Rheumatology Drugs at a Glance, Part 1: Psoriatic Arthritis

infliximab-qbtx (Ixifi)¹³

Drug class: DMARD, TNFi

Boxed warning: Refer to *ISI (left) and

• Fatal hepatosplenic T-cell lymphoma (HSTCL) has 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 infection becomes serious.
• Invasive fungal infections have occurred. For patients who develop a systemic illness on infliximab, consider empiric antifungal therapy for those who reside in or travel to regions where mycoses 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 Crohn’s disease (CD) or ulcerative colitis patients, in males, and if receiving azathioprine or 6-mercaptopurine treatment.

• Hepatitis B virus (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 anti-viral therapy.
• Hepatotoxicity—rare severe hepatic reactions, some fatal or necessitating liver transplantation—have occurred. Stop infliximab in cases of jaundice and/or marked liver enzyme elevations.
• Heart failure—new onset or worsening symptoms may occur.
• Cytopenias have occurred. 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 the syndrome develops.
• Live vaccines or therapeutic infectious agents should not be given with infliximab.

Commentary: The FDA approved infliximab for treatment of active PsA based on data from two clinical trials that showed positive results. The most common adverse reactions (≥10%) are infections (e.g., upper respiratory, sinusitis, pharyngitis), infusion-related reactions, headache and abdominal pain.

Adalimumab (Humira):¹⁴ Injection

Biosimilars: adalimumab-atto (Amjevita),¹⁵ adalimumab-adbm (Cyltezo),¹⁶ adalimumab-adaz (Hyrimoz)¹⁷

Drug class: DMARD, TNFi

Boxed warning: Refer to *ISI (left) and

• Fatal hepatosplenic T-cell lymphoma (HSTCL) have occurred postmarketing in adolescent and young adults IBD patients treated with TNFi’s.

Warnings & Precautions

• Do not start adalimumab during an active infection. If an infection develops, monitor carefully, and stop adalimumab if the infection becomes serious.
• Invasive fungal infections—For patients who develop a systemic illness on adalimumab, consider empiric antifungal therapy for those who reside in or travel to regions where mycoses are endemic.
• The incidence of malignancies was greater in adalimumab-treated patients than in controls.
• Anaphylaxis or serious allergic reactions may occur.
• HBV reactivation can occur. Monitor HBV carriers during and for several months after therapy. If reactivation occurs, stop adalimumab and begin anti-viral therapy.
• Demyelinating disease, exacerbation or new onset, may occur.
• Cytopenias, pancytopenia—advise patients to seek immediate medical attention if symptoms develop, and consider stopping adalimumab.
• Heart failure, worsening or new onset, may occur.
• Lupus-like syndrome—stop adalimumab if the syndrome develops.

Commentary: Adalimumab received an expanded indication based on results from a clinical trial of 313 patients with moderate to severe PsA who had an inadequate response to NSAIDs. Patients taking adalimumab experienced significantly less joint damage than patients taking placebo, and nearly 60% of patients achieved an ACR 20 response through Week 24.The most common adverse reactions (≥10%) are infections (e.g., upper respiratory, sinusitis), injection-site reactions, headache and rash.

Certolizumab pegol (Cimzia):¹⁸ Injection

Drug class: TNF inhibitor

Boxed warning: Refer to *ISI (p. 17)

Warnings & Precautions

• Do not start certolizumab during an active infection. If an infection develops, monitor carefully, and stop certolizumab if the infection becomes serious.
• Invasive fungal infections may occur. For patients who develop a systemic illness on certolizumab, consider empiric antifungal therapy for those who reside in or travel to regions where mycoses 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. Monitor HBV carriers during and several months after therapy. If reactivation occurs, stop certolizumab and begin anti-viral therapy.
• Demyelinating disease, exacerbation or new onset, may occur.
• Cytopenias and pancytopenia may develop. Advise patients to seek immediate medical attention if symptoms develop, and consider stopping certolizumab.
• Lupus-like syndrome—stop certolizumab if the syndrome develops.

Commentary: The FDA approval was based on a multi-center, clinical trial, which showed that patients treated with 200 mg certolizumab every other week demonstrated greater reduction in radiographic progression compared with placebo-treated patients at Week 24.The most common adverse reactions (≥7%) are upper respiratory tract infection, rash and urinary tract infection.

Golimumab (Simponi):¹⁹ Injection

Drug class: TNF inhibitor

Boxed warning: Refer to *ISI (p. 17)

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 are endemic.
• HBV many occur. Monitor HBV carriers during and for several months after therapy. If reactivation occurs, stop golimumab and begin anti-viral 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 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.

Commentary: The FDA approval of golimumab is based on results from a clinical trial that demonstrated a higher proportion of patients having significant improvement in the signs and symptoms of PsA. The most common adverse reactions (≥5%) are upper respiratory tract infection and nasopharyngitis.

Abatacept (Orencia):²⁰ Injection/Infusion

Drug class: selective T cell costimulation modulator, DMARD, immunomodulator

Warnings & Precautions

• Concomitant use with a TNF blocker can increase the risk of (serious) infections. Discontinue abatacept if a serious infection occurs.
• Anaphylaxis or anaphylactoid reactions can occur after the first infusion and can be life threatening. Appropriate medical support should be immediately available in the event of a reaction. Post-marketing experience notes at least one case of fatal anaphylaxis following the first abatacept infusion. Following an anaphylactic or other serious allergic reaction, abatacept administration should be stopped immediately, with appropriate therapy instituted. Abatacept should be permanently discontinued.
• Patients with a history of recurrent infections or underlying conditions predisposing them to infections may experience more infections.
• Screen for latent TB prior to initiating therapy. Patients testing positive should be treated prior to initiating abatacept.
• Live vaccines should not be given concurrently or within three months of abatacept discontinuation.
• Based on its mechanism of action, abatacept may blunt the effectiveness of some immunizations.
• Chronic obstructive pulmonary disease (COPD) patients may develop more frequent adverse respiratory events.

Commentary: The FDA approved abatacept based on the results of two randomized, controlled trials that involved nearly 600 adults with long-standing PsA. The most common adverse reactions (≥10%) are headache, upper respiratory tract infection, nasopharyngitis and nausea.

Ustekinumab (Stelara):²¹ Injection

Drug class: monoclonal antibody, interleukin (IL-12/23) inhibitor

Warnings & Precautions

• Serious infections have occurred. Do not start ustekinumab during any clinically important active infection. If a serious infection or clinically significant infection develops, consider discontinuing ustekinumab until the infection resolves.
• Theoretical infection risk—Serious infections from mycobacteria, salmonella and Bacillus Calmette-Guerin (BCG) vaccinations have occurred in patients genetically deficient in IL-12/23. Diagnostic tests for these infections should be considered as dictated by clinical circumstances.
• Evaluate patients for TB prior to initiating treatment with ustekinumab. Initiate treatment of latent TB before administering ustekinumab.
• Ustekinumab may increase malignancy risk. The safety of using ustekinumab in patients with a history of, or a known, malignancy has not been evaluated.
• Anaphylaxis or other clinically significant hypersensitivity reactions may occur.
• Reversible posterior leukoencephalo­pathy syndrome (RPLS) has been reported in one case. If suspected, treat promptly and discontinue ustekinumab.
• Cases of noninfectious, interstitial pneumonia, eosinophilic pneumonia and cryptogenic organizing pneumonia have been reported during post-