloarthritis Research and Treatment Network Recommendations for the Treatment of Ankylosing Spondylitis and Nonradiographic Axial Spondylo­arthritis. Arthritis Rheumatol. 2019 Oct; 71(10):1599–1613.
2. Zhao SS, Pittam B, Harrison NL, et al. Diagnostic delay in axial spondyloarthritis: A systematic review and meta-analysis. Rheumatology (Oxford). 2021 Apr 6;